Forkhead box a2 (FOXA2) is essential for uterine function and fertility.
Andrew M Kelleher1, Wang Peng1, James K Pru2
1Division of Animal Sciences, University of Missouri, Columbia, MO 65211.
Summary
The transcription factor FOXA2 is crucial for uterine gland development and fertility. Its absence causes infertility due to implantation defects, but LIF can rescue this, highlighting glands' role in early pregnancy.
Area of Science:
- Reproductive Biology
- Developmental Biology
- Genetics
Background:
- Embryo implantation and uterine decidualization are critical for pregnancy establishment.
- Uterine glands are essential for successful pregnancy in mice and likely humans.
- Forkhead box a2 (FOXA2) is a key regulator of uterine gland differentiation.
Purpose of the Study:
- To investigate the role of FOXA2 in adult uterine function and fertility.
- To determine the impact of FOXA2 deletion on uterine glands, embryo implantation, and decidualization.
- To explore the potential rescue effects of leukemia inhibitory factor (LIF).
Main Methods:
- Conditional deletion of FOXA2 in adult (Ltf-Cre) and neonatal (Pgr-Cre) mouse uteri.
- Morphological and histological analysis of uteri from FOXA2-deleted mice.
- Assessment of blastocyst implantation, stromal decidualization, and pregnancy outcomes.
- Administration of LIF to rescue implantation and pregnancy defects.
Main Results:
- Neonatal FOXA2 deletion resulted in completely aglandular uteri.
- Adult FOXA2-deleted mice were infertile with defective blastocyst implantation and decidualization.
- LIF expression was absent in early pregnancy in adult FOXA2-deleted mice.
- LIF administration rescued blastocyst implantation in both gland-containing and aglandular uteri.
- LIF rescued pregnancy to term in gland-containing mice but not in aglandular mice.
Conclusions:
- FOXA2 plays a critical, previously unrecognized role in adult uterine function and fertility.
- Uterine glands and their secretions are vital for blastocyst implantation and stromal decidualization.
- LIF can initiate implantation but is insufficient to maintain pregnancy without functional uterine glands.
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