The decline of pregnancy rate and abnormal uterine responsiveness of steroid hormones in aging mice.

Reproductive capacity in animals and women declines with increasing age. Although ovarian aging is considered as a main cause for the decline of pregnancy rate, whether uterine aging occurs remains unclear. Even if blastocysts are transferred from young donors to older pseudopregnant recipients, the rate of implantation is still low, suggesting the occurrence of uterine aging. In this study, we compared the pregnancy rate and the uterine responsiveness of steroid hormones in ovariectomized mice at age between 2- and 12-month-old. Compared to 2-month-old mice, there is a significant decrease of both pregnancy rate and the number of implantation sites in 12-month-old mice. In ovariectomized mice, the uterine responsiveness of steroid hormones is also significantly different between 2- and 12-month-old mice. On day 4, Muc1 and PR level in 12-month-old mice is significantly higher than that in 2-month-old mice, while Hand2 level is significantly lower in 12-month-old mice. Our data suggest that the abnormal responsiveness of steroid hormones may contribute to the decline of pregnancy rate in 12-month-old mice.

Progesterone induces the expression of lipocalin-2 through Akt-c-Myc pathway during mouse decidualization.

Lipocalin-2 (Lcn2) is a small glycoprotein involved in a number of biological processes such as inflammation and antibacterial response. In our study, Lcn2 is expressed in the subluminal stromal cells at implantation site on day 5 of pregnancy. The expression of Lcn2 in stromal cells is under the control of progesterone through Akt-c-Myc signaling pathway. Data from Lcn2 knockdown and recombinant protein treatments indicate that Lcn2 promotes mPGES-1 expression in stromal cells. The expression of Lcn2 and mPGES-1 is strongly stimulated by lipopolysaccharide (LPS), indicating that Lcn2 mediates LPS-induced inflammation. These findings shed light on the role of Lcn2 during decidualization.