Background:
Recent studies have demonstrated that endometrial DNA
methylation is essential for embryo implantation during early pregnancy. Dnmt3a is one
of the key enzymes for DNA methylation and could be expressed in the endometrium
regularly at this stage.
Objective and Methods:
In this study, we conditionally ablated uterine Dnmt3a using
progesterone receptor-cre (Pgrcre) to define the physiological roles of Dnmt3a in female
reproduction.
Results:
We found that ovarian function was not apparently altered and the number of
embryo implantation sites in Dnmt3aloxP/loxP Pgrcre/+ (cKO) was not significantly varied
during early pregnancy. Western blotting and immunohistochemistry results showed no
difference in expression or location of the estrogen receptor α (ERα) and mucin 1
(Muc1), the marker of uterine receptivity. Although the expression of decidual markers,
matrix metalloproteinase-2 (Mmp2), matrix metalloproteinase-9(Mmp9), and bone
morphogenetic protein-2 (Bmp2), was slightly decreased in Dnmt3a cKO females, the
gross morphology of mice uteri during decidualization was not significantly influenced. In
the artificial induction of the decidualization model, there was also no remarkable
difference in visually observed morphology or uterine weight in Dnmt3a cKO. Lastly, a
continuous breeding study showed that the fertility of Dnmt3a cKO female mice was not
strikingly altered.
Conclusion:
Overall, these results demonstrated that although some decidual markers
are expressed abnormally, conditional knockout of Dnmt3a in the uterus did not
significantly affect the endometrial function during embryo implantation; the embryo
could implant into the endometrium normally.
Early Pregnancy Human Decidua is Enriched with Activated, Fully Differentiated and Pro-Inflammatory Gamma/Delta T Cells with Diverse TCR Repertoires