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Department of Biomedical Sciences and Technologies (S.C., G.R.), Faculty of Medicine, University of L’Aquila, 67100 L’Aquila, Italy; Department of Histology and Medical Embryology (M.B., R.C.), Faculty of Medicine, University of Rome "La Sapienza," 00161 Rome, Italy; and Department of Public Health and Cell Biology (L.S.), Histology Section, University of Rome "Tor Vergata," 00173 Rome, Italy
Address all correspondence and requests for reprints to: Rita Canipari, Department of Histology and Medical Embryology, University of Rome "La Sapienza," Via A. Scarpa 14, 00161 Rome, Italy. E-mail: rita.canipari{at}uniroma1.it.
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a bioactive peptide isolated from ovine hypothalamus. It is transiently expressed in preovulatory follicles and positively affects several parameters correlated with the ovulatory process. It has also been shown to be expressed in the interstitial tissue around primordial and preantral follicles. The aim of the present study was to investigate whether PACAP influences preantral follicle growth and differentiation. Mouse preantral follicles were cultured for 5 d in the presence of FSH and increasing concentrations of PACAP or vasoactive intestinal polypeptide (VIP) (10-12 to 10-7 M). In the presence of FSH, follicles increased in diameter and formed an antrum. At the concentrations tested, neither PACAP alone nor VIP alone had any effect on follicle development, but the addition of either peptide to FSH-stimulated follicles caused a dose-dependent inhibition of follicle growth, antrum formation, granulosa cell proliferation, and estradiol production. The effect of PACAP on follicle growth and antrum formation was directly correlated with the length of stimulation and was reversible. Although exposure of follicles to 10-7 M PACAP and VIP did not affect oocyte growth, it severely impaired completion of meiotic maturation in oocytes isolated from the follicles and cultured for 17 h in medium alone. The cyclic production of PACAP by preovulatory follicles during the estrous cycle in adult rats and its induction by LH in the rat and mouse ovary suggest that this peptide may play a role in the local regulation of preantral follicle growth.
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