title: Foxa2 is essential for mouse endometrial gland development and fertility.
abstract: During embryonic development, Foxa2 is required for the formation of the node and notochord, and ablation of this gene results in defects in gastrulation, neural tube patterning, and gut morphogenesis. Foxa2 has been shown to be expressed specifically in the glandular epithelium of the murine uterus. To study the uterine function of Foxa2, this gene was conditionally ablated in the mouse uterus by crossing mice with floxed Foxa2 alleles, Foxa2(loxP/loxP), with the Pgr(cre) mouse model. Pgr(cre/+) Foxa2(loxP/loxP) mice showed significantly reduced fertility. Analysis of the uterus on Day 5.5 of pregnancy showed disrupted blastocyst implantation. Pgr(cre/+) Foxa2(loxP/loxP) mice also showed a severe impairment of the uterus to respond to the artificial induction of the decidual response. Morphological examination of the uteri of these mice showed a severe reduction in the number of endometrial glands. The loss of endometrial glands resulted in the reduction of leukemia inhibitory factor (Lif) expression. The lack of a decidual response could be partially rescued by an intrauterine injection of LIF before the initiation of the decidual response. This analysis demonstrates that Foxa2 regulates endometrial gland development and that mice with a loss of endometrial glands cannot support implantation in part due to the loss of LIF, which is a requisite for fertility in the mouse.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Jeong
authors.forename: Inseok
authors.initials: I
authors.lastname: Kwak
authors.forename: Kevin Y
authors.initials: KY
authors.lastname: Lee
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Kim
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Large
authors.forename: Colin L
authors.initials: CL
authors.lastname: Stewart
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Kaestner
authors.forename: John P
authors.initials: JP
authors.lastname: Lydon
authors.forename: Francesco J
authors.initials: FJ
authors.lastname: DeMayo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D010064:Embryo Implantation / Q000187:drug effects / Q000502:physiology*; D004717:Endometrium / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D051542:Hepatocyte Nuclear Factor 3-beta / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D010929:Placentation / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D011555:Pseudopregnancy / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C496503:Foxa2 protein, mouse; D051542:Hepatocyte Nuclear Factor 3-beta; D011374:Progesterone; D004958:Estradiol