Ovine endometrial expression of transforming growth factor beta isoforms during the peri-implantation period

During the estrous cycle and early pregnancy, the uterus undergoes a variety of morphological changes. Because of their powerful effects on angiogenesis, on extracellular matrix modification, and on cellular proliferation and differentiation, the transforming growth factor beta (TGF beta) family of polypeptides may be involved in the regulation of pregnancy-related endometrial modification. In this study, endometrial steady-state mRNA expression of the three isoforms, TGF beta 1, beta 2, and beta 3, was quantified, and the proteins were localized during the later part of the estrous cycle (Days 13 and 16) and during early pregnancy (Days 13 through 30) in sheep, TGF beta 1 mRNA was expressed as a single transcript with steady-state mRNA expression levels 2-fold higher on Day 16 of the estrous cycle than on Day 13 of the estrous cycle (p less than or equal to 0.002) or Days 13 and 16 (p less than or equal to 0.004 and 0.008, respectively) of gestation. During pregnancy, levels increased progressively to peak on Day 27 (2.5-fold above Day 16 of pregnancy; p less than or equal to 0.0001) and then leveled off at Day 30. Immunocytochemical localization of TGF beta 1 demonstrated protein in glandular and luminal epithelium at all days examined. TGF beta 2 mRNA was expressed as five distinct transcripts, and mRNA expression levels were lowest in Day 16 pregnant endometrium. Thereafter the expression level increased steadily through Day 30 (p less than or equal to 0.0003). TGF beta 2 protein was localized in epithelium, diffusely within the endometrial stroma, and in leukocyte-like cells within the stroma, TGF beta 3 was expressed as one major transcript and two minor transcripts. As with TGF beta 1, there was a dramatic difference in TGF beta 3 levels between Day 16 of pregnancy and Day 16 of the estrous cycle (3.8-fold, p less than or equal to 0.0001), In pregnant ewes, endometrial TGF beta 3 levels increased 1.9-fold (p = 0.13) between Days 16 and 23 and remained relatively constant through Day 30. Immunohistochemistry localized TGF beta 3 protein most prominantly in the subepithelial stroma of the caruncule from Day 16 of the cycle in endometrial tissue. The observed changes in mRNA and protein expression patterns of TGF beta s within the ovine endometrium suggest that TGF beta s play a role in restructuring and modifying endometrium for a subsequent estrous cycle and/or pregnancy.