L’α-foetoprotéine protège le cerveau femelle en développement des effets masculinisants et déféminisants des oestrogènes

peer reviewe

Reconsidering Prenatal Hormonal Influences on Human Sexual Orientation: Lessons from Animal Research.

peer reviewe

Evidence for a Role of Early Oestrogens in the Central Processing of Sexually Relevant Olfactory Cues in Female Mice

We previously found that female aromatase knockout (ArKO) mice showed less investigation of socially relevant odours as well as reduced sexual behaviour. We now ask whether these behavioural deficits might be due to an inadequate processing of odours in female ArKO mice. Therefore, we exposed female ArKO mice to same- and opposite-sex urinary odours and determined the expression of the immediate early gene c-Fos along the main and accessory olfactory projection pathways. We included ArKO males in the present study as we previously observed that they show female-typical detection thresholds of urinary odours, suggesting a role for perinatal oestrogens in these behavioural responses. No sex or genotype differences were observed in the olfactory bulb after urine exposure. By contrast, sex differences in c-Fos responses were observed in wild-type (WT) mice following exposure to male urine in the more central regions of the olfactory pathway; only WT females showed a significant Fos induction in the amygdala, central medial pre-optic area and ventromedial hypothalamus. However, ArKO females did not show a c-Fos response to male odours in the ventromedial hypothalamus, suggesting that the processing of male odours is affected in ArKO females and thus that oestrogens may be necessary for the development of neural responses to sexually relevant odours in female mice. By contrast, c-Fos responses to either male or oestrous female urine were very similar between ArKO and WT males, pointing to a central role of androgen vs. oestrogen signalling in the male circuits that control olfactory investigation and preferences

Sex differences in the neurokinin B system in the human infundibular nucleus.

CONTEXT: The recent report that loss-of-function mutations in either the gene encoding neurokinin B (NKB) or its receptor (NK3R) produce gonadotropin deficiencies in humans strongly points to NKB as a key regulator of GnRH release. OBJECTIVES: We used NKB immunohistochemistry on postmortem human brain tissue to determine: 1) whether the human NKB system in the infundibular nucleus (INF) is sexually dimorphic; 2) at what stage in development the infundibular NKB system would diverge between men and women; 3) whether this putative structural difference is reversed in male-to-female (MtF) transsexual people; and 4) whether menopause is accompanied by changes in infundibular NKB immunoreactivity. METHODS: NKB immunohistochemical staining was performed on postmortem hypothalamus material of both sexes from the infant/pubertal period into the elderly period and from MtF transsexuals. RESULTS: Quantitative analysis demonstrated that the human NKB system exhibits a robust female-dominant sexual dimorphism in the INF. During the first years after birth, both sexes displayed a moderate and equivalent level of NKB immunoreactivity in the INF. The adult features emerged progressively around puberty until adulthood, where the female-dominant sex difference appeared and continued into old age. In MtF transsexuals, a female-typical NKB immunoreactivity was observed. Finally, in postmenopausal women, there was a significant increase in NKB immunoreactivity compared to premenopausal women. CONCLUSION: Our results indicate that certain sex differences do not emerge until adulthood when activated by sex steroid hormones and the likely involvement of the human infundibular NKB system in the negative and positive feedback of estrogen on GnRH secretion

Alpha-fetoprotein protects the developing female mouse brain from masculinization and defeminization by estrogens

peer reviewe

Sexual differentiation of the brain and partner preference in the male rat

The studies reported in this thesis have been conducted to investigate the sexual differentiation of partner preference in the male rat. Initially, the effects of neonatal inhibition of brain estrogen formation on later coital behavior and partner preference of the male rat were studied. Later studies were directed to the central nervous system and investigated the neural mechanisms regulating male coital behavior and pattner preference. This first chapter provides an overview of the effects of gonadal hormones on the sexual differentiation of the brain, with emphasis on functional sex differences in behavior and neuroendocrine function in possible relation to morphological sex differences in the brain

Alpha-Fetoprotein: From a Diagnostic Biomarker to a Key Role in Female Fertility

Alpha-fetoprotein (AFP) is a well-known diagnostic biomarker used in medicine to detect fetal developmental anomalies such as neural tube defects or Down’s syndrome, or to follow up the development of tumors such as hepatocellular carcinomas. However, and despite the fact that the protein was discovered almost half a century ago, little was known about its physiological function. The study of Afp knock-out mice uncovered a surprising function of AFP: it is essential for female fertility and for expression of normal female behaviors, and this action is mediated through its estrogen binding capacity. AFP sequestrates estrogens and by so doing protects the female developing brain from deleterious (defeminizing/masculinizing) effects of these hormones

Support for Electronic Lab Notebooks at Top American Research Universities

Objective: Electronic Laboratory Notebooks (ELNs) are widely used in industry but little is known about their use in academia or the extent to which they are licensed or supported by research institutions or academic libraries. Methods: This paper describes an environmental scan conducted to determine whether major research institutions in the United States are providing enterprise ELN licenses to their users, which products they are licensing, and what role of the institutional library is playing in licensing and supporting ELNs. Results: Of the 35 universities included in our scan, 8 (23%) had an enterprise-wide license for an ELN and 10 (28%) provided some kind of support for ELNs. Of the 10 institutions that offered support for ELNs, 9 involved the library. A literature review revealed a number of barriers to adoption—from costs to the diversity of needs—that may be limiting the adoption of ELNs within research institutions. Conclusions: This research provides evidence about the current landscape of ELN support within academic institutions and the role of libraries in these initiatives

Alpha-fetoprotein controls female fertility and prenatal development of the gonadotropin-releasing hormone pathway through an antiestrogenic action

peer reviewedIt has been shown previously that female mice homozygous for an alpha-fetoprotein (AFP) null allele are sterile as a result of anovulation, probably due to a defect in the hypothalamic-pituitary axis. Here we show that these female mice exhibit specific anomalies in the expression of numerous genes in the pituitary, including genes involved in the gonadotropin-releasing hormone pathway, which are underexpressed. In the hypothalamus, the gonadotropin-releasing hormone gene, Gnrh1, was also found to be down-regulated. However, pituitary gene expression could be normalized and fertility could be rescued by blocking prenatal estrogen synthesis using an aromatase inhibitor. These results show that AFP protects the developing female brain from the adverse effects of prenatal estrogen exposure and clarify a long-running debate on the role of this fetal protein in brain sexual differentiation