(Pro)renin Receptor Is Present in Human Sperm and It Adversely Affects Sperm Fertility Ability

Abstract

Sperm fertility ability may be modulated by different molecular systems, such as the renin-angiotensin system (RAS). Although renin is one of its most relevant peptides, the presence and role of the (pro)renin receptor (PRR) is completely unknown. We have proved for the first time the existence of PRR and its transcript in human sperm by western blot and RT-PCR. Immunofluorescence studies showed that this receptor is mainly located in the apical region over the acrosome and in the postacrosomal region of the sperm head and along the sperm tail. In addition, this prospective cohort study also proves that semen samples with higher percentages of PRR-positive spermatozoa are associated with poor sperm motility, worse blastocyst development and no-viable blastocysts. Our results provide insight into how PRR play a negative role in sperm physiology that it may condition human embryo quality and development. An in-depth understanding of the role of PRR in sperm fertility can help elucidate its role in male infertility, as well as establish biomarkers for the diagnosis or selection of sperm to use during assisted reproductive techniques.

Epithelial and Neural Cadherin in Mammalian Fertilization: Studies in the Mouse Model

“…Participation of the sperm post-acrosomal region in binding/fusion to the oolemma has been proposed in studies done in several species [ 49 , 50 , 51 ]. In particular, previous reports have described post-acrosomal localization of several sperm proteins highly relevant to fertilization, among them FA-1, CD9 and CD91 osteopontin, ERp29, PLCζ, and PR-R (ProRenin receptor) [ 52 , 53 , 54 , 55 , 56 , 57 ]. Specifically, FA-1 was proposed to mediate primary sperm-ZP binding in humans and mouse models [ 52 ], while CD9 and CD81 are members of the tetraspanin superfamily and were found to participate in sperm–egg membrane fusion [ 53 ].…”

“…On the other hand, osteopontin was defined as a fertility marker in bull spermatozoa [ 54 ], and ERp29 has been associated to gamete interaction, by triggering sperm binding to egg receptors [ 55 ]. Finally, PLCz, has been involved in egg activation [ 56 ], and higher percentages of PRR-positive spermatozoa were associated with poor sperm motility, and worse blastocyst development [ 57 ]. Specifically regarding mechanisms of cell signalling in spermatozoa, Epac1 and 2 proteins were found in spermatozoa, localized in the post-acrosomal region, related to sperm motility, capacitation and AE and associated to E-cad redistribution when activated [ 58 ].…”