MENSTRUAL STAGE-SPECIFIC EXPRESSION OF EPIDERMAL GROWTH-FACTOR AND TRANSFORMING GROWTH-FACTOR-ALPHA IN HUMAN OVIDUCT EPITHELIUM AND THEIR ROLE IN EARLY EMBRYOGENESIS

We studied the expression of epidermal growth factor (EGF) and transfo rming growth factor (TGF)-alpha in human oviduct epithelium at various menstrual stages. Immunohistochemical stainings using anti-EGF and an ti-TGFalpha antibodies showed a specific staining in ampullary oviduct epithelium at late follicular and luteal stages, but the stainings we re very weak at early follicular stage. Quantitative reverse transcrip tion and polymerase chain reaction, using beta-actin messenger RNA as an internal standard, revealed the menstrual stage-specific expression of EGF and TGFalpha gene transcripts: relative amounts of EGF and TGF alpha messenger RNA to those of beta-actin were 1.5 +/- 1.9% (mean +/- SD) and 1.4 +/- 0.6% (n = 3) at early follicular, 16.5 +/- 4.9% and 1 2.6 +/- 2.6% (n = 3) at late follicular, and 18.9 +/- 2.2% and 13.8 +/ - 3.2% (n = 3) at luteal stages, respectively. The expression of these growth factors was in proportion to the increase in serum estradiol b ut not to progesterone levels. To clarify the biological significance of these growth factors, mouse two-cell embryos were cocultured with h uman oviduct epithelial cells with or without blocking the action of t hese growth factors. Cocultures significantly promoted blastocyst form ation, but this promotive effect of the oviduct epithelial cells was c ompletely abolished by the addition of anti-EGF and/or anti-TGFalpha m onoclonal neutralizing antibodies to the coculture system. All these r esults showed that EGF and TGFalpha were synthesized and expressed in human oviduct epithelium specifically to menstrual stages, and that th ese growth factors may be involved in early embryonic development.