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Induction of Differentiated Trophoblast Function by Epidermal Growth Factor: Relation of Immunohistochemically Detected Cellular Epidermal Growth Factor Receptor Levels^*

Department of Obstetrics and Gynecology, Kobe University School of Medicine Kobe, Japan

Address requests for reprints to: Dr. Takeshi Maruo, Department of Obstetrics and Gynecology, Kobe University School of Medicine, 5–1 Kusunoki-cho 7-Chome, Chuo-ku, Kobe 650, Japan.

The effects of epidermal growth factor (EGF) on the production and secretion of hCG and human placental lactogen (hPL) by cultured placental tissues were investigated in relation to immunohistochemical measurements of cellular EGF receptor levels in the placenta.

Explants of trophoblastic tissues obtained from normal early and term placentas were cultured in the presence or absence of EGF (100 ng/mL) with or without processing inhibitors (baci-tracin, 1 mg/mL; colchicine, 100 µM; chloroquine, 100 µM) for 5 days, with EGF present for the first 2 days. Addition of EGF to the medium increased the release of hCG, hCG, and hPL by the cultured early placental tissues. This EGF-stimulated hCG, hCG, and hPL release was markedly inhibited by concomitant treatment with processing inhibitors. The time course of EGF effects indicated that the EGF-stimulated increase in hCG secretion required a lag period of approximately 1 day, whereas significant increases in hCG and hPL secretion became apparent only after 3 days of EGF treatment. By contrast, in term placental tissues EGF stimulated only hCGa and hPL release, with a lag period of approximately 3 days.

A possible direct action of EGF on the cultured placental tissues was reinforced by the immunohistochemical demonstration of EGF receptors in the placenta. When determined using the avidin/biotin immunoperoxidase method with monoclonal antibody to the mouse EGF receptor, EGF receptors were found predominantly on the syncytiotrophoblasts. Immunohistochem-ical measurements of cellular EGF receptor levels in the syncy-tiotrophoblasts revealed remarkably higher levels in early placenta compared to those in midterm and term placentas. Since EGF is likely to interact with its receptor, the lesser biological effects of EGF in cultures of term placental tissues may be due to the lower cellular EGF receptor levels in term placenta.

These results demonstrate that EGF, via its receptors on the syncytiotrophoblasts, stimulates the release of both hCG and hPL in normal early placenta. They also suggest that EGF may play a significant role in the induction and regulation of the differentiated function of trophoblasts.

^* This work was supported in part by Grants in Aid for Scientific Research 60570776 and 60480368 from the Japanese Ministry of Education Science and Culture.

Received July 1, 1986.

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