Low dose prenatal testosterone exposure decreases the corticosterone response to stress in adult male, but not female, mice

Wilson, Hayley A.; Martin, Emily; Howes, Colin; Wasson, Cameron; Newman, Amy E. M.; Choleris, Elena; MacLusky, Neil J.

doi:10.1016/j.brainres.2019.146613

Cited by 6 publications

(4 citation statements)

References 60 publications

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“…Elevated prenatal testosterone alters placental androgen and estrogen receptor expression, as well as placental morphology (Sun and others 2012), including the placental vasculature, resulting in greater fetal hypoxia in males associated with alterations in the placental expression of genes involved in angiogenesis and blood vessel morphogenesis (Gopalakrishnan and others 2016). As we have recently reported, in mice even a relatively small prenatal increase in maternal testosterone levels has lasting sex-specific consequences for stress responses in the offspring (Wilson and others 2019). Prenatal stress, hypothyroidism and prenatal testosterone have all been reported to affect the placental inflammatory profile (Bronson and Bale 2014;Kelley and others 2018;Silva and others 2014).…”

Section: Discussionmentioning

confidence: 78%

Endocrine Insights into the Pathophysiology of Autism Spectrum Disorder

et al. 2020

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Autism spectrum disorder (ASD) is a class of neurodevelopmental disorders that affects males more frequently than females. Numerous genetic and environmental risk factors have been suggested to contribute to the development of ASD. However, no one factor can adequately explain either the frequency of the disorder or the male bias in its prevalence. Gonadal, thyroid, and glucocorticoid hormones all contribute to normal development of the brain, hence perturbations in either their patterns of secretion or their actions may constitute risk factors for ASD. Environmental factors may contribute to ASD etiology by influencing the development of neuroendocrine and neuroimmune systems during early life. Emerging evidence suggests that the placenta may be particularly important as a mediator of the actions of environmental and endocrine risk factors on the developing brain, with the male being particularly sensitive to these effects. Understanding how various risk factors integrate to influence neural development may facilitate a clearer understanding of the etiology of ASD.

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Section: Discussionmentioning

confidence: 78%

Endocrine Insights into the Pathophysiology of Autism Spectrum Disorder

et al. 2020

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“…We first addressed how GC-PC connectivity maps were established and structured during postnatal development (i.e., in a normal adaptive locomotor context). Since the motor apparatus and motor coordination undergo progressive adaptation, especially when animals open their eyes and start walking [52][53][54] , we assessed whether conserved connectivity maps observed in adults originate from a linear and progressive functional wiring. If connectivity maps reflect the strict establishment of the input/output relationships in a topographic manner, we expect to observe a corresponding structuration of the patchy microzonal organization.…”

Section: Network Connectivity Rules Mature During Developmentmentioning

confidence: 99%

“…Graph parameters allowed us to quantify and highlight significant changes in the graph encoding of synaptic maps, as modularity and participation dropped to minimal values indicating that modular structuration vanished at this stage before resuming to higher values in adulthood. Between P14-P18, mice start to walk and open their eyes 52,53,75 . They are hyperactive with bouts of vigorous jumping called 'hoppy' or 'popcorn'…”

Section: Graph Network Identified a Critical Periodmentioning

confidence: 99%

Cerebellar connectivity maps embody individual adaptive behavior

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Bahuguna

Gagneux

et al. 2021

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From planification to execution, cerebellar microcircuits encode different features of skilled movements. However, it is unknown whether cerebellar synaptic connectivity maps encode movement features in a motor context specific manner. Here we investigated the spatial organization of excitatory synaptic connectivity in mice cerebellar cortex in different locomotor contexts: during development and in normal, trained or altered locomotor conditions. We combined optical, electrophysiological and graph modelling approaches to describe synaptic connectivity between granule cells (GCs) and Purkinje cells (PCs). Synaptic map maturation during development revealed a critical period in juvenile animals before the establishment of a stereotyped functional organization in adults. However, different locomotor conditions lead to specific GC-PC connectivity maps in PCs. Ultimately, we demonstrated that the variability in connectivity maps directly accounts for individual specific behavioral features of mice locomotion, suggesting that GC-PC networks encode a general motor context as well as individual specific internal models underlying motor adaptation.

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“…In addition, neonatal gonadectomy in males “feminizes” HPA response and increases mineralocorticoid receptor binding in the pituitary (Mccormick et al, 1998 ) since deprivation of testosterone and E2 during perinatal periods increase corticosterone levels to female levels. Moreover, when low doses of testosterone are administrated perinatally, the effects on development and reproduction were no different, but corticosterone level in adulthood during stress response was significantly decreased in males (Wilson et al, 2020 ). In light of these data, organizational action of estrogens and androgens on the establishment of the pituitary and adrenal neuroendocrine systems in the adult male and female animals can be postulated.…”

Section: Introductionmentioning

confidence: 99%

Organizational Effects of Estrogens and Androgens on Estrogen and Androgen Receptor Expression in Pituitary and Adrenal Glands in Adult Male and Female Rats

et al. 2022

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Sex steroid hormones, such as androgens and estrogens, are known to exert organizational action at perinatal periods and activational effects during adulthood on the brain and peripheral tissues. These organizational effects are essential for the establishment of biological axes responsible for regulating behaviors, such as reproduction, stress, and emotional responses. Estradiol (E2), testosterone, and their metabolites exert their biological action through genomic and non-genomic mechanisms, bounding to canonical receptors, such as estrogen receptor (ER)α, ERβ, and androgen receptor (AR) or membrane receptors, such as the G protein-coupled estrogen receptor (GPER), respectively. Expression of ERs and AR was found to be different between males and females both in the brain and peripheral tissues, suggesting a sex-dependent regulation of their expression and function. Therefore, studying the ERs and AR distribution and expression levels is key to understand the central and peripheral role of sex steroids in the establishment of sex-specific behaviors in males and females. We investigated the organizational effects of estrogens and androgens in the pituitary and adrenal glands of adult male and female rats. For this, selective blockade of AR with flutamide or 5α-reductase with finasteride or aromatase with letrozole during the first 5 days of life has been performed in male and female pups and then quantification of ERs and AR expression in both glands has been carried out in adulthood. Data show that inhibition of dihydrotestosterone (DHT) and E2 production during the first five postnatal days mainly decreases the ER expression in male to female values and AR expression in female to male levels in the pituitary gland and increases AR expression in female to male levels in the adrenal gland. In contrast, blocking the action of androgens differentially modulates the ERs in males and females and decreases AR in both males and females in both glands. Altogether, the results suggest that neonatal modifications of the androgen and estrogen pathways can potentially lead to permanent modifications of the neuroendocrine functions of the pituitary and adrenal glands in the adulthood of both sexes.

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Low dose prenatal testosterone exposure decreases the corticosterone response to stress in adult male, but not female, mice

Cited by 6 publications

References 60 publications

Endocrine Insights into the Pathophysiology of Autism Spectrum Disorder

Endocrine Insights into the Pathophysiology of Autism Spectrum Disorder

Cerebellar connectivity maps embody individual adaptive behavior

Organizational Effects of Estrogens and Androgens on Estrogen and Androgen Receptor Expression in Pituitary and Adrenal Glands in Adult Male and Female Rats

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