title: Uterine glucocorticoid receptors are critical for fertility in mice through control of embryo implantation and decidualization.
abstract: In addition to the well-characterized role of the sex steroid receptors in fertility and reproduction, organs of the female reproductive tract are also regulated by the hypothalamic-pituitary-adrenal axis. These endocrine organs are sensitive to stress-mediated actions of glucocorticoids, and the mouse uterus contains high levels of the glucocorticoid receptor (GR). Although the presence of GR in the uterus is well established, uterine glucocorticoid signaling has been largely ignored in terms of its reproductive and/or immunomodulatory functions on fertility. To define the direct in vivo function of glucocorticoid signaling in adult uterine physiology, we generated a uterine-specific GR knockout (uterine GR KO) mouse using the PR(cre) mouse model. The uterine GR KO mice display a profound subfertile phenotype, including a significant delay to first litter and decreased pups per litter. Early defects in pregnancy are evident as reduced blastocyst implantation and subsequent defects in stromal cell decidualization, including decreased proliferation, aberrant apoptosis, and altered gene expression. The deficiency in uterine GR signaling resulted in an exaggerated inflammatory response to induced decidualization, including altered immune cell recruitment. These results demonstrate that GR is required to establish the necessary cellular context for maintaining normal uterine biology and fertility through the regulation of uterine-specific actions.
authors.affiliation: Signal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709;
authors.forename: Shannon D
authors.initials: SD
authors.lastname: Whirledge
authors.affiliation: Signal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709;
authors.forename: Robert H
authors.initials: RH
authors.lastname: Oakley
authors.affiliation: Comparative Medicine Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709;
authors.forename: Page H
authors.initials: PH
authors.lastname: Myers
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030.
authors.forename: John P
authors.initials: JP
authors.lastname: Lydon
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030.
authors.forename: Francesco
authors.initials: F
authors.lastname: DeMayo
authors.affiliation: Signal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709; cidlows1@niehs.nih.gov.
authors.forename: John A
authors.initials: JA
authors.lastname: Cidlowski
mesh_terms: D000818:Animals; D003656:Decidua / Q000502:physiology*; D010064:Embryo Implantation / Q000502:physiology*; D005260:Female; D005298:Fertility / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000502:physiology*; D014599:Uterus / Q000378:metabolism*
chemical_list: D011965:Receptors, Glucocorticoid
keywords: decidualization; glucocorticoid receptor; implantation; uterus