Engaging the question of postmodern ethical intersubjectivity in the work of Emmanuel Levinas and Luce Irigaray I attempt to move beyond Levinas sacrificial view of intersubjectivity with Irigaray's critique of sexual difference. I argue that Levinas view of ethical 'subjectivity' is violently conditioned by a necessary narcissim located in Levinas's description of the feminine dwelling. Instead of narcissim I argue with Irigaray for a way of love that offers an ethical relationship bonded in mutuality. This way of love is rooted in an understanding of the primordial matter of life as good for intersubjective-relationships that do not depend upon narcissim for connection. Concluding this study I suggest that his kind of intersubjectivity can be rooted in a primordial way of life found in the rhythm of breath.

La connaissance et la maîtrise du déterminisme du sexe et de la différenciation sont des défis majeurs pour la production de tilapia. L'élevage de populations monosexes mâles évite les effets négatifs d'une reproduction continue et profite de la meilleure croissance des mâles. Dans le contexte d'une aquaculture durable, le développement de stratégies alternatives et écologiques est nécessaire pour le contrôle du sexe du tilapia sans avoir recours aux approches hormonales. Ces alternatives reposent sur des approches génétiques ou environnementales, en utilisant l'effet masculinisant des températures élevées appliquées au cours de la différenciation sexuelle. Dans cette thèse la recherche de gènes impliqués dans la différenciation sexuelle a été réalisée dans les gonades et le cerveau en utilisant l'analyse de certains gènes candidats. L'objectif était de développer des marqueurs putatifs pour produire des populations monosexes mâles par des approches respectueuses des consommateurs et de l'environnement. Les expressions temporelles et spatiales de cyp19a1a, cyp19a1b, FOXL2, dmrt1, SOX9, DAX1 et amh ont été analysées dans plusieurs descendances de mâles ou des femelles génétiques ainsi que dans des femelles traitées à fortes températures. Leur lien avec les masculinisations par la températ ure a également été recherché sur des lignées thermosensibles de tilapia. L'un des gènes qui présente un dimorphisme sexuel important est l'amh qui est exprimé aussi bien dans les gonades que dans le cerveau pendant les premiers stades de la différenciation sexuelle. Le niveau d'expression de l'amh dans le cerveau est élevé chez les mâles quand les gonades sont toujours indifférenciées et probablement même avant la synthèse des stéroïdes gonadique. Une procédure de sexage moléculaire précoce a été développée en utilisant ce gène chez le tilapia. Cette procédure sera d'un grand intérêt pour les éleveurs et les scientifiques pour identifier rapidement des individus YY mâles avec un gain en temps et en argent, et pourra être utilisée également pour rechercher d'autres approches fiables de production de populations monosexes mâles sans l'utilisation des hormones. / Knowledge and the control of sex determination and differentiation are major challenges for tilapia production. Farming of male monosex populations avoids the negative effects of a continuous reproduction and benefits from males' fast growth. In the context of a sustainable aquaculture, alternative and ecological strategies have to be developed to control sex in tilapia without hormonal treatment. These approaches will rely on genetic and environmental treatments, such as the use of masculinising high temperatures applied during sex differentiation. The search for genes implicated in sex differentiation has been performed in both gonads and brains using the analysis of candidate genes. The objective was to develop putative markers to produce male monosex populations through consumer and environmentally friendly approaches. Temporal and organ expressions of cyp19a1a, cyp19a1b, foxl2, dmrt1, sox9, dax1 and amh were analysed in several progenies o f genetic males or females as well as in temperature-treated individuals. Their link with temperature masculinisation was also performed on the thermosensitive tilapia lines. One of the sexual dimorphic genes was amh which was found expressed in both gonads and brains during early stages of sex-differentiation. Brain amh was elevated in males when the gonads were still undifferentiated and probably before steroid synthesis took place. A precocious molecular sexing procedure was developed in tilapia using this gene. This procedure will be of great advantage for both farmers and scientists in identifying quickly male individuals and in finding reliable male monosex approaches not using hormones.

Orientador: Rafael Henrique Nóbrega / Resumo: A decisão sobre se uma gônada bipotencial se desenvolverá em um testículo ou em um ovário é considerado um estágio crítico na diferenciação sexual dos vertebrados. A administração de esteróides exógenos durante este período pode afetar essa plasticidade, promovendo a diferenciação sexual na direção feminina ou masculina. Dessa forma, o objetivo desta tese foi avaliar os efeitos do tratamento de 17β-estradiol no desenvolvimento de Astyanax altiparanae (lambari), através de análises histológicas e de análises de expressão genica de possíveis genes envolvidos em vias masculinas e femininas. Para isso, larvas com gônadas indiferenciadas foram alimentadas com Artemia contendo diferentes concentrações de estradiol durante 28 dias, desde o 1 dia pós-eclosão (dpe) até o período que precede a diferenciação gonadal. Nossos resultados mostraram que o E2 modificou o fenotípo e a relação sexual histológica e, surpreendentemente, induziu intersexo com com a presença de óvulos nos testículos nas concentrações de 2 e 6 mg de E2/kg de alimento. Esses dados são uma evidência clara de que o tratamento utilizado não foi suficiente para induzir a reversão completa do sexo em A. altiparanae. Em termos de expressão gênica, o tratamento com E2 (6 mg/kg de alimento) produziu uma notável plasticidade gonadal entre machos e fêmeas aos 90 dias após a eclosão (dph). Os machos, denominados “machos resistentes ao estradiol”, superexpressaram os genes masculinos, como dmrt1, sox9 e amh. Dessa forma, nó... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The decision whether a bipotential gonad will become a testis or ovary is considered a critical stage in vertebrate sex determination. Administration of exogenous steroids can affect this plasticity by skewing the sex gonadal differentiation towards a male or female. The aim of this study is to evaluate the effects of 17β-estradiol (E2) diet on Astyanax altiparanae (lambari) development, focusing on the gonadal development and gene expression analysis of possible candidate genes involved in either male or female pathways. Larvae with undifferentiated gonads were fed with steroid diet containing different concentrations of E2 during 28 days, from the mouth opening until a period that precedes the gonadal differentiation. Animals were sampled at 90 days post-hatching (dhp) for histology and gene expression analysis. Our results showed that E2 disrupted both phenotypic and histological sex ratios, and surprisingly, induced intersex with testis-ova in the concentrations of 2 and 6 mg E2/Kg food. This data is a clear evidence that the treatment used was not enough to induce complete sex reversal in A. altiparanae. However, in terms of gene expression, E2 (6mg/Kg food) induced a remarkable gonadal plasticity between males and females at 90 dph. The males, named as E2 resistant males, overexpressed the male-biased genes, such as dmrt1, sox9 and amh. We suggested that these males were able to resist the E2-induced feminization by the expression of genes related to testis differentiat... (Complete abstract click electronic access below) / Doutor

No description available.

Graduation date: 1995

Sexual maturation and sex differentiation comprise facets of a common theme: reproduction. The endocrine system regulates many of the critical physiological processes necessary for reproduction and offers a framework within which technologies can be developed for controlling sexual maturation and sex differentiation. The studies described in this thesis were undertaken to improve the understanding of the endocrine control of these critical stages of development in salmonids. Final ovarian maturation in salmon is accompanied by dynamic changes in plasma hormone levels. Ovulation can be accelerated through the use of hormones such as gonadotropin releasing hormone or its analogs (GnRHa). The effectiveness of GnRHa often depends on the timing of treatment. To determine if plasma concentrations of steroids can be used to predict the sensitivity of adult female coho salmon (Oncorhynchus kisutch) to GnRHa, circulating levels of testosterone, 17α,20β-dihydroxyprogesterone (DHP), and estradiol were measured before and after injection with GnRHa to accelerate ovulation. We found that high levels of testosterone were predictive of early response of coho salmon to GnRHa treatment. The correlation between testosterone and ovulatory response to GnRHa suggested a possible functional relation. However. implantation or injection of testosterone. 17α-methyltestosterone (MT), or the antiandrogen, cyproterone acetate (CA), before or with GnRHa treatment did not affect the ovulatory response of coho or chinook salmon ( 0. tshawytscha) to GnRHa. Chinook salmon treated with MT alone had accelerated ovulation in comparison to controls. If steroids are involved in sex differentiation. steroids must be produced early in development. In vitro production of steroids in both coho salmon and rainbow trout (0. mykiss) was assessed from hatch through sex differentiation. Cortisol, androstenedione, testosterone, and estradiol were produced just after hatching by tissue explants that contained anterior kidneys and gonads of coho salmon. To circumvent the problem of not knowing the sex of individuals until after sex differentiation, single-sex populations of rainbow trout were produced by gynogenesis or androgenesis. Tissue explants produced more androstenedione than testosterone or estradiol. More androgens were produced by testes and more estradiol was produced by ovaries within 6 to 10 weeks of hatching. Dietary treatment with estradiol or MT inhibited gonadal steroid secretion. Electrophoresis of gonadal homogenates from salmonids revealed several sex-specific bands. In particular, a prominent band of about 50,000 daltons was apparent in ovaries but not testes. Production of sex-specific proteins may be affected by dietary steroid treatment. / Graduation date: 1991

No description available.

Three point mutations have been found in the hormone-binding domain (HBD) of the human androgen receptor (hAR): one in the N-terminal end (Ile663Asn in a family with partial androgen insensitivity syndrome (PAIS)); one in the middle, (Leu820Val in a family with PAIS); and one in the C-terminal end (Pro903Ser, in a family with complete AIS). The positions 663 and 903 were the most terminal mutation sites in the HBD found to date. The three mutant hARs have been previously characterized biochemically in genital skin fibroblasts. In the family with the Leu820Val substitution, the mother and the grandmother were found to be carriers for the same mutation. To prove their pathogenicity, each of the three mutations has been reproduced in an hAR expression vector that was transfected into COS-1 cells. In COS-1 cells, the complexes from Pro903Ser and Leu820Val had: increased thermolability; increased dissociation rates; decreased affinity; and abnormal transactivation. There was a hierarchy in the severity of the mutations expressed in kinetic and transactivation assays that correlated with the severity of the clinical phenotype. The pathogenicity of the Pro903Ser and the Leu820Val mutations was thereby confirmed. In COS-1 cells, the AR with Ile663Asn had normal thermolability, normal dissociation rates, and normal transactivation, but a decreased affinity. Although this sequence alteration has only been found in a PAIS patient, its pathogenicity is not considered to be proven. More sensitive assays are needed for this purpose.

The sex-determining gene on the Y chromosome, named Sry, initiates differentiation of gonadal somatic cells into testes, which in turn regulate the development of male phenotype. / The B6.YTIR sex-reversed mouse provides a good model for studying sex-determining mechanisms. We proposed a hypothesis that the testis-determining pathway is impaired downstream of Sry transcription in the B6.YTIR fetus. / The current study aimed to determine the hierarchical order of Sry, Sox9, Pn1, and Mis by examining their expression in B6.YTIR gonads as compared to normal B6.XY gonads by RT-PCR. / Results. Sry expression was comparable between B6.Y TIR and B6.XY gonads, with its onset between 10.5 and 11.5 dpc, a peak at 11.5 dpc, and downregulation thereafter. Sox9 expression was detectable in both B6.XX and B6.XY gonads at 11.5 dpc at comparable levels, but was then downregulated in B6.XX gonads at 12.5 dpc, by which stage testicular cord formation had began in B6.XY gonads. Pn1 was expressed in both B6.XX and B6.XY gonads at comparable levels at 11.5 dpc and was upregulated in B6.XY gonads at 12.5dpc. Mis expression in B6.Y TIR gonads was low at 10.5 and 11.5 dpc with a peak at 12.5dpc and higher levels only in ovotestes at 14.5dpc. / These results indicate that all Sox9, Pn1, and MIS genes follow a sexually dimorphic pattern of expression associated with development of testicular cords. Therefore, these genes are placed downstream of Sry in the fetal mouse gonad. Furthermore, we conclude that the testis-determining pathway is impaired upstream of Sox9 and Pn1 and Mis in the B6.YTIR gonad. (Abstract shortened by UMI.)

The human androgen receptor (hAR) is a ligand-activated, nuclear transcription factor. Mutations affecting the formation and/or action of the hAR cause androgen insensitivity syndrome (AIS). The majority of mutations identified to date are within the DNA- and hormone-binding domains; very few have been identified in the transactivational modulatory domain, encoded by exon 1. This work presents an analysis of exon 1 and the 5$ sp prime$-flanking region of the hAR in a set of subjects whose AIS was believed to be caused by a mutation within these regions. Six of twelve strains had a nonsense or frameshift mutation in exon 1; a seventh strain had two missense and one silent substitution; no mutations were identified in the remaining subjects. The two missense mutations were recreated, individually and together, in an hAR complementary DNA (cDNA) expression vector and expressed in heterologous COS-1 cells. Their pathogenicity could not be proven with the system and assays used. In addition, mRNA and protein levels were analyzed and correlated with the identified mutations and the subjects' phenotype.