Defining the Role of Estrogen Receptor ? in the Regulation of Female Fertility.

ABSTRACT: Estrogens are essential hormones for the regulation of fertility. Cellular responses to estrogens are mediated by estrogen receptor ? (ESR1) and estrogen receptor ? (ESR2). In mouse and rat models, disruption of Esr1 causes infertility in both males and females. However, the role of ESR2 in reproductive function remains undecided because of a wide variation in phenotypic observations among Esr2-mutant mouse strains. Regulatory pathways independent of ESR2 binding to its cognate DNA response element have also been implicated in ESR2 signaling. To clarify the regulatory roles of ESR2, we generated two mutant rat models: one with a null mutation (exon 3 deletion, Esr2?E3) and the other with an inframe deletion selectively disrupting the DNA binding domain (exon 4 deletion, Esr2?E4). In both models, we observed that ESR2-mutant males were fertile. ESR2-mutant females exhibited regular estrous cycles and could be inseminated by wild-type (WT) males but did not become pregnant or pseudopregnant. Esr2-mutant ovaries were small and differed from WT ovaries by their absence of corpora lutea, despite the presence of follicles at various stages of development. Esr2?E3- and Esr2?E4-mutant females exhibited attenuated preovulatory gonadotropin surges and did not ovulate in response to a gonadotropin regimen effective in WT rats. Similarities of reproductive deficits in Esr2?E3 and Esr2?E4 mutants suggest that DNA binding-dependent transcriptional function of ESR2 is critical for preovulatory follicle maturation and ovulation. Overall, the findings indicate that neuroendocrine and ovarian deficits are linked to infertility observed in Esr2-mutant rats.

SUBMITTER: Rumi MAK 

PROVIDER: S-EPMC5505218 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature