is a Progesterone Target Gene in the Endometrium of Ruminants.

Forkhead Box L2 (FOXL2) is a member of the FOXL class of transcription factors, which are essential for ovarian differentiation and function. In the endometrium, FOXL2 is also thought to be important in cattle; however, it is not clear how its expression is regulated. The maternal recognition of pregnancy signal in cattle, interferon-Tau, does not regulate expression. Therefore, in the present study, we examined whether the ovarian steroid hormones that orchestrate implantation regulate gene expression in ruminants. In sheep, we confirmed that mRNA and protein was expressed in the endometrium across the oestrous cycle (day 4 to day 15 post-). Similar to the bovine endometrium, ovine endometrial expression was low during the luteal phase of the oestrous cycle (4 to 12 days post-) and at implantation (15 days post-) while mRNA and protein expression significantly increased during the luteolytic phase (day 15 post- in cycle). In pregnant ewes, inhibition of progesterone production by trilostane during the day 5 to 16 period prevented the rise in progesterone concentrations and led to a significant increase of expression in caruncles compared with the control group (1.4-fold, < 0.05). Ovariectomized ewes or cows that were supplemented with exogenous progesterone for 12 days or 6 days, respectively, had lower endometrial expression compared with control ovariectomized females (sheep, mRNA, 1.8-fold; protein, 2.4-fold; cattle; mRNA, 2.2-fold; < 0.05). Exogenous oestradiol treatments for 12 days in sheep or 2 days in cattle did not affect endometrial expression compared with control ovariectomized females, except at the protein level in both endometrial areas in the sheep. Moreover, treating bovine endometrial explants with exogenous progesterone for 48h reduced expression. Using in vitro assays with COS7 cells we also demonstrated that progesterone regulates the promoter activity through the progesterone receptor. Collectively, our findings imply that endometrial is, as a direct target of progesterone, involved in early pregnancy and implantation.