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Deletion of neural estrogen receptor alpha induces sex differential effects on reproductive behavior in mice.

ABSTRACT: Estrogen receptor (ER) α is involved in several estrogen-modulated neural and peripheral functions. To determine its role in the expression of female and male reproductive behavior, a mouse line lacking the ERα in the nervous system was generated. Mutant females did not exhibit sexual behavior despite normal olfactory preference, and had a reduced number of progesterone receptor-immunoreactive neurons in the ventromedial hypothalamus. Mutant males displayed a moderately impaired sexual behavior and unaffected fertility, despite evidences of altered organization of sexually dimorphic populations in the preoptic area. In comparison, males deleted for both neural ERα and androgen receptor (AR) displayed greater sexual deficiencies. Thus, these data highlight a predominant role for neural ERα in females and a complementary role with the AR in males in the regulation of sexual behavior, and provide a solid background for future analyses of neuronal versus glial implication of these signaling pathways in both sexes.

SUBMITTER: Trouillet AC

PROVIDER: S-EPMC9021208 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Deletion of neural estrogen receptor alpha induces sex differential effects on reproductive behavior in mice.

Trouillet Anne-Charlotte AC Ducroq Suzanne S Naulé Lydie L Capela Daphné D Parmentier Caroline C Radovick Sally S Hardin-Pouzet Hélène H Mhaouty-Kodja Sakina S

Communications biology 20220420 1

Estrogen receptor (ER) α is involved in several estrogen-modulated neural and peripheral functions. To determine its role in the expression of female and male reproductive behavior, a mouse line lacking the ERα in the nervous system was generated. Mutant females did not exhibit sexual behavior despite normal olfactory preference, and had a reduced number of progesterone receptor-immunoreactive neurons in the ventromedial hypothalamus. Mutant males displayed a moderately impaired sexual behavior ...[more]

PMID: 35444217

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Project description:Previous studies have demonstrated that prior reproductive experience can influence anxiety-like behaviors, although neural mechanisms underlying this shift remain unknown. Studies in virgin females suggest that activation of the two estrogen receptor subtypes, ERα and ERβ, have differing effects on anxiety. Specifically, ERβ activation has been shown to reduce anxiety-like behaviors, while ERα activation has no significant effect. The purpose of the present study was to examine the possible roles of ERα and ERβ subtypes in parity-induced alterations in anxiety-like behavior, as tested on the elevated plus maze (EPM). Groups of ovariectomized, age-matched, nulliparous and primiparous females were tested on the EPM following administration of the ERα agonist 4,4',4''-(4-Propyl-{1H}-pyrazole-1,3,5-tryl)trisphenol (PPT; 1 mg/kg), the ERβ agonist Diarylpropionitrile (DPN; 1 mg/kg) or vehicle (DMSO). All drugs were administered once daily for 4 days prior to testing as this dosing paradigm has previously been used to demonstrate anxiolytic effects of DPN in virgin rats. In addition, as exposure to the EPM is a psychological stressor, physiological markers of the stress response were measured in both plasma (corticosterone) and brain (corticotropin releasing hormone; CRH) post-EPM testing. Unexpectedly, the ERα agonist PPT selectively increased the time spent exploring the open arms of the EPM in non-lactating, primiparous females, with no significant effects of DPN observed in either nulliparous or primiparous subjects. All females administered PPT and tested on the EPM demonstrated significantly reduced corticosterone secretion when compared to vehicle-treated controls. In addition, significant effects of both reproductive experience and PPT administration on CRH mRNA expression were observed in both the paraventricular nucleus and amygdala using qPCR. These findings indicate that reproductive experience modulates the effects of ERα activation on both EPM behavior related to anxiety and CRH gene expression.

Dataset Information

Deletion of neural estrogen receptor alpha induces sex differential effects on reproductive behavior in mice.

Publications

Deletion of neural estrogen receptor alpha induces sex differential effects on reproductive behavior in mice.

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