Identification and characterization of RSIY-11, a novel seminal peptide derived from semenogelin-1, which acts as a neutral endopeptidase inhibitor modulating sperm motility

Purpose Based on prior reports demonstrating that neutral endopeptidase (NEP) inhibitors increase sperm motility, the goal of our studies was to identify endogenous seminal peptides that inhibit NEP and investigate their potential effect on sperm motility. Methods Peptidomic analysis was performed o...

Full description

Saved in:
Bibliographic Details
Published in:Journal of assisted reproduction and genetics 2019-09, Vol.36 (9), p.1891-1900
Main Authors: Fritz, Rani, Mukherjee, Amarnath, Zaghi, Sahar, Agalliu, Ilir, Jindal, Sangita, Tashima, Alexandre K., Fricker, Lloyd D., Davies, Kelvin P.
Format: Article
Language:English
Subjects:
Adult
Dose-Response Relationship, Drug
Endopeptidase
Fertility
Gamete Biology
Gynecology
Human Genetics
Humans
Infertility
Infertility, Male
Male
Medicine
Medicine & Public Health
Motility
Neprilysin
Neprilysin - antagonists & inhibitors
Neprilysin - metabolism
Oligopeptides - pharmacology
Patients
Peptide Fragments - administration & dosage
Peptide Fragments - chemistry
Peptide Fragments - pharmacology
Peptides
Reproductive Medicine
Salivary Proteins and Peptides - pharmacology
Semen - chemistry
Semen - metabolism
Seminal fluid
Seminal Vesicle Secretory Proteins - chemistry
Seminal Vesicle Secretory Proteins - metabolism
Sperm
Sperm Motility - drug effects
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Purpose Based on prior reports demonstrating that neutral endopeptidase (NEP) inhibitors increase sperm motility, the goal of our studies was to identify endogenous seminal peptides that inhibit NEP and investigate their potential effect on sperm motility. Methods Peptidomic analysis was performed on human seminal fluid, identifying 22 novel peptides. One peptide, named RSIY-11, derived from semenogelin-1, was predicted through sequence analysis to be a substrate and/or potential inhibitor of NEP. Enzymatic analysis was conducted to determine the inhibitory constant (Ki) of RSIY-11 as an inhibitor of NEP. Total and progressive sperm motility was determined at baseline and 30 and 60 min following addition of RSIY-11 to seminal fluid in 59 patients undergoing an infertility workup at an urban medical center. Additionally, the effects of RSIY-11 on sperm motility were evaluated in 15 of the 59 patients that met criteria for asthenospermia. Results RSIY-11 was shown to act as a competitive inhibitor of NEP with a Ki of 18.4 ± 1.6 μM. Addition of RSIY-11 at concentrations of 0.75 μM, 7.5 μM, and 75 μM significantly increased sperm motility at all time points investigated, with increases of 6.1%, 6.9%, and 9.2% at 60 min, respectively. Additionally, within the subgroup of patients with asthenospermia, RSIY-11 at concentrations of 0.75 μM, 7.5 μM, and 75 μM significantly increased sperm motility at all time points investigated, with increases of 7.6%, 8.8%, and 10.6% at 60 min, respectively. Conclusions RSIY-11 is a newly identified semenogelin-1-derived peptide present in seminal fluid. RSIY-11 acts as a potent competitive inhibitor of NEP, which when added to seminal fluid significantly increases sperm motility. RSIY-11 could play a potential role in the treatment for male factor infertility related to asthenospermia and improve intrauterine insemination outcomes.
ISSN:1058-0468
1573-7330
DOI:10.1007/s10815-019-01524-8