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Vasectomy-Dependent Dysregulation of a Local Renin-Angiotensin System in the Epididymis of the Cynomolgus Monkey (Macaca fascicularis)

From the Centre de Recherche en Biologie de la Reproduction et Département d'Obstétrique-Gynécologie, Faculté de Médecine, Université Laval, Québec, Canada. ^* Present address: Laboratoire "Epididyme et maturation des gamètes," Université Blaise Pascal, CNRS UMR 6547 GEEM, 24 avenue des Landais, 63177 Aubière Cedex, France.

Correspondence to: Robert Sullivan, Unité d'Ontogénie-Reproduction, Centre de Recherche, Centre Hospitalier de l'Université Laval, 2705 Blvd Laurier, Ste-Foy, PQ, Canada, G1V 4G2 (e-mail: robert.sullivan{at}crchul.ulaval.ca).

The mammalian epididymis is a fundamental organ for sperm cell maturation; it allows mammals to acquire their fertilizing ability. We have previously shown that during obstruction in cases of vasectomy, gene expression profiles were modified in human and cynomolgus monkey epididymides. Paracrine factors thus appear to be key elements in local gene expression along the epididymis. Local renin-angiotensin systems (RAS) have been described in many other organs as paracrine regulators of gene expression. This work demonstrates the presence of a local RAS in the epididymis of the cynomolgus monkey and investigates the vasectomy-dependent changes occurring in this system. After unilateral vasectomy in 4 monkeys (two for 3 days and two others for 7 days), the presence of two major components of the RAS (ie, angiotensinogen [ANG] and the type 1 receptor to angiotensin II [AT-I]) was evaluated in the vasectomized and the normal controlateral epididymides of each monkey. We also show by in situ hybridization that the principal cells of the epididymis express ANG and AT-I mRNAs and immunohistochemistry permitted to verify the co-localization of the AT-I protein and mRNA. Quantitative comparisons of individual variations in the mRNA and protein profiles for ANG and AT-I revealed that vasectomy altered the RAS expression profiles in an individual manner, thus confirming its role as a local system. This study provides a good basis for further investigation of the possible implications of the RAS in the physiology of the epididymis. Furthermore, the individual dependent modifications are in accordance with the very fluctuating results obtained in the fertility status of human patients undergoing a vasectomy reversal. The variations observed in the RAS expression profiles may be a good model to study the causes of the overall epididymal gene expression dysregulation that follows vasectomy and potentially affects fertility.

     Key words: Excurrent duct, sperm maturation, angiotensinogen, type 1 receptor to angiotensin II