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Original Studies |
Population Council and The Rockefeller University, New York, New York 10021; the Department of Obstetrics and Gynecology, Nassau County Medical Center, (S.K., A.D., Y.-K.Y.), New York, New York 11554; the Department of Obstetrics and Gynecology, Center for Reproductive Biology, University of Edinburgh (S.T.C., D.T.B.), Edinburgh, United Kingdom; and the Department of Obstetrics and Gynecology, New York University Medical School (F.S.), New York, New York 10016
Address all correspondence and requests for reprints to: Dr. Indrani C. Bagchi, The Population Council, 1230 York Avenue, New York, New York 10021. E-mail: indrani{at}popcbr.rockefeller.edu
The human endometrium acquires the ability to implant the developing embryo within a specific time window that is thought to open between days 1924 of the secretory phase of the menstrual cycle. During this period the endometrium undergoes pronounced structural and functional changes induced by the ovarian steroids, estrogen and progesterone, that prepare it to be receptive to invasion by the embryo. The identification of reliable biochemical markers to assess this critical receptive phase in the context of the natural cycle remains one of the major challenges in the study of human reproduction. Our previous studies in a rat model system demonstrated that the expression of calcitonin, a peptide hormone involved in calcium homeostasis, is transiently induced by progesterone in the glandular epithelium at the onset of implantation. Attenuation of calcitonin synthesis in the uterus during the preimplantation phase by administration of calcitonin antisense oligodeoxynucleotides severely impairs implantation of rat embryos, suggesting that this peptide hormone plays a critical role in uterine receptivity. To investigate whether calcitonin is also expressed in the human endometrium during implantation, we monitored the spatio-temporal expression of calcitonin on various days of the menstrual cycle. Our studies employing RT-PCR showed that calcitonin messenger ribonucleic acid is expressed in human endometrium during the postovulatory midsecretory phase (days 1725) of the menstrual cycle, with maximal expression occurring between days 1921. Very little calcitonin expression was detected in the endometrium in either the preovulatory proliferative (days 514) or the late secretory (days 2628) phase. In situ hybridization and immunocytochemical analyses localized the calcitonin expression predominantly in the glandular epithelial cells of the endometrium. Our studies further showed that calcitonin expression in the human endometrium is under progesterone regulation. Treatment of women with an antiprogestin, mifepristone (RU-486), drastically reduced calcitonin expression in the endometrium. Collectively, these findings reveal that progesterone-induced expression of calcitonin in the secretory endometrium temporally coincides with the putative window of implantation in the human.
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