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

Reprod Sci. 2014 Nov;21(11):1334-40. doi: 10.1177/1933719114536473. Epub 2014 May 22.


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.

Keywords: male infertility; seminal peptides; sperm motility.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Fertility
  • Humans
  • Infertility, Male / metabolism*
  • Infertility, Male / physiopathology
  • Male
  • Neprilysin / antagonists & inhibitors*
  • Neprilysin / metabolism
  • Oligopeptides / metabolism*
  • Proteinase Inhibitory Proteins, Secretory / metabolism*
  • Salivary Proteins and Peptides / metabolism*
  • Semen / metabolism*
  • Seminal Plasma Proteins / metabolism*
  • Signal Transduction
  • Sperm Motility*
  • Spermatozoa / enzymology*


  • Oligopeptides
  • Proteinase Inhibitory Proteins, Secretory
  • Salivary Proteins and Peptides
  • Seminal Plasma Proteins
  • glutaminyl-arginyl-phenylalanyl-seryl-arginine
  • Neprilysin