Uterine development and fertility are dependent on gene dosage of the nuclear receptor coregulator REA.

Endocrinology
Sunghee ParkBenita S Katzenellenbogen

Abstract

Although the effectiveness of nuclear hormone-receptor complexes is known to depend on coregulator partner proteins, relatively little is known about the roles of coregulators in uterine development and early stages of pregnancy and implantation. Because conventional genetic deletion of the coregulator, repressor of estrogen receptor activity (REA), was embryonic lethal, we here study REA conditional knockout mice generated by cre-loxP recombination, in which REA function was abrogated only in progesterone receptor-expressing tissues, to define the roles of REA in postembryonic stages and in a tissue-specific manner. We find that REA has gene dose-dependent activity impacting uterine development and fertility. Conditional homozygous mutant (REA(d/d)) mice developed to adulthood and showed normal ovarian function, but females were infertile with severely compromised uterine development and function characterized by cell cycle arrest, apoptosis, and altered adenogenesis (endometrial gland morphogenesis), resulting in failure of implantation and decidualization. By contrast, mice heterozygous for REA (REA(f/d)) had a very different phenotype, with estradiol treatment resulting in hyperstimulated, large uteri showing increased prol...Continue Reading

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Citations

Jan 8, 2013·Molecular Aspects of Medicine·Shuang ZhangD Randall Armant
Nov 8, 2014·PloS One·Katherine V Clark-KnowlesMichael W McBurney
Aug 21, 2014·Endocrine Reviews·Birgit Gellersen, Jan J Brosens
Jul 23, 2014·Molecular Endocrinology·Sandeep PawarMilan K Bagchi
Jul 24, 2012·Endocrinology·Fuller W Bazer
Nov 1, 2018·Reproductive Medicine and Biology·Takafumi NamikiNaomi Kashiwazaki

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