RGD Reference Report - Defining the Role of Estrogen Receptor β in the Regulation of Female Fertility. - Rat Genome Database

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

Authors: Rumi, M A Karim  Singh, Prabhakar  Roby, Katherine F  Zhao, Xiao  Iqbal, Khursheed  Ratri, Anamika  Lei, Tianhua  Cui, Wei  Borosha, Shaon  Dhakal, Pramod  Kubota, Kaiyu  Chakraborty, Damayanti  Vivian, Jay L  Wolfe, Michael W  Soares, Michael J 
Citation: Rumi MAK, etal., Endocrinology. 2017 Jul 1;158(7):2330-2343. doi: 10.1210/en.2016-1916.
RGD ID: 38548924
Pubmed: PMID:28520870   (View Abstract at PubMed)
PMCID: PMC5505218   (View Article at PubMed Central)
DOI: DOI:10.1210/en.2016-1916   (Journal Full-text)

Estrogens are essential hormones for the regulation of fertility. Cellular responses to estrogens are mediated by estrogen receptor α (ESR1) and estrogen receptor β (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, Esr2ΔE3) and the other with an inframe deletion selectively disrupting the DNA binding domain (exon 4 deletion, Esr2ΔE4). 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. Esr2ΔE3- and Esr2ΔE4-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 Esr2ΔE3 and Esr2ΔE4 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Female Infertility  ISOEsr2 (Rattus norvegicus)38548924; 38548924 RGD 
Female Infertility  IMP 38548924; 38548924; 38548924; 38548924 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Objects Annotated

Genes (Rattus norvegicus)
Esr2  (estrogen receptor 2)
Esr2em1Soar  (estrogen receptor 2; ZFN induced mutant 1, Soar)

Genes (Mus musculus)
Esr2  (estrogen receptor 2 (beta))

Genes (Homo sapiens)
ESR2  (estrogen receptor 2)

SD-Esr2em1Soar  (NA)
SD-Esr2em2Soar  (NA)

Additional Information