Epidermal Growth Factor,Transforming Growth Factor-α,and Epidermal Growth Factor Receptor Localization in the Baboon (Papio anubis) Uterus During the Menstrual Cycle and Early Pregnancy

Abstract

OBJECTIVE: Marked alterations occur in the synthesis of endometrium-specific proteins during the first third of pregnancy in the baboon. Because epidermal growth factor (EGF) expression has been associated with proliferation in the human and mouse endometrium, we hypothesized that EGF, transforming growth factor-α (TGFα), and EGF receptor (EGF-R) expression in baboon endometrium may be modulated by the early invasive trophoblast and play a role in decidualization of the endometrial stroma.

METHODS: Endometrial tissue was obtained from cycling baboons (n = 4-5 per time point), ovariectomized steroid-treated baboons (n = 4 per group), or from pregnant baboons on days 18-60 of pregnancy (n = 2-4 pergroup). The tissue was fixed in Bouin's solution and embedded in paraffin for immunocytochemistry using polyclonal antibodies against EGF and EGF-R and a monoclonal antibody to TGFα.

RESULTS: Endometrial staining was located almost entirely in the glandular epithelium for TGFα and EGF-R in the follicular phase animals, whereas EGF staining was strongest in the periglandular stroma. In the luteal phase, specific staining for EGF also was detected in the glands as well as the periglandular stroma. There appeared to be little difference in endometrial staining between the late follicular and mid-luteal phase for TGFα and EGF-R. A similar pattern was observed in the steroid-treated animals. In the endometrium from pregnant animals, EGF, TGFα, and EGF-R intensely stained the glandular epithelium on days 18, 25, and 32. Both EGF and EGF-R showed light stromal staining on days 18 and 25. Light stromal TGFα staining was present on day 25 and became moderately intense by day 32. By day 60, the most intense staining for EGF and EGF-R was stromal. Staining of TGFα continued to be strong in the remaining epithelium through day 60. In placenta, EGF and EGF-R intensely stained the syncytiotropho blast, but not the cytotrophoblast, whereas TGFα stained only the villous cytotrophoblast and intermediate cytotrophoblast within maternal blood vessels. There appeared to be no change in this staining pattern or intensity in the placenta throughout early pregnancy.

CONCLUSIONS: This study demonstrates the presence of EGF, TGFα, and EGF-R in the endometrium during the cycle and early pregnancy. The detection of EGF, TGFα, and EGF-R in the stromal cells during pregnancy correlated with the onset of decidualization. We propose that EGF, TGFα, and EGF-R may play a role in glandular development during the cycle and in decidualization and implantation during early pregnancy. (J Soc Gynecol Invest 1994 ;1 :277-84)