Sexually dimorphic effects of forkhead box a2 (FOXA2) and uterine glands on decidualization and fetoplacental development
| Autor: | Susanta K. Behura, Andrew M. Kelleher, Pramod Dhakal, Thomas E. Spencer |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine endocrine system Placenta Uterus Biology Andrology Mice 03 medical and health sciences Fetus 0302 clinical medicine Pregnancy Decidua medicine Animals reproductive and urinary physiology Mice Knockout Sex Characteristics 030219 obstetrics & reproductive medicine Multidisciplinary Decidualization Biological Sciences respiratory system 030104 developmental biology medicine.anatomical_structure embryonic structures Hepatocyte Nuclear Factor 3-beta Female Metrial Gland Uterine gland Transcriptome Leukemia inhibitory factor |
| Zdroj: | Proc Natl Acad Sci U S A |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Glands of the uterus are essential for pregnancy establishment. Forkhead box A2 (FOXA2) is expressed specifically in the glands of the uterus and a critical regulator of glandular epithelium (GE) differentiation, development, and function. Mice with a conditional deletion of FOXA2 in the adult uterus, created using the lactotransferrin iCre (Ltf-iCre) model, have a morphologically normal uterus with glands, but lack FOXA2-dependent GE-expressed genes, such as leukemia inhibitory factor (LIF). Adult FOXA2 conditional knockout (cKO; Ltf(iCre/+)Foxa2(f/f)) mice are infertile due to defective embryo implantation arising from a lack of LIF, a critical implantation factor of uterine gland origin. However, intraperitoneal injections of LIF can initiate embryo implantation in the uterus of adult FOXA2 cKO mice with pregnancies maintained to term. Here, we tested the hypothesis that FOXA2-regulated genes in the uterine glands impact development of the decidua, placenta, and fetus. On gestational day 8.5, the antimesometrial and mesometrial decidua transcriptome was noticeably altered in LIF-replaced FOXA2 cKO mice. Viable fetuses were reduced in FOXA2 cKO mice on gestational days 12.5 and 17.5. Sex-dependent differences in fetal weight, placenta histoarchitecture, and the placenta and metrial gland transcriptome were observed between control and FOXA2 cKO mice. The transcriptome of the placenta with a female fetus was considerably more altered than the placenta with a male fetus in FOXA2 cKO dams. These studies reveal previously unrecognized sexually dimorphic effects of FOXA2 and uterine glands on fetoplacental development with potential impacts on offspring health into adulthood. |
| Databáze: | OpenAIRE |
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