Detection of transforming growth factor-α and epidermal growth factor receptor mRNA and immunohistochemical localization of their proteins in the ovine uterus during the early implantation period

Accumulated evidence suggests that growth factors of the epidermal growth factor (EGF) family play an important role in the murine implantation process. In the sheep, however, the uterine distribution of these factors and their receptor, EGF receptor (EGF-R), during implantation is not known. This study examined the presence of mRNA transcripts and immunohistochemical localization for transforming growth factor-alpha (TGF-alpha), the potent EGF-family member, and EGF-R in the ovine uterus during the early implantation period. By reverse transcriptase-polymerase chain reaction and sequencing of the products, the presence of TGF-alpha and EGF-R mRNA transcripts were detected in the endometrium on Days 14, 16 and 20 (Day 0=day of mating). Immunohistochemical analysis revealed that the luminal and glandular epithelial cells and some stromal cells of the endometrium and the trophectoderm were positive for TGF-alpha and EGF-R on Days 14 and 15. Distinct staining for TGF-alpha was observed in the glandular epithelium of deep endometrial areas and strong immunoreactivity for EGF-R was found in the trophectoderm. On Days 16, 18 and 20, although the staining pattern for TGF-alpha was similar to that on the previous days, the immunoreactivity for EGF-R in the stromal cells increased and that in the gland decreased. A distinct immunoreactivity for EGF-R was found in the trophectoderm throughout the days examined. These results suggest that TGF-alpha expressed in the endometrium and trophectoderm may exert effects locally on these tissues during implantation in sheep. Furthermore, it is speculated that the temporal changes in the uterine EGF-R distribution may be related to the endometrial microvascular development.