Progesterone and Interferon Tau Regulate Hypoxia-inducible factors (HIFs) in the Endometrium of the Ovine Uterus. [Endocrinology] Journal article

In ruminants, progesterone (P4) from the ovary and interferon tau (IFNT) from the elongating blastocyst regulate expression of genes in the endometrium that are hypothesized to be important for uterine receptivity and blastocyst development. These studies determined effects of the estrous cycle, pregnancy, P4, and IFNT on HIF (hypoxia-inducible factor) expression in the ovine uterus. HIF1A mRNA, HIF2A mRNA and HIF2A protein were most abundant in the endometrial luminal (LE) and superficial glandular (sGE) epithelia of the uterus and conceptus trophectoderm. During the estrous cycle, HIF1A and HIF2A mRNA levels were low to undetectable on Day 10 in the endometrial LE/sGE, increased between Days 10 to 14, and then declined on Day 16. Both HIF1A and HIF2A mRNA were more abundant in the endometrial LE/sGE of pregnant ewes. However, HIF3A, HIF1B, HIF2B and HIF3B mRNA abundance was low in most cell types of the endometria and conceptus. Treatment of ovariectomized ewes with P4 induced HIF1A and HIF2A in the endometrial LE/sGE and intrauterine infusion of ovine IFNT further increased HIF2A in P4-treated ewes, but not in ewes treated with P4 and the anti-progestin ZK 136,317. HIF3A, HIF1B, HIF2B and HIF3B mRNA abundance was not regulated by either P4 or IFNT. Two HIF-responsive genes, CITED2 and VEGFA, were detected in both the endometrium and conceptus. These studies identified new P4-induced (HIF1A and HIF2A) and IFNT-stimulated (HIF2A) genes in the uterine LE/sGE and implicate the HIF pathway in regulation of endometrial epithelial functions and angiogenesis as well as peri-implantation blastocyst development.

Endocrinology