Absence of Gonadotropin-Releasing Hormone 1 and Kiss1 Activation in α-Fetoprotein Knockout Mice: Prenatal Estrogens Defeminize the Potential to Show Preovulatory Luteinizing Hormone Surges

González-Martı́nez, David; Mees, Christelle De; Douhard, Quentin; Szpirer, Claude; Bakker, Julie

doi:10.1210/en.2007-1422

Cited by 60 publications

(65 citation statements)

References 33 publications

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“…By contrast, AfpKO females did not show a female-typical Fos response to male odors in forebrain areas involved in reproduction (AVPV, PeN, mPOA, and BSTpm), suggesting that the processing of sex-related olfactory cues is defeminized in AfpKO females. These results fully support previous findings showing that exposure to prenatal estradiol defeminized the potential to show lordosis behavior (16), male-directed mate preferences (17), and the ability to show a steroid-induced preovulatory LH surge (19) in adulthood. Our results suggest that these deficits might reflect an inability to transduce adequately sex-related olfactory cues into signals that will initiate and modulate reproductive behavioral and/or endocrine changes.…”

supporting

confidence: 91%

“…As previously demonstrated (19), the number of kisspeptin-ir neurons in the AVPV/PeN of AfpKO female mice was dramatically reduced compared with their WT littermates (Table 4 and comparison of Figure 4, A-C, for illustration). This was confirmed by a two-way ANOVA revealing a significant effect of genotype (F (1,27) ϭ 107.9116, P Ͻ .0001), bedding (F (1,27) ϭ 15.0107, P Ͻ .001), and a nearly significant interaction between these 2 factors (F (1,27) ϭ 4.1683, P ϭ .0511).…”

Section: Effect Of Bedding Exposure On Fos Expression In Kisspeptin Nsupporting

confidence: 74%

“…In order to analyze the role of prenatal estradiol on the sexually dimorphic processing of pheromones, we used female mice deficient in ␣-fetoprotein (AfpKO), which lack the protective actions of Afp against maternal estradiol. AfpKO females are clearly defeminized with regards to their sexual behavior, ie, lordosis behavior (16) and male-directed mate preference (17) as well as their GnRH/kisspeptin system, ie, no hormonally induced LH surges (18,19). Because olfaction plays a pivotal role in mate recognition in mice (20), the reproductive deficit observed in AfpKO females might thus reflect an inability to respond to male odors and/or an inadequate processing by the neuroendocrine system.…”

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confidence: 99%

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Absence of Female-Typical Pheromone-Induced Hypothalamic Neural Responses and Kisspeptin Neuronal Activity in α-Fetoprotein Knockout Female Mice

Taziaux

Bakker

2015

Endocrinology

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Pheromones induce sexually dimorphic neuroendocrine responses, such as LH secretion. However, the neuronal network by which pheromones are converted into signals that will initiate and modulate endocrine changes remains unclear. We asked whether 2 sexually dimorphic populations in the anteroventral periventricular and periventricular nuclei that express kisspeptin and tyrosine hydroxylase (TH) are potential candidates that will transduce the olfactory signal to the neuroendocrine system. Furthermore, we assessed whether this transduction is sensitive to perinatal actions of estradiol by using female mice deficient in α-fetoprotein (AfpKO), which lack the protective actions of Afp against maternal estradiol. Wild-type (WT) and AfpKO male and female mice were exposed to same- versus opposite-sex odors and the expression of Fos (the protein product of the immediate early gene c-Fos) was analyzed along the olfactory projection pathways as well as whether kisspeptin, TH, and GnRH neurons are responsive to opposite-sex odors. Male odors induced a female-typical Fos expression in target forebrain sites of olfactory inputs involved in reproduction in WT, but not in AfpKO females, whereas female odors induced a male-typical Fos expression in males of both genotypes. In WT females, opposite-sex odors induced Fos in kisspeptin and TH neurons, whereas in AfpKO females and WT males, only a lower, but still significant, Fos expression was observed in TH but not in kisspeptin neurons. Finally, opposite-sex odors did not induce any significant Fos expression in GnRH neurons of both sexes or genotypes. Our results strongly suggest a role for fetal estrogen in the sexual differentiation of neural responses to sex-related olfactory cues.

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supporting

confidence: 91%

Section: Effect Of Bedding Exposure On Fos Expression In Kisspeptin Nsupporting

confidence: 74%

mentioning

confidence: 99%

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Absence of Female-Typical Pheromone-Induced Hypothalamic Neural Responses and Kisspeptin Neuronal Activity in α-Fetoprotein Knockout Female Mice

Taziaux

Bakker

2015

Endocrinology

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“…We observed no increase in the number of calbindin immunoreactive neurons, a sexually dimorphic population highly sensitive to the masculinizing effects of perinatal E 2 . The number of kisspeptin cells in the RP3V, a neuronal population normally reduced by perinatal E 2 (Kauffman et al 2007, González-Martínez et al 2008, was even higher in BPAexposed individuals. These data indicate that during the perinatal period, when endogenous ovarian estrogens are undetectable and exogenous estrogens have limited brain access (due to their binding to a-fetoprotein), BPA at reference doses was unable to mimic the masculinizing and defeminizing effects of perinatal E 2 on the reproductive functions and behaviors in female mice.…”

Section: Discussionmentioning

confidence: 90%

Neuroendocrine and behavioral effects of maternal exposure to oral bisphenol A in female mice

Naulé¹,

Picot²,

Martini³

et al. 2014

Journal of Endocrinology

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Bisphenol A (BPA) is a widespread estrogenic compound. We investigated the effects of maternal exposure to BPA at reference doses on sexual behavior and neuroendocrine functions of female offspring in C57BL/6J mice. The dams were orally exposed to vehicle alone or vehicle-containing BPA at doses equivalent to the no observed adverse effect level (5 mg/kg body weight per day) and tolerable daily intake (TDI, 0.05 mg/kg body weight per day) level from gestational day 15 until weaning. Developmental exposure to BPA increased the lordosis quotient in naive females exposed to BPA at the TDI dose only. BPA exposure had no effect on olfactory preference, ability to express masculine behaviors or number of calbindin-positive cells, a sexually dimorphic population of the preoptic area. BPA at both doses selectively increased kisspeptin cell number in the preoptic periventricular nucleus of the rostral periventricular area of the third ventricle in adult females. It did not affect the number of GNRH-positive cells or percentage of kisspeptin appositions on GNRH neurons in the preoptic area. These changes were associated with higher levels of estradiol (E 2 ) at the TDI dose while levels of LH, estrus cyclicity, ovarian and uterine weights, and fertility remained unaffected. Delay in the time of vaginal opening was observed during the postnatal period at TDI dose, without any alteration in body growth. This shows that developmental exposure to BPA at reference doses did not masculinize and defeminize the neural circuitry underlying sexual behavior in female mice. The TDI dose specifically exacerbated responses normally induced by ovarian E 2 , through estrogen receptor a, during the postnatal/prepubertal period.

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“…Female rat and mouse brains are protected from these processes because there is no perinatal gonadal androgen secretion and because the developing brain is protected from maternal estrogens by ␣-fetoprotein, which binds estrogens to create a complex that does not cross the placenta. The importance of ␣-fetoprotein is underscored by demonstrations by Bakker and her colleagues (33,279) that 1) the brains and reproductive behavior of female transgenic mice that do not express ␣-fetoprotein were masculinized and defeminized with testosterone treatment, and 2) that the feminine phenotype was rescued by blocking embryonic metabolism of testosterone with an aromatase inhibitor. In humans, ␣-fetoprotein is abundant, but does not bind estrogens.…”

Section: Physiological Sex Differences In Disordered Eating)mentioning

confidence: 99%

Sex differences in the physiology of eating

Asarian

Geary²

2013

American Journal of Physiology-Regulatory, Integrative and Comp

408

349

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(HPG) axis function fundamentally affects the physiology of eating. We review sex differences in the physiological and pathophysiological controls of amounts eaten in rats, mice, monkeys, and humans. These controls result from interactions among genetic effects, organizational effects of reproductive hormones (i.e., permanent early developmental effects), and activational effects of these hormones (i.e., effects dependent on hormone levels). Male-female sex differences in the physiology of eating involve both organizational and activational effects of androgens and estrogens. An activational effect of estrogens decreases eating 1) during the periovulatory period of the ovarian cycle in rats, mice, monkeys, and women and 2) tonically between puberty and reproductive senescence or ovariectomy in rats and monkeys, sometimes in mice, and possibly in women. Estrogens acting on estrogen receptor-␣ (ER␣) in the caudal medial nucleus of the solitary tract appear to mediate these effects in rats. Androgens, prolactin, and other reproductive hormones also affect eating in rats. Sex differences in eating are mediated by alterations in orosensory capacity and hedonics, gastric mechanoreception, ghrelin, CCK, glucagon-like peptide-1 (GLP-1), glucagon, insulin, amylin, apolipoprotein A-IV, fatty-acid oxidation, and leptin. The control of eating by central neurochemical signaling via serotonin, MSH, neuropeptide Y, Agouti-related peptide (AgRP), melanin-concentrating hormone, and dopamine is modulated by HPG function. Finally, sex differences in the physiology of eating may contribute to human obesity, anorexia nervosa, and binge eating. The variety and physiological importance of what has been learned so far warrant intensifying basic, translational, and clinical research on sex differences in eating.neuroendocrinology; estrogens; testosterone; eating disorders; obesity SEX DIFFERENCES ARE PERVASIVE in physiology and medicine (51,64,73,109,110,466,797,826). The controls of eating and energy homeostasis are no exceptions. It was observed approximately 100 years ago that removal of the ovaries leads to marked accretion of adipose tissue in rats (697), that daily food intake expressed as kilocalories per gram body weight differs between male and female rats (778), and that food intake varies regularly through the ovarian cycle in intact female rats (674, 779). Sex differences in eating have been the subject of physiological research ever since. The clinical relevance of this work is increasingly evident. In the United States, women are approximately threefold more vulnerable than men to psychiatric eating disorders (346,351) and approximately twofold more vulnerable to severe and morbid obesity (BMI Ն 35 and 40 kg/m 2 , respectively, mass/height 2 ) (226). Women also appear to suffer more from these disorders in terms of physical and psychological functioning and quality of life (24,84,273,292,465,531,762). The increased obesity burden suffered by women is reflected in the fact that Ͼ80% of bariatric surgery patients in the U...

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Absence of Gonadotropin-Releasing Hormone 1 and Kiss1 Activation in α-Fetoprotein Knockout Mice: Prenatal Estrogens Defeminize the Potential to Show Preovulatory Luteinizing Hormone Surges

Cited by 60 publications

References 33 publications

Absence of Female-Typical Pheromone-Induced Hypothalamic Neural Responses and Kisspeptin Neuronal Activity in α-Fetoprotein Knockout Female Mice

Absence of Female-Typical Pheromone-Induced Hypothalamic Neural Responses and Kisspeptin Neuronal Activity in α-Fetoprotein Knockout Female Mice

Neuroendocrine and behavioral effects of maternal exposure to oral bisphenol A in female mice

Sex differences in the physiology of eating

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