DESENVOLVIMENTO EMBRIONÁRIO E DIFERENCIAÇÃO SEXUAL -/- E. I. C. da Silva Departamento de Agropecuária – IFPE Campus Belo Jardim Departamento de Zootecnia – UFRPE sede -/- 1.1 INTRODUÇÃO O sexo foi definido como a soma das diferenças morfológicas, fisiológicas e psicológicas que distinguem o macho da fêmea permitindo a reprodução sexual e assegurando a continuidade das espécies. Os processos de diferenciação sexual são realizados durante o desenvolvimento embrionário, onde ocorre a proliferação, diferenciação e maturação das células germinativas e primordiais, precursoras (...) de ovócitos e espermatozoides em fêmeas e machos, respectivamente. Assim, os embriões machos e fêmeas iniciam o seu desenvolvimento de forma semelhante, de modo que em ambos os sexos se estabelecem em estruturas idênticas a partir das quais se formarão os órgãos reprodutores correspondentes a cada sexo. O conhecimento da origem e do desenvolvimento do aparelho genital é indispensável para entender sua função e as alterações que produzem infertilidade ou esterilidade. 1.2 DETERMINAÇÃO DO SEXO CROMOSSÔMICO Nos mamíferos, o sexo cromossômico é determinado no momento da fertilização, quando um óvulo, que contém um cromossomo X, é fecundado por um espermatozoide portador de um cromossomo X ou um cromossomo Y. No primeiro caso, o complemento cromossômico seria XX, o que originaria uma fêmea (sexo homogamético), e no segundo daria como resultado um macho com a fórmula cromossômica XY (sexo heterogâmico). 1.3 A GÔNADA INDIFERENCIADA A primeira manifestação das gônadas se aprecia no embrião em forma de um par de eminências longitudinais chamadas cristas ou dobras gonodais, situadas em ambos os lados da linha média entre os mesonefros (rins em desenvolvimento) e do mesentério dorsal. Nos embriões dos mamíferos, as células germinativas primordiais (CGP) manifestam-se em estágios precoces do desenvolvimento, podendo ser detectadas pela primeira vez na metade da gastrulação. As CGP são células grandes, de citoplasma claro e núcleo grande e redondo, localizadas na parede do saco vitelino, perto do alantoide. Essas células possuem grande capacidade de proliferação e vão migrar desde o endoderma do intestino e o epitélio do saco vitelino, através do mesentério, até as cristas gonodais. Isso ocorre por volta do 26° dia da gestação no bovino. Sua migração realiza-se graças aos movimentos de translocação passiva e deslocamento ameboide ativo. Desconhece-se o mecanismo pelo qual estas células são dirigidas para as cristas gonodais, porém foram estudadas algumas moléculas que se expressam durante sua migração e que poderiam desempenhar um papel importante na diferenciação deste tipo celular. A fosfatase alcalina é uma enzima que tem sido usada como marcador de CGP para determinar a sua origem e migração. Num estudo recente, foi inserido um marcador fluorescente que se exprime unicamente nas células germinativas primordiais de embriões transgênicos, e utilizando este marcador e a fosfatase alcalina determinou-se a origem e o padrão de migração destas células. O primeiro sinal de diferenciação das células germinativas primordiais é a expressão de fosfatase alcalina, e esta apareceu pela primeira vez na parte mais posterior da linha primitiva. No sétimo dia de desenvolvimento no embrião do camundongo, o endoderma visceral (AF+) é substituído pelo endoderma definitivo (AF-) originado na parte anterior da linha primitiva. O fator de transcrição Oct-4 é expresso nas CGP de ambos os sexos, pelo que acredita-se estar envolvido na mantença a totipotêncialidade das células. O receptor tirosina quinase, cujo ligante é o fator de Steel, é outra das moléculas que expressam as CGP. Tem sido demonstrado que este receptor possui um papel muito importante na sobrevivência deste tipo celular. Existem outros fatores que promovem a sobrevivência e/ou proliferação de CGP in vitro. Em experiências realizadas com o fator de transformação beta I (TGFβ-I), observou-se que este tem um efeito negativo sobre a proliferação das CGP. Outra atividade que tem sido postulada a este fator é o de um agente quimioatraente que possivelmente possa direcionar a migração destas células para a gônada. a) Um formado pelas células germinativas primordiais (precursoras dos gametas masculinos ou femininos), rodeadas de células somáticas das quais posteriormente se derivarão as células de Sertoli no macho e as células da granulosa na fêmea. b) O tecido que formará o estroma da gônada: tecido conjuntivo, vasos sanguíneos e as células intersticiais com atividade esteroidogênica (células de Leydig no testículo e a teca interna do ovário). As células somáticas do primórdio gonodal originam-se do mesoderma. Inicialmente são de três tipos: mesenquimáticas, mesoteliais e endoteliais. As células mesenquimáticas e mesoteliais iniciam grande atividade proliferativa ao chegar as CGP. Observa-se então uma condensação de células de origem mesotelial e mesenquimatoso que forma um agregado compacto denominado "blastema gonodal". A partir deste primórdio embrionário, diferenciam-se dois tecidos gonodais: os cordões sexuais e o estroma. Os cordões sexuais são arranjos epiteliais que se encontram delimitados por uma folha basal, e dentro deles encontramos as CGP. Por sua vez, no estroma encontram-se células do tipo mesenquimático e vasos sanguíneos. Neste momento, as gônadas são indiferenciadas e bipotencialmente sexuais, sendo impossível diferenciar, morfologicamente, uma gônada masculina de uma feminina, mas no caso dos machos genéticos já existe uma diferenciação da gônada a nível molecular. Nesta fase já se encontram presentes as estruturas das quais se desenvolvem os dutos mesonéfricos ou de Wolff precursores do aparelho genital masculino e os dutos paramesonéfricos ou de Müller que darão origem ao aparelho reprodutor feminino. Há uma série de fatores envolvidos no desenvolvimento precoce da gônada, entre os quais o fator esteroidogênico I (SFI: Steroidogenic fator l), que é um membro da subfamília de receptores nucleares, receptores órfãos. Este fator de transcrição tem um local de ligação ao DNA composto por dois dedos-de-Zinc. O SFI foi identificado como um ativador de genes envolvidos na biossíntese de esteroides em diferentes células. O SFI está presente durante o desenvolvimento embrionário em regiões associadas com funções endócrinas como gônadas, adrenais, pituitárias e hipotálamos. Os animais homozigotos para o gene SFI defeituoso, necessitam de gônadas e adrenais e têm a função gonadotrófica alterada. Os ratos sem SFI carecem de gonadotrofos e têm um desenvolvimento anormal do núcleo ventro-medial do hipotálamo; em particular as gônadas deixam de se desenvolver entre os dias 11 a 15 e degeneram-se por apoptose. No entanto, a crista genital forma-se e é colonizada pelas células germinativas, o que indica que estas continuam a receber o sinal adequado para a sua migração. Portanto, o SFI não está envolvido no desenvolvimento precoce da gônada e do sistema urogenital, mas parece estar envolvido na manutenção do crescimento das células somáticas presentes na gônada indiferenciada. O gene associado ao tumor de Wilms (WTI: Wilm's tumor Associated) está envolvido no desenvolvimento da gônada e do rim. Durante o desenvolvimento embrionário, WTI se expressa em todo o mesoderma intermediário e posteriormente na gônada indiferenciada, bem como no rim em formação. WTI regula o sinal indutivo do mesênquima para o epitélio celômico dos mesonefros. Se este for o caso, então WTI é responsável pelo crescimento da crista genital ao dirigir a entrada do epitélio celômico. Dado que estas células darão origem às células de Sertoli, a carência de WTI pode causar o desenvolvimento de embriões XY como fêmeas simplesmente porque não se formam as células de Sertoli. Em geral, todos os genes importantes na diferenciação do mesoderma intermediário e do sistema urogenital intervêm no desenvolvimento da gônada precoce. 1.4 DIFERENCIAÇÃO GONODAL O desenvolvimento das gônadas e ductos genitais descritos até o momento, é o mesmo para ambos os sexos. Igualmente, os genes descritos, que estão envolvidos no desenvolvimento das gônadas, ductos genitais e migração das células germinativas, afetam igualmente os embriões com genótipo XX ou XY. A gônada primitiva consiste anatomicamente de uma medula (interna) e uma crosta (externa), e de acordo com o local onde ocorre a colonização das células germinativas, diferenciara em testículo ou um ovário, respectivamente. Nos mamíferos, a primeira manifestação estrutural de diferenciação sexual é detectada na gônada dos machos, onde as células germinativas estão localizadas na medula. A diferenciação do testículo inicia-se quando os cordões sexuais se separam do epitélio celômico como consequência dos arranjos produzidos por uma invasão do mesênquima e vasos sanguíneos que provoca a compactação dos cordões, agora denominados cordões testiculares. As células que rodeiam os cordões se achatam e formam as células mioides, que são responsáveis pela formação das membranas basais. As células do epitélio interno, ou seja, as células de Sertoli, têm duas funções principais: o suporte das CGP e a síntese da hormona antimulleriana, responsável pela regressão dos ductos de Müller e secretada durante o período de diferenciação sexual. As células do estroma que rodeiam os cordões testiculares diferenciam-se para formar vários tipos de células: células mioides, fibroblastos, endotélio e células de Leydig, que são as mais importantes pela sua atividade endócrina. Posteriormente, os cordões testiculares dão origem aos túbulos seminíferos, que contêm o epitélio que produzirá os espermatozoides ao chegar à puberdade. Na fêmea, durante os estágios iniciais de diferenciação gonodal, não se observam mudanças em relação à gônada indiferenciada, só pode-se observar um certo crescimento devido à proliferação de células somáticas e germinativas. As células germinativas iniciam um período de proliferação, que termina com o início da meiose. Iniciada a meiose, dá-se o processo de foliculogênese; neste momento os cordões epiteliais se fragmentam, de tal maneira que cada ovócito fica rodeado de células epiteliais cobertas por uma folha basal fina (figura 1). Para que a gônada primitiva se desenvolva em testículo é indispensável a presença do cromossoma Y, independentemente do número de cromossomas X que contenha o genoma de um indivíduo. O gene determinante do testículo encontra-se localizado no cromossoma Y, denominado sry em ratos e SRY em humanos. O gene sry se expressa durante o desenvolvimento embrionário na crista genital de embriões de camundongos. A expressão é detectável no dia 10,5, pouco depois do aparecimento das cristas genitais, atinge o seu máximo durante o dia 11,5 e mantém-se até pouco depois de ocorrerem os primeiros sinais morfológicos de diferenciação testicular no dia 12,5. Este padrão de expressão é compatível com a teoria de que sry atua induzindo a ativação dos genes (figura 2) que conduzem ao desenvolvimento testicular, sem que exista a necessidade da expressão contínua de sry para manter a diferenciação do testículo após o dia 12,5. Como mencionado anteriormente, a gônada primitiva é composta por vários tipos de células. No entanto, as células germinativas primordiais não são o local de expressão do sry, já que os embriões que necessitam de células germinativas mantêm a expressão de sry e desenvolvem o sexo gonodal normalmente. As células somáticas na gônada em desenvolvimento incluem também as células de suporte. Sabe-se que é nestas células que o sry é expresso para que se diferenciem em células de Sertoli, e a expressão transitória de sry indica que deve ativar a outros genes para a manutenção das células de Sertoli. Uma vez diferenciadas as células de Sertoli, elas se encarregarão da diferenciação do resto das células na gônada. -/- Figura 1: Representação da diferenciação dos órgãos genitais internos. Adaptado de BRONSON, 1989. Figura 2: Cascada de genes envolvidos na diferenciação sexual, adaptado de KOOPMAN, 1999. O fator sry é necessário para a diferenciação do testículo. Embora não se conheçam os genes que provavelmente regulam esse gene, estudos realizados em camundongos demonstram que este gene parece coordenar-se com certos genes autossômicos. Entre estes genes autossômicos, o sox9, que é produzido pelas células de Sertoli uma vez que são estimuladas por sry, de modo que sox9 é um dos genes relacionados estruturalmente com sry. O Sox9 funciona como um fator de transcrição, mas não se sabe se a proteína tem qualquer outra função estrutural; este gene exprime-se abundantemente nos condrócitos e está relacionado com defeitos do aparelho ósseo chamados displasia campomélica. Curiosamente, os pacientes XY com esta condição sofrem frequentemente de reversão do sexo. O Sox9 é um dos poucos genes, além do SRY, do qual as mutações demonstraram interferir com a determinação sexual masculina. No entanto, apenas 75% dos pacientes com anomalias esqueléticas de tipo displasia campomélica têm reversão sexual e não foram encontrados casos de reversão sexual devido a um defeito de Sox9 que não seja acompanhado de defeitos esqueléticos. Isso indica que o Sox9 é apenas um membro da rede de genes que são ativados para determinar a diferenciação sexual, enquanto a rota que rege a condrogênese é mais sensível a perturbações deste. O momento em que se detecta a expressão do gene Sox9 (11dpc em ratos) coincide com a máxima expressão de sry, o que poderia indicar a possibilidade de que sry regule positivamente a Sox9. De fato, na região do promotor de Sox9 há um local de união ao que potencialmente se pode unir o sry. A expressão de Sox9 durante a diferenciação sexual sugere um papel abaixo de sry na diferenciação das células de Sertoli. O cromossoma X também é importante na diferenciação gonodal. O gene DAX-I foi isolado do lócus DSS (Dosage sensitive sex reversal) do cromossoma X. DAX-I é parte da cascata de determinação sexual, mas não é necessário para a formação do testículo. DAX-I é um membro dos receptores nucleares conhecidos como receptores órfãos. Este gene demonstrou ser um poderoso repressor da transcrição de SFI e de vários genes. Os padrões de expressão de DAX-I são complementares daqueles de SFI, ambos expressos nas cristas genitais. Em resumo, dada a evidência exposta, desenvolveu-se a hipótese de que DAX-I é um antagonista de sry; esse antagonismo é dependente dos níveis relativos de DAX-I e sry e de um limiar que varia de espécie para espécie. A DAX-I foi classificada como o gene antitestículo. Na fêmea (cariótipo XX) é importante que ocorra a inativação de um dos cromossomas sexuais X para que se mantenha o equilíbrio genético ao igualar o conteúdo de DNA dos cromossomas. Esse cromossoma inativado constitui o chamado corpúsculo de Barr. No entanto, para que a meiose se realize, é necessário dos dois cromossomas X ativos nos ovócitos para assegurar a diferenciação ovárica e a fertilidade. 1.5 DIFERENCIAÇÃO DOS DUCTOS SEXUAIS O embrião possui, além das gônadas indiferenciadas, dois sistemas de ductos: os de potencialidade masculina denominam-se ductos de Wolff ou mesonéfricos, e os de potencialidade feminina se chamam ductos de Müller ou paramesonéfricos (figura 1). Se a diferenciação gonodal levou à formação de um testículo, a partir do ducto mesonéfrico ou de Wolff se desenvolverão os ductos eferentes, o epidídimo, os ductos deferentes e as vesículas seminais. As hormonas importantes no desenvolvimento do aparelho genital masculino são a testosterona, produzida pelas células de Leydig, e sua forma 5α reduzida, a 5α di-hidrotestosterona. Acredita-se que a testosterona é responsável pela virilização dos ductos de Wolff, e a di-hidrotestosterona dos órgãos genitais externos. No macho, os canais de Müller atrofiam-se devido à ação de uma hormona fetal de origem testicular denominada hormona inibidora das estruturas de Müller (HIM) ou hormona antimulleriana. Este processo começa assim que os cordões espermáticos se formam e se diferenciam as células de Sertoli. A existência de HIM foi proposta baseada em estudos realizados em bezerras freemartin, devido à existência de uma hormona responsável pela atresia dos ductos de Müller que na fêmea dá origem ao útero e aos ovidutos. Essa hormona provoca a involução do aparelho genital do bovino nas gestações gemelares nas quais os produtos de diferente sexo têm comunicação sanguínea por ter ocorrido a anastomose dos vasos de ambas as placentas (figura 3). A HIM é uma glicoproteína pertencente à subfamília de TGFβ, é expressa pelas células que darão origem às células de Sertoli e é um dos primeiros marcadores de diferenciação nestas células. A HIM é secretada na vida adulta pelas células de Sertoli no testículo e por células da granulosa no ovário. No rato a HIM é expressa-se no 12° dia em um teste padrão que segue muito de perto o aumento na expressão de sry. No macho, esta secreção de HIM continua durante a vida fetal e adulta, contudo os níveis de HIM declinam na puberdade devido a um aumento na secreção de testosterona. Vários fatores intervêm na regulação do gene de HIM, incluindo os acima descritos SFI e Sox9. O gene HIM contém segmentos de DNA que são conservados em várias espécies de vertebrados. Existe um nexo de ligação para SFI, que ativa a transcrição de HIM. A mutação no local de ligação de SFI resulta em reversão do sexo em indivíduos XY incluindo genitais femininos normais, presença de um útero formado enfatizando a importância de SFI na determinação sexual e na expressão de HIM. Embora SFI seja um bom candidato como regulador de HIM, é expresso em outras células, como as de Leydig e adrenais, que não expressam HIM. Em contrapartida, Sox9 é expresso unicamente nas células de Sertoli que são as produtoras de HIM. O gene HIM também tem um nexo de ligação para Sox9. Além disso, Sox9 pode atuar sinergicamente com SFI para promover a secreção de HIM. Ao contrário destes dois fatores de transcrição, DAX-I antagoniza a ação de Sox9 e provavelmente SFI sobre o promotor de HIM. Assim, para que as células de Sertoli secretem HIM, a transcrição de DAX-I deve diminuir. Figura 3: Representação da diferenciação dos órgãos genitais externos. Adaptado de BRONSON, 1989. Os ductos de Wolff tornam-se o sistema de ejaculação do macho. A porção mais próxima dos testículos dá origem ao epidídimo, a parte central ao ducto deferente e a porção mais distal às vesículas seminais. A próstata e a parte membranosa da uretra do macho desenvolvem-se a partir da porção pélvica do seio urogenital. A virilização e diferenciação dos ductos de Wolff dependem da produção de testosterona pelo testículo. Quanto aos órgãos genitais externos do macho, o tubérculo genital é ampliado e as dobras uretrais se fundem para formar a uretra peniana. A fusão das dobras uretrais aproxima os tubérculos genitais para formar o escroto (figura 4). Figura 4: Diferenciação do aparelho genital da fêmea e do macho. Adaptado de KOOPMAN, 1989. A diferenciação dos órgãos genitais da fêmea ocorre de forma passiva, já que a ausência de testículos e por isso da hormona inibidora dos ductos de Müller (HIM), assim como dos andrógenos virilizantes, favorece o desenvolvimento dos ductos de Müller, enquanto os de Wolff sofrem atrofia. A porção cefálica dos ductos de Müller dá origem aos ovidutos, que na sua terminação caudal se fundem com o útero. O contato dos ductos de Müller com o seio urogenital induz uma intensa proliferação celular que resulta na formação da área uterovaginal localizado entre o seio urogenital e os ductos de Müller. As células do prato uterovaginal proliferam e aumentam a distância entre as duas estruturas criando o espaço que formará a vagina quando o prato é canalizado e forma um lúmen. Em contraste com o que ocorre no macho, na fêmea a maior parte do seio urogenital se mantém exposta na superfície da abertura onde desembocam a vagina e a uretra. O tubérculo urogenital da fêmea tem um crescimento limitado e forma o clitóris. A sequência de passos da diferenciação sexual do aparelho genital é resumida na tabela 1. Tabela 1: Destino em desenvolvimento dos rudimentos sexuais dos fetos macho e fêmea dos mamíferos -/- Rudimento sexual Macho Fêmea Gônada Testículo Ovário Ductos de Müller (Paramesonéfricos) Vestígios Útero, parte da vagina, ovidutos Ductos de Wolff (Mesonéfricos) Ductos eferentes deferentes, epidídimo, vesículas seminais Vestígios Seio urogenital Uretra, próstata, glândulas bulbouretrais Parte da vagina, uretra, vestíbulo, glândulas vestibulares Tubérculo genital Pênis Clitóris Pregas vestibulares Escroto Lábios vulvares Fonte: HAFEZ, 2004. 1.6 DIFERENCIAÇÃO SEXUAL DO HIPOTÁLAMO Os processos de diferenciação sexual não se limitam apenas às células somáticas do organismo do feto, mas incluem também os centros nervosos superiores do cérebro. Assim, da mesma maneira que a gônada e os ductos sexuais se desenvolvem para o tipo feminino ou masculino, propôs-se que o cérebro pode ser "masculinizado" ou permanecer "Feminizado". A diferenciação do hipotálamo vai depender do ambiente esteroidal do neonato e ocorre na fase perinatal. Estes eventos serão de grande transcendência na vida reprodutiva do indivíduo. Tanto a fêmea como o macho nascem com a capacidade de secreção de gonadotropinas de acordo com um padrão cíclico; contudo, no macho, a exposição do hipotálamo à ação dos andrógenos testiculares durante os primeiros dias da vida extrauterina provoca a masculinização, com o qual o hipotálamo do macho é programado para que a secreção de gonadotropinas se realize a um ritmo relativamente constante por parte da hipófise (secreção tônica). Na fêmea, tanto a secreção tônica como a cíclica se conservam. No entanto, observou-se que a injeção de testosterona ou o transplante de testículo na rata fêmea durante os primeiros dias de vida, suprime a sua futura atividade estral (secreção cíclica). Por outro lado, se os ovários forem transplantados para o rato macho normal castrado na idade adulta, o animal não desenvolve qualquer atividade cíclica, mas se os machos transplantados forem castrados ao nascer, o ovário é capaz de efetuar mudanças cíclicas e ovulações. Isto foi demonstrado em roedores, mas não em animais domésticos ou na espécie humana. Portanto, o padrão de secreção de gonadotropinas, seja cíclico ou tônico, não depende da hipófise, mas do hipotálamo e sua correta diferenciação. 1.7 CONCLUSÕES A maioria dos conhecimentos no campo da biologia do desenvolvimento e, muito especificamente, dos processos de diferenciação sexual têm sido originados de estudos relacionados com desordens congênitas, que na sua maioria devem-se a defeitos de genes específicos. A análise detalhada destas desordens permitiu entender alguns mecanismos endócrinos, moleculares e genéticos envolvidos na diferenciação sexual. A identificação do gene sry como determinante do testículo foi uma contribuição crucial e abriu as portas à compreensão dos mecanismos moleculares e celulares relacionados com o desenvolvimento do testículo. Se este gene não estiver presente, é criado um programa genético alternativo para levar a cabo a diferenciação gonodal para o ovário. Finalmente, devemos ter presente que é necessária uma correlação entre mudanças morfológicas e expressão de genes durante o desenvolvimento para entender os mecanismos relacionados com a diferenciação. -/- Apoio -/- Realização -/- REFERÊNCIAS BIBLIOGRÁFICAS ANDERSON, Robert et al. The onset of germ cell migration in the mouse embryo. Mechanisms of development, v. 91, n. 1-2, p. 61-68, 2000. AUSTIN, Colin Russell; SHORT, R. V. Reproduction in Mammals: Volume 1, Germ Cells and Fertilization. Londres: Cambridge University Press, 1972. BRONSON, Franklin H. Mammalian reproductive biology. Chicago: University of Chicago Press, 1989. BUEHR, Mia. The primordial germ cells of mammals: some current perspectives. Experimental cell research, v. 232, n. 2, p. 194-207, 1997. BYSKOV, Anne G. Differentiation of mammalian embryonic gonad. Physiological reviews, v. 66, n. 1, p. 71-117, 1986. CAPEL, Blanche et al. Migration of mesonephric cells into the mammalian gonad depends on Sry. Mechanisms of development, v. 84, n. 1-2, p. 127-131, 1999. CAPEL, Blanche. The battle of the sexes. Mechanisms of development, v. 92, n. 1, p. 89-103, 2000. DERIVAUX, Jules; BARNABÉ, Renato Campanarut. Reprodução dos animais domésticos. Zaragoza: Acribia, 1980. DOMENICE, Sorahia et al. Aspectos moleculares da determinação e diferenciação sexual. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 46, n. 4, p. 433-443, 2002. DONAHOE, Patricia K. et al. Mullerian inhibiting substance activity in bovine fetal, newborn and prepubertal testes. Biology of reproduction, v. 16, n. 2, p. 238-243, 1977. HAFEZ, Elsayed Saad Eldin; HAFEZ, B. Reprodução animal. São Paulo: Manole, 2004. HANLEY, Neil A. et al. Steroidogenic factor 1 (SF-1) is essential for ovarian development and function. Molecular and cellular endocrinology, v. 163, n. 1-2, p. 27-32, 2000. HIORT, Olaf; PAUL-MARTIN, H. The molecular basis of male sexual differentiation. European journal of endocrinology, v. 142, n. 2, p. 101-110, 2000. HOLY, Lubos; MARTÍNEZ JÚSTIZ, G. Colab. Biología de la reproducción bovina. Havana: Revolucionária, 1975. JOSSO, Nathalie et al. The role of anti-Müllerian hormone in gonadal development. Molecular and cellular endocrinology, v. 145, n. 1-2, p. 3-7, 1998. JOST, Alfred et al. Studies on sex differentiation in mammals. In: Proceedings of the 1972 Laurentian Hormone Conference. Londres: Academic Press, 1973. p. 1-41. KNOBIL, Ernst. Knobil and Neill's physiology of reproduction. EUA: Gulf Professional Publishing, 2006. KOFMAN ALFARO, S.; MERCHANT LARIOS, H.; PEREZ PALACIOS, G. Diferenciacion sexual. I. Bases biologicas del dimorfismo sexual. Rev. invest. clín, p. 349-59, 1982. KOOPMAN, Peter. Sry and Sox9: mammalian testis-determining genes. Cellular and Molecular Life Sciences CMLS, v. 55, n. 6-7, p. 839-856, 1999. MCDONALD, L. E. Veterinary endocrinology. Lea & Febiger, Philadelphia, Pa, 1969. MEIZEL, S.; JOHNSON, M. H. Development in mammals. MH Johnson, Ed, v. 3, p. 1-64, 1978. MELLO, Maricilda Palandi de; ASSUMPÇÃO, Juliana de G.; HACKEL, Christine. Genes envolvidos na determinação e diferenciação do sexo. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 49, n. 1, p. 14-25, 2005. -/- REFERÊNCIAS BIBLIOGRÁFICAS MERCHANT-LARIOS, H. Ovarian differentiation. The Vertebrate Ovary, p. 47-81, 1978. MIES FILHO, Antonio. Reprodução dos animais. Porto Alegre: Sulina, 1987. NEF, Serge; PARADA, Luis F. Hormones in male sexual development. Genes & Development, v. 14, n. 24, p. 3075-3086, 2000. PARKER, Keith L.; SCHEDL, Andreas; SCHIMMER, Bernard P. Gene interactions in gonadal development. Annual review of physiology, v. 61, n. 1, p. 417-433, 1999. SWAIN, Amanda; LOVELL-BADGE, Robin. Mammalian sex determination: a molecular drama. Genes & development, v. 13, n. 7, p. 755-767, 1999. WILHELM, Dagmar; PALMER, Stephen; KOOPMAN, Peter. Sex determination and gonadal development in mammals. Physiological reviews, v. 87, n. 1, p. 1-28, 2007. WILSON, Jean D.; GRIFFIN, James E.; GEORGE, Fredrick W. Sexual differentiation: early hormone synthesis and action. Biology of reproduction, v. 22, n. 1, p. 9-17, 1980. -/- Emanuel Isaque Cordeiro da Silva Belo Jardim, 07 de Maio de 2020. (shrink)

Gender classifications often are controversial. These controversies typically focus on whether gender classifications align with facts about gender kind membership: Could someone really be nonbinary? Is Chris Mosier really a man? I think this is a bad approach. Consider the possibility of ontological oppression, which arises when social kinds operating in a context unjustly constrain the behaviors, concepts, or affect of certain groups. Gender kinds operating in dominant contexts, I argue, oppress trans and nonbinary persons in this way: they marginalize (...) trans men and women, and exclude nonbinary persons. As a result, facts about membership in dominant gender kinds should not settle gender classification practices. (shrink)

Considérez les énoncés suivants : « La bombe a causé la destruction du pont » ; « L’explosion de la bombe a causé la destruction du pont » ; « Booth a causé la mort de Lincoln » ; et « Le tir de Booth a causé la mort de Lincoln ». Ces énoncés suggèrent que les objets, tels que les bombes ou les personnes, font partie de la catégorie ontologique des causes, au même titre que les évènements, comme le (...) tir de Booth et l’explosion de la bombe. À première vue, le fait que les objets et les personnes puissent être des causes n’a rien de particulièrement surprenant. Cependant, les philosophes du XXe siècle ont fait preuve d’une extrême méfiance à l’égard de cette idée. Une majorité de philosophes ont trouvé l’idée même de causalité par des objets ou des agents inintelligible, à tel point que les théories standards de la causalité présupposent que les entités reliées comme causes à effets sont des évènements, ou encore des faits, des propriétés ou des états. Pourtant, cette hostilité à l’égard de la causalité des objets est relativement récente ; la causalité agentive semble, au moins jusqu’à Thomas Reid (1710-1796), avoir été la norme, et non le mystère. La mise à l’écart des objets et des agents de la catégorie de cause est-elle justifiée ? Un nombre grandissant de philosophes, les agentialistes (agent-causalists), soutiennent que non et cherchent à réhabiliter l’idée de causalité agentive (par des agents) et/ou substantielle (par des substances), tandis que d’autres, les évènementialistes (event-causalists), défendent que celle-ci est au mieux réductible à la causalité entre évènements, ou au pire que l’idée est incohérente. L’importance de cette question n’est pas négligeable, car elle revient à demander quels sont les moteurs du changement. En effet, nous voulons savoir si certains objets tels que les couteaux, les bombes, les animaux et les personnes sont parfois à l’origine du changement, ou si tout effet procède uniquement de changements antérieurs, d’évènements. Existe-t-il une relation causale, la causalité agentive ou substantielle, reliant objets et changements, différente des relations causales habituellement traitées par les philosophes de la causalité ? Quelle est sa relation avec la causalité évènementielle ? Et comment fonctionne-t-elle ? (shrink)

Many of us hold false beliefs about matters that are relevant to public policy such as climate change and the safety of vaccines. What can be done to rectify this situation? This question can be read in two ways. According to the descriptive reading, it concerns which methods will be effective in persuading people that their beliefs are false. According to the normative reading, it concerns which methods we are permitted to use in the service of persuading people. Some effective (...) methods—a programme of brainwashing, say—would not be permissible. In this paper I compare “methods of rational persuasion” with what you might call “marketing methods” such as how one frames the problem of climate change. My aim is to show that “marketing methods” are preferable to “methods of rational persuasion”. My argument has two parts. First, I argue that the evidence suggests that “marketing methods” are more effective in persuading people to change their minds. Second, I argue that “marketing methods” are an acceptable response to the normative question. (shrink)

We want to know what gender is. But metaphysical approaches to this question solely have focused on the binary gender kinds men and women. By overlooking those who identify outside of the binary–the group I call ‘genderqueer’–we are left without tools for understanding these new and quickly growing gender identifications. This metaphysical gap in turn creates a conceptual lacuna that contributes to systematic misunderstanding of genderqueer persons. In this paper, I argue that to better understand genderqueer identities, we must recognize (...) a new type of gender kind: critical gender kinds, or kinds whose members collectively destabilize one or more pieces of dominant gender ideology. After developing a model of critical gender kinds, I suggest that genderqueer is best modeled as a critical gender kind that destabilizes the ‘binary axis’, or the piece of dominant gender ideology that says that the only possible genders are the binary, discrete, exclusive, and exhaustive kinds men and women. (shrink)

Alex Byrne’s article, “Are Women Adult Human Females?”, asks a question that Byrne treats as nearly rhetorical. Byrne’s answer is, ‘clearly, yes’. Moreover, Byrne claims, 'woman' is a biological category that does not admit of any interpretation as (also) a social category. It is important to respond to Byrne’s argument, but mostly because it is paradigmatic of a wider phenomenon. The slogan “women are adult human females” is a political slogan championed by anti-trans activists, appearing on billboards, pamphlets, and anti-trans (...) online forums. In this paper, I respond to Byrne’s argument, revealing significant problems with its background assumptions, content, and methodology. (shrink)

In this article, Dembroff argues that the category nonbinary should not be understood in terms of presentation or psychological states, but instead in terms of how its members are politically situated with respect to the binary expectations of Western gender ideology.

When one takes an intersectional perspective on patterns of oppression and domination, it becomes clear that familiar forms of systemic injustice, such as misogyny and anti-Black racism, are inseparable. Some feminist theorists conclude, from this, that the systems behind these injustices cannot be individuated—for example, that there isn’t patriarchy and white supremacy, but instead only white supremacist patriarchy. This chapter offers a different perspective. Philosophers have long observed that a statue and a lump of clay can be individuated although inseparable, (...) and that statues and lumps of clay do different explanatory and predictive work for the same causal outcomes. This chapter suggests that the same is true of systems such as patriarchy and white supremacy. These systems, like the injustices they produce, are inseparable. But they can be individuated, and when they are individuated, they do different explanatory and predictive work. (shrink)

There has been extensive discussion of testimonial epistemic injustice, the phenomenon whereby a speaker’s testimony is rejected due to prejudice regarding who they are. But people also have their testimony rejected or preempted due to prejudice regarding what they communicate. Here, the injustice is content focused. We describe several cases of content focused injustice, and we theoretically interrogate those cases by building up a general framework through which to understand them as a genuine form of epistemic injustice that stands in (...) intertwined relationships to other forms of epistemic injustice. (shrink)

The slogan “Do Your Own Research” (DYOR) is often invoked by people who are distrustful, even downright sceptical, of recognized expert authorities. While this slogan may serve various rhetorical purposes, it also expresses an ethic of inquiry that valorises independent thinking and rejects uncritical deference to recognized experts. This paper is a qualified defence of this ethic of inquiry in one of the central contexts in which it might seem attractive. I use several case studies of patient activist groups to (...) argue that these groups often engage in valuable independent research that advances biomedical knowledge. In doing so they demonstrate the value of “lay expertise” and the epistemic as well as political necessity of not simply deferring to recognized experts. I also give some reasons why patient activist groups often produce valuable biomedical knowledge: they are examples of what I call “research collectives”. Research collectives are research communities that differ from the traditional research communities we find in universities and research institutes in that their members typically lack formal relevant scientific credentials and training. But they are similar in that they have internal structures—training procedures, norms of discussion, venues for holding discussions—that facilitate the production of knowledge. I finish by suggesting that future research into the differences and similarities between research collectives and traditional research communities is required. (shrink)

In this paper, we defend two main claims. The first is a moderate claim: we have a negative duty to not use binary gender-specific pronouns he or she to refer to genderqueer individuals. We defend this with an argument by analogy. It was gravely wrong for Mark Latham to refer to Catherine McGregor, a transgender woman, using the pronoun he; we argue that such cases of misgendering are morally analogous to referring to Angel Haze, who identifies as genderqueer, as he (...) or she. The second is a radical claim: we have a negative duty to not use any gender-specific pronouns to refer to anyone, regardless of their gender identity. We offer three arguments in favor of this claim (which appeal to concerns about inegalitarianism and risk, invasions of privacy, and reinforcing essentialist ideologies). We also show why the radical claim is compatible with the moderate claim. Before concluding, we examine common concerns about incorporating either they or a neologism such as ze as a third-person singular gender-neutral pronoun. These concerns, we argue, do not provide sufficient reason to reject either the moderate or radical claim. (shrink)

What’s important about ‘coming out’? Why do we wear business suits or Star Trek pins? Part of the answer, we think, has to do with what we call agential identity. Social metaphysics has given us tools for understanding what it is to be socially positioned as a member of a particular group and what it means to self-identify with a group. But there is little exploration of the general relationship between self-identity and social position. We take up this exploration, developing (...) an account of agential identity—the self-identities we make available to others. Agential identities are the bridge between what we take ourselves to be and what others take us to be. Understanding agential identity not only fills an important gap in the literature, but also helps us explain politically important phenomena concerning discrimination, malicious identities, passing, and code-switching. These phenomena, we argue, cannot be understood solely in terms of self-identity or social position. (shrink)

In a recent article in this journal, Mona Simion argues that Sally Haslanger’s “engineering” approach to gender concepts such as ‘woman’ faces an epistemic objection. The primary function of all concepts—gender concepts included—is to represent the world, but Haslanger’s engineering account of ‘woman’ fails to adequately represent the world because, by her own admission, it doesn’t include all women in the extension of the concept ‘woman.’ I argue that this objection fails because the primary function of gender concepts—and social kind (...) concepts in general—is not (merely) to represent the world, but rather to shape it. I finish by considering the consequences for “conceptual engineering” in philosophy more generally. While Haslanger’s account may escape Simion’s objection, other appeals to conceptual engineering might not fair so well. (shrink)

We live in a world saturated in both racial and gendered divisions. Our focus is on one place where attitudes about these divisions diverge: language. We suspect most everyone would be horrified at the idea of adding race-specific pronouns, honorifics, generic terms, and so on to English. And yet gender-specific terms of the same sort are widely accepted and endorsed. We think this asymmetry cannot withstand scrutiny. We provide three considerations against incorporating additional race-specific terms into English, and argue that (...) these considerations also support eliminating the analogous gender-specific terms. With respect to these parts of speech, English should be no more gender-specific than it already is race-specific. (shrink)

Ordinary discourse is filled with discussions about ‘sexual orientation’. This discourse might suggest a common understanding of what sexual orientation is. But even a cursory search turns up vastly differing, conflicting, and sometimes ethically troubling characterizations of sexual orientation. The conceptual jumble surrounding sexual orientation suggests that the topic is overripe for philosophical exploration. This paper lays the groundwork for such an exploration. In it, I offer an account of sexual orientation – called ‘Bidimensional Dispositionalism’ – according to which sexual (...) orientation concerns what sex[es] and gender[s] of persons one is disposed to sexually engage, and makes no reference to one’s own sex and gender. (shrink)

One of the moral questions concerning autonomous vehicles (henceforth AVs) is the choice between types that differ in their built-in algorithms for dealing with rare situations of unavoidable lethal collision. It does not appear to be possible to avoid questions about how these algorithms should be designed. We present the results of our study of moral preferences (N = 2769) with respect to three types of AVs: (1) selfish, which protects the lives of passenger(s) over any number of bystanders; (2) (...) altruistic, which minimizes the number of casualties, even if this leads to death of passenger(s); and (3) conservative, which abstains from interfering in such situations. We differentiate between scenarios in which participants are to make their decisions privately or publicly, and for themselves or for their offspring. We aim to answer two research questions: (1) whether the public visibility of the choice of an AV type choice make this choice more altruistic and (2) which type of situation makes it more difficult to choose altruistically: when choosing for society as a whole, when choosing only for oneself, or when choosing only for one’s offspring. Our results show that respondents exhibit a preference for an altruistic strategy for AVs and that it is reinforced when signaled to others. The altruistic preference is strongest when applies to everybody else, weaker when it reflects a solely personal choice, and weakest when choosing for one’s own child. We conclude that a public choice is considerably more likely to pressure consumers into accepting a more socially beneficial solution. (shrink)

Spanish Translation of "He/She/They/Ze" (Ergo, 2018).

Most discussions of racial fetish center on the question of whether it is caused by negative racial stereotypes. In this paper I adopt a different strategy, one that begins with the experiences of those targeted by racial fetish rather than those who possess it; that is, I shift focus away from the origins of racial fetishes to their effects as a social phenomenon in a racially stratified world. I examine the case of preferences for Asian women, also known as ‘yellow (...) fever’, to argue against the claim that racial fetishes are unobjectionable if they are merely based on personal or aesthetic preference rather than racial stereotypes. I contend that even if this were so, yellow fever would still be morally objectionable because of the disproportionate psychological burdens it places on Asian and Asian-American women, along with the role it plays in a pernicious system of racial social meanings. (shrink)

Analytic philosophy has transgender trouble. In this paper, I explore potential explanations for this trouble, focusing on the notion of 'cisgender commonsense' and its place in philosophical methodology.

In this peer commentary on Maura Priest's "Transgender Children and the Right to Transition: Medical Ethics When Parents Mean Well but Cause Harm", I argue against the "mismatch" model of trans identity. On this model, which is prevalent in institutional and medical contexts, to be trans is to have one's gender identity "mismatch" with one's sexed body.

The view that to act is to cause change and that to be an agent is to be the causer of an action’s result has gained traction in the past twenty years or so. This view seems to have two significant corollaries. First, there is no distinction between doing an action and causing its result. Second, any two actions that have the same result will turn out to be identical. Ruben (2018) has recently used the first corollary to challenge the (...) view, and the second corollary raises further problems for the view. This article aims to refine this view and defend it against the challenges that arise out of its two corollaries. It is argued that being the cause of an action’s result is not the same as being its causer and that doing an action is not just causing its result but causing it in a specific way. (shrink)

In her provocative discussion of the challenge posed to the traditional impartialist, justice-focused conception of morality by the new-wave care perspective in ethics, Annette Baier calls for ‘a “marriage” of the old male and newly articulated female... moral wisdom,’ to produce a new ‘cooperative’ moral theory that ‘harmonize[s] justice and care.’ I want in this paper to play matchmaker, proposing one possible conjugal bonding: a union of two apparently dissimilar modes of what Nel Noddings calls ‘meeting the other morally,’ a (...) wedding of respect and care. (shrink)

Recent work in psychology on ‘cultural cognition’ suggests that our cultural background drives our attitudes towards a range of politically contentious issues in science such as global warming. This work is part of a more general attempt to investigate the ways in which our wants, wishes and desires impact on our assessments of information, events and theories. Put crudely, the idea is that we conform our assessments of the evidence for and against scientific theories with clear political relevance to our (...) pre-existing political beliefs and convictions. In this paper I explore the epistemological consequences of cultural cognition. What does it mean for the rationality of our beliefs about issues such as global warming? I argue for an unsettling conclusion. Not only are those on the ‘political right’ who reject the scientific consensus on issues like global warming unjustified in doing so, some of those on the ‘political left’ who accept the consensus are also unjustified in doing so. I finish by addressing the practical implications of my conclusions. (shrink)

It is commonly observed that we live in an increasingly polarised world. Strikingly, we are polarised not only about political issues, but also about scientific issues that have political implications, such as climate change. This raises two questions. First, why are we so polarised over these issues? Second, does this mean our views about these issues are all equally ir/rational? In this chapter I explore both questions. Specifically, I draw on the literature on ideologically motivated reasoning to develop an answer (...) to the first question. Put briefly, we exhibit “directional biases” in our information processing: we try to assimilate new information into our existing webs of beliefs. This means that those who are predisposed to accept the case for climate change end up accepting it, whereas those who are predisposed to reject it end up rejecting it. Based on this answer, I then address the second question. I look at some reasons for thinking that, because we all exhibit such biases in our thinking, we are all equally rational (or, as the case may be, irrational). I also suggest some ways you might try reject these reasons. (shrink)

Skeptical invariantism isn’t a popular view about the semantics of knowledge attributions. But what, exactly, is wrong with it? The basic problem is that it seems to run foul of the fact that we know quite a lot of things. I agree that it is a key desideratum for an account of knowledge that it accommodate the fact that we know a lot of things. But what sorts of things should a plausible theory of knowledge say that we know? In (...) this paper I sketch an answer to this question and then apply it to skeptical invariantism. I start by distinguishing between a “radical” skeptical invariantist position (on which the standards for knowing are so high that we rarely if ever satisfy them) and a more “moderate” skeptical invariantist position (on which the standards are very hard, but not impossible, to satisfy). I then argue that, while radical forms of skeptical invariantism are clearly not going to do a good job of satisfying the key desideratum, more moderate forms can do quite well with respect to it. In particular, I argue the version of moderate skeptical invariantism defended by Davide Fassio can plausibly satisfy it. (shrink)

Giving money to others feels good. It is now standard to use the label ‘warm glow feelings’ to refer to the pleasure people take from giving. But what exactly are warm glow feelings? And why do people experience them? To answer these questions, we ran two studies: a recall task in which participants were asked to remember a donation they made, and a donation task in which participants were given the opportunity to make a donation before reporting their affective states. (...) Correlational and experimental results converge towards the conclusion that, if the nature of the warm glow is straightforward, its source is multifaceted. Regarding the nature of the ‘warm glow’, the pleasure people took in giving was mainly predicted by one particular type of positive emotion and was indeed described by participants as ‘warm’. Regarding the underlying psychological mechanisms, warm glow feelings were elicited by positive appraisals regarding the donor’s moral character, positive appraisals regarding the actual impact of the donor’s donation on the welfare of others and a feeling of communion with others. We discuss the theoretical implications of our findings. (shrink)

Epistemic contextualists think that the truth-conditions of ‘knowledge’ ascriptions depend in part on the context in which they are uttered. But what features of context play a role in determining truth-conditions? The idea that the making salient of error possibilities is a central part of the story has often been attributed to contextualists, and a number of contextualists seem to endorse it (see Cohen (Philos Perspect, 13:57–89, 1999) and Hawthorne, (Knowledge and lotteries, Oxford University Press, Oxford, 2004)). In this paper (...) I argue that the focus on salience relations is a mistake. On the view I defend, the relevant features of context are facts about what error-possibilities and alternatives those in the context have a reason to consider, not facts about what error-possibilities and alternatives those in the context actually consider. As I will argue, this view has certain advantages over the standard view. (shrink)

Dog whistling—speech that seems ordinary but sends a hidden, often derogatory message to a subset of the audience—is troubling not just for our political ideals, but also for our theories of communication. On the one hand, it seems possible to dog whistle unintentionally, merely by uttering certain expressions. On the other hand, the intention is typically assumed or even inferred from the act, and perhaps for good reason, for dog whistles seem misleading by design, not just by chance. In this (...) paper, I argue that, to understand when and why it’s possible to dog-whistle unintentionally (and indeed, intentionally), we’ll need to recognize the structure of our linguistic practices. For dog whistles and for covertly coded speech more generally, this structure is a pair of practices, one shared by all competent speakers and the other known only to some, but deployable in the same contexts. In trying to identify these enabling conditions, we’ll discover what existing theories of communicated content overlook by focusing on particular utterances in isolation, or on individual speakers’ mental states. The remedy, I argue, lies in attending to the ways in which what is said is shaped by the temporally extended, socio-politically structured linguistic practices that utterances instantiate. (shrink)

Pragmatic encroachers argue that whether you know that p depends on a combination of pragmatic and epistemic factors. Most defenses of pragmatic encroachment focus on a particular pragmatic factor: how much is at stake for an individual. This raises a question: are there reasons for thinking that knowledge depends on other pragmatic factors that parallel the reasons for thinking that knowledge depends on the stakes? In this paper I argue that there are parallel reasons for thinking that knowledge depends on (...) social factors such as one’s social role or identity. I call this social encroachment. After defending social encroachment, I compare and contrast social encroachment with some key ideas in feminist epistemology. I argue that, while there are some important similarities, there are also some important differences. I finish by commenting on what I take the upshots of these differences to be. (shrink)

In the consolidated cases Altitude Express v. Zarda, Bostock v. Clayton County, and R.G. & G.R. Harris Funeral Homes v. EEOC, the Supreme Court will decide whether or not Title VII prohibits discrimination on the basis of sexual orientation or gender identity. Although the parties disagree as to the appropriate formulation of a but-for test to determine whether or not there was a discriminatory outcome, all parties do agree to the use of such a test, which asks “whether the evidence (...) shows ‘treatment of a person in a manner which but for that person’s sex would be different.’” City of Los Angeles, Dep’t. of Water and Power v. Manhart, 435 U.S. 702, 711 (1978). However, but-for tests confuse more than they clarify the inquiry; a discriminatory outcome cannot be explained by appeal to just a discrete characteristic of a particular person. Individuals are not discriminated against because of these characteristics per se. Rather, they are discriminated against because of the social meanings and expectations that attach to these characteristics. Beyoncé and Taylor Swift illustrate the difference between individual-level causation and social explanation in two separate songs, “If I Were a Boy” and “The Man.” The explanation for why the counterfactual ‘male’ Beyoncé and Swift are evaluated differently than their current ‘female’ versions does not lie in individual-level features considered apart from the social world, but in social-level roles and expectations associated with those features. For this reason, a social explanation test—one that asks whether the social meanings of sex characteristics, rather than the characteristics per se, explain the outcome in question—is more suitable for determining whether or not Title VII has been violated. (shrink)

'Transgender’ is often described either as an identity, or else as the full spectrum of gender nonconformity. In this essay, I suggest that these descriptions do not align with the conceptual labor that we often ask ‘transgender’ to do: highlighting people who engage in forms of self-directed gender nonconformity that are heavily penalized.

Twice in the 2020 term, in Bostock and Comcast, the Supreme Court doubled down on the reasoning of “but-for causation” to interpret antidiscrimination statutes. According to this reasoning, an outcome is discriminatory because of some status—say, sex or race—just in case the outcome would not have occurred “but-for” the plaintiff’s status. We think this reasoning embeds profound conceptual errors that render the decisions deeply confused. Furthermore, those conceptual errors tend to limit the reach of antidiscrimination law. In this essay, we (...) first unpack the ambiguity of this but-for causal reasoning. We then show that this reasoning arises from a misapplication of tort law principles within antidiscrimination law, and that, as a result, it is both conceptually and normatively indeterminate. (shrink)

The idea that the concept ‘knowledge’ has a distinctive function or social role is increasingly influential within contemporary epistemology. Perhaps the best-known account of the function of ‘knowledge’ is that developed in Edward Craig’s Knowledge and the state of nature (1990, OUP), on which (roughly) ‘knowledge’ has the function of identifying good informants. Craig’s account of the function of ‘knowledge’ has been appealed to in support of a variety of views, and in this paper I’m concerned with the claim that (...) it supports a sort of epistemic contextualism, which is (roughly) the view that the semantic contents and truth-conditions of ‘knowledge’ ascriptions - instances of ‘S knows that p’- depend on and vary with the context of ascription (see, for instance, John Greco’s ‘What’s wrong with contextualism’, Philosophical Quarterly [2008]). Prima facie, this claim should strike us as surprising. A number of concepts and linguistic items (words, sentences) serve functions that have little or nothing to do with semantics. However, I argue that, on the best interpretation of talk of the function of a concept such as ‘knowledge’, the function of ‘knowledge’ is relevant to semantics. Along the way I also suggest how to improve on what I call the ‘usual argument’ that Craig’s account of the function of ‘knowledge’ supports epistemic contextualism. (shrink)

“Political epistemology” has recently emerged as an area of analytic epistemology. While it may not be an entirely new area, and its precise boundaries are up for negotiation, recent political events in the UK (e.g. Brexit) and the US (e.g. the election of Donald Trump) played a key role in its rise to prominence within contemporary analytic epistemology. Further, political epistemology is an inter-disciplinary field, drawing on relevant work in political science, political psychology, and science communication that is often equally (...) focused on the UK and US. Political epistemology is therefore parochial, though it is the kind of parochialism that is not always conscious of itself as parochial. In this talk I adopt a critical stance towards parochialism in political epistemology. But my aim is not just to point out the mistakes that can result from a parochial concern with political events in one’s own country. I suggest that we can view political epistemology as interested in certain fundamental problems and tensions, which political epistemologists may then seek to identify and address within the political context in which they are working. (shrink)

Interviewet er lavet i juli 2021. Dets formål er at belyse emner, der er centrale i Celikates’ tænkning, f.eks. den voksende højrefløjspopulisme, migration, voldelige versus ikke-voldelige protester, civil ulydighed og den kritiske filosofis rolle i dag. -/- When Celikates and I sat down digitally in July 2021, the interview’s primary purpose was to examine topics central to Celikates’ thinking, such as the rise of right-wing populism, migration, violent versus non-violent protest, civil disobedience, and the role of critical philosophy today.

Many have rejected contextualism about ?knows? because the view runs into trouble with intra- and inter-contextual disagreement reports. My aim in this paper is to show that this is a mistake. First, I outline four desiderata for a contextualist solution to the problem. Second, I argue that two extant solutions to the problem fail to satisfy the desiderata. Third, I develop an alternative solution which satisfies the four desiderata. The basic idea, put roughly, is that ?knowledge? ascriptions serve the function (...) of recommending good informants, and disagreement over ?knowledge? ascriptions is a matter of conflicting recommendations. The upshot is that intra- and inter-contextual disagreement reports provide little?if any?reason to reject contextualism. (shrink)

A number of examples have been given of physical systems (both classical and quantum mechanical) which when provided with a (continuously variable) computable input will give a non-computable output. It has been suggested that these systems might allow one to design analogue machines which would calculate the values of some number-theoretic non-computable function. Analysis of the examples show that the suggestion is wrong. In Section 4 I claim that given a reasonable definition of analogue machine it will always be wrong. (...) The claim is to be read not so much as a dogmatic assertion, but rather as a challenge. -/- In Sections 1 and 2 I discuss analogue machines, and lay down some conditions which I believe they must satisfy. In Section I discuss the particular forms which a paradigm undecidable problem (or non-computable function) may take. In Sections 5 and 6 I justify any claim for two particular examples lying within the range of classical physics, and in Section 7 I justify it for two (closely connected) examples from quantum mechanics, and discuss, very briefly, other possible quantum mechanical situations. Section 8 contains various remarks and comments. In Section 9 I consider the suggestion made by Penrose that a (future) theory of quantum gravity may predict non-locally-determined, and perhaps non-computable patterns of growth for microsopic structures. My conclusion is that such a theory will have to have non-computability built into it. (shrink)

In this paper I consider the prospects for pluralism about knowledge, that is, the view that there is a plurality of knowledge relations. After a brief overview of some views that entail a sort of pluralism about knowledge, I focus on a particular kind of knowledge pluralism I call standards pluralism. Put roughly, standards pluralism is the view that one never knows anything simpliciter. Rather, one knows by this-or-that epistemic standard. Because there is a plurality of epistemic standards, there is (...) a plurality of knowledge relations. In §1 I argue that one can construct an impressive case for standards pluralism. In §2 I clarify the relationship between standards pluralism, epistemic contextualism and epistemic relativism. In §3 I argue that standards pluralism faces a serious objection. The gist of the objection is that standards pluralism is incompatible with plausible claims about the normative role of knowledge. In §4 I finish by sketching the form that a standards pluralist response to this objection might take. (shrink)

Epistemic contextualists think that the extension of the expression ‘knows’ depends on and varies with the context of utterance. In the last 15 years or so this view has faced intense criticism. This paper focuses on two sorts of objections. The first are what I call the ‘linguistic objections’, which purport to show that the best available linguistic evidence suggests that ‘knows’ is not context-sensitive. The second is what I call the ‘disagreement problem’, which concerns the behaviour of ‘knows’ in (...) disagreement reports. These may not be the only objections to epistemic contextualism, but they are probably the most influential. I argue that the best current epistemic contextualist response to the linguistic objection is incomplete, and I show how it can be supplemented to deal with the full range of linguistic objections. I also develop a new solution to the disagreement problem. The upshot is that neither sort of objection gives us any reason to reject epistemic contextualism. This conclusion is, in a sense, negative—no new arguments for epistemic contextualism are advanced—but it’s a vital step towards rehabilitating the view. (shrink)

In order to make sense of collective doxastic reasons we need an account of group belief. Once we arrive at a more nuanced understanding of group belief it turns out that for some group beliefs we need not invoke collective epistemic reasons. However, we do need them for better understanding how and why different social identity groups will hold beliefs whose evidence-base is irreducibly social and tied to them being that kind of group. This short article is a commentary on (...) Veli Mitova's 2022 article "The collective epistemic reasons of social-identity groups". (shrink)

The target of this paper is the ‘simple’ knowledge account of assertion, according to which assertion is constituted by a single epistemic rule of the form ‘One must: assert p only if one knows p’. My aim is to argue that those who are attracted to a knowledge account of assertion should prefer what I call the ‘complex’ knowledge account, according to which assertion is constituted by a system of rules all of which are, taken together, constitutive of assertion. One (...) of those rules—which, following John Searle, I call the ‘preparatory condition’—is of the form ‘One must: assert p only if one knows p.’ All else being equal, simple accounts are preferable to complex accounts. I argue in this paper that all else isn't equal. While the simple knowledge account provides an elegant explanation of certain data, it is hard to see how to integrate the simple knowledge account into a more general theory of illocutionary acts. Because the complex knowledge account avoids this objection whil.. (shrink)

We use generic sentences like ‘Blondes are stupid’ to express stereotypes. But why is this? Does the fact that we use generic sentences to express stereotypes mean that stereotypes are themselves, in some sense, generic? I argue that they are. However, stereotypes are mental and generics linguistic, so how can stereotypes be generic? My answer is that stereotypes are generic in virtue of the beliefs they contain. Stereotypes about blondes being stupid contain a belief element, namely a belief that blondes (...) are stupid. This belief is an attitude taken towards the same proposition expressed by the sentence ‘Blondes are stupid’, hence why we use the latter to articulate the former. -/- This generic account of stereotypes can help us better understand their inner workings. I focus on one feature of generics, variability in the types of facts that can make them true, and argue that it can explain how stereotypes shape inferential patterns and thereby guide how we treat members of stereotyped groups. This feature, in turn, illuminates the harms caused by stereotyping and suggests some courses of action. (shrink)

Mona Simion’s Shifty Speech and Independent Thought argues for epistemic independence—the independence of good thinking from practical considerations. Along the way she argues against “shifty” views of knowledge and knowledge ascriptions, as well as against those who have tried to preserve the independence of knowledge from practical considerations by accepting shifty views of the epistemic normativity of assertion. In my discussion I start by highlighting some of Simion’s main claims and reconstructing her main lines of argument. I then raise some (...) minor concerns about her underlying methodology and some bigger picture concerns about her background theoretical assumptions and her argument for epistemic independence. (shrink)

Together we can achieve things that we could never do on our own. In fact, there are sheer endless opportunities for producing morally desirable outcomes together with others. Unsurprisingly, scholars have been finding the idea of collective moral obligations intriguing. Yet, there is little agreement among scholars on the nature of such obligations and on the extent to which their existence might force us to adjust existing theories of moral obligation. What interests me in this paper is the perspective of (...) the moral deliberating agent who faces a collective action problem, i.e. the type of reasoning she employs when deciding how to act. I hope to show that agents have collective obligations precisely when they are required to employ ‘we-reasoning’, a type of reasoning that differs from I-mode, best response reasoning, as I shall explain below. More precisely, two (or more) individual agents have a collective moral obligation to do x if x is an option for action that is only collectively available (more on that later) and each has sufficient reason to rank x highest out of the options available to them. (shrink)

The challenges facing us today require practical wisdom to allow us to react appropriately. In this paper, we argue that at a group level, we will make better decisions if we respect and take into account the moral judgment of agents with diverse styles of cognition and moral reasoning. We show this by focusing on the example of autism, highlighting different strengths and weaknesses of moral reasoning found in autistic and non-autistic persons respectively.

COVID-19 vaccine refusal seems like a paradigm case of irrationality. Vaccines are supposed to be the best way to get us out of the COVID-19 pandemic. And yet many people believe that they should not be vaccinated even though they are dissatisfied with the current situation. In this paper, we analyze COVID-19 vaccine refusal with the tools of contemporary philosophical theories of responsibility and rationality. The main outcome of this analysis is that many vaccine-refusers are responsible for the belief that (...) they should not be vaccinated and epistemically rational in holding it. This is an important result because it provides insights into the legitimacy of certain public health policies. In particular, this result shows that a public health policy that would abandon the project of convincing certain vaccine-refusers with reasons – e.g., by simply making vaccination compulsory – is prima facie illegitimate. (shrink)