Peptides in Seminal Fluid and Their Role in Infertility: A Potential Role for Opiorphin Inhibition of Neutral Endopeptidase Activity as a Clinically Relevant Modulator of Sperm Motility: A Review

Abstract

Infertility is a devastating medical condition that adversely affects emotional health and well-being of couples who desire pregnancy and parenthood. The overall demographic data suggest that the indication for more than one-third of assisted reproductive technology cycles performed in the United States includes male factor infertility. There is increasing recognition of the role that peptides present in seminal plasma have in determining sperm motility. Several recent studies suggest that peptidases, such as neutral endopeptidase (NEP) and aminopeptidase N (APN), impose significant adverse effects on sperm motility. Interestingly, several recent studies demonstrate that there is an endogenous NEP/APN inhibitor peptide called opiorphin in human seminal plasma. Our pilot studies suggest opiorphin promotes sperm motility and may positively influence sperm motility parameters in some cases of males infertility characterized by asthenozoospermia.

Neprilysin expression and functions in development, ageing and disease

“…Apart from synthetic NEP inhibitors there are some natural endogenous NEP inhibitors, including the stress-response peptide, sialorphin ( Rougeot et al, 2003 ) and “opiorphins”, which possess strong analgesic properties ( Wisner et al, 2006 ). Some studies have also suggested that opiorphins promote sperm motility which adds another important role to the list of NEP functions and therapeutic avenues ( Bosler et al, 2014 ). Role of NEP in development and modulation of pain, stress response, addiction, sexuality, and food intake has recently been reviewed in ( Roques, 2018 ).…”

Concentrations of minerals in the canine prostatic fluid

“…Although it has been postulated that small amounts of prostatic fluid protect spermatozoa from capacitation and oxidative stress (Nöthling et al, , ), detailed effects on fertility are not well understood. Different to this, correlations between male fertility and the composition of seminal plasma are well established in human medicine (Bosler, Davies, & Neal‐Perry, ; Fallah, Mohammad‐Hasani, & Colagar, ). In contrast, information from the dog is sparse and data presented in the literature are based on small numbers of ejaculates/dogs only.…”

Elevated aminopeptidase N affects sperm motility and early embryo development

“…It has been reported that the seminal plasma proteins play a potential role in the regulation of male fertility [ 29 ]. However, the relationship between APN and sperm/male fertility reported by several investigators remains discordant [ 13 , 15 , 17 , 18 ]. In the present study, we supplemented APN in sperm culture medium during capacitation in order to understand the specific role of APN in the regulation of sperm function(s) and fertilization.…”

“…Consistent with the findings of Arienti et al ., localization of this enzyme has also been confirmed in human sperm membrane by another research group [ 15 ]. Although a number of observations made in the laboratory and during human clinical studies have suggested a possible role for altered APN levels in several diseases [ 16 , 17 ], the underlying role of this enzyme in regulating male fertility remains poorly understood.…”