Data from: Forkhead box a2 (FOXA2) impacts uterine decidualization and fetoplacental development

Glands of the uterus are essential for the establishment of pregnancy in
mice and likely humans. Forkhead box a2 (FOXA2) is a transcription factor
expressed specifically in the glands of the uterus and a critical
regulator of uterine gland 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 a considerable number of FOXA2-dependent
GE-expressed genes. Adult FOXA2 conditional knockout (cKO; Ltf-iCre:Foxa2
flox) mice are infertile due to defective embryo implantation arising from
a lack of leukemia inhibitory factor (LIF), a critical implantation factor
of uterine gland origin. 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 using a littermate study design. On gestational day (GD) 8.5,
the anti-mesometrial and mesometrial decidua transcriptome was noticeably
altered in FOXA2 cKO mice. Viable fetuses were reduced in FOXA2 cKO mice
on GDs 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 a
previously unrecognized biological role for FOXA2 and uterine glands on
fetoplacental development that exhibits sexual dimorphism. Thus, uterine
glands and, by inference, their products program fetoplacental development
with potential sexually dimorphic impacts on offspring health into
adulthood.