Background:
A well-known tissue marker of ovarian cancer, Human Epididymis protein
4 (HE4) is the member of whey acidic four-disulfide core proteins family. Purified from human
seminal plasma and characterized as a cross-class protease inhibitor, HE4 was proposed to shield
spermatozoa against proteolytic factors. However, its exact biological function is unknown. Proteins
usually function in conjunction with other proteins in the system and thus, identification and
analysis of protein networks become essential to decode protein functions.
Objective:
This study was performed to explore possible role(s) of HE4 in reproductive physiology
via identification of its interactome in human seminal plasma.
Methods:
HE4 binding proteins were identified through co-immunoprecipitation and MALDITOF/
MS analysis. Also, HE4 was quantified by ELISA in fertile and infertile human seminal
plasma samples.
Results:
Ten HE4 binding proteins were identified, viz. protein phosphatase 1 regulatory subunit
21, protein kinase CLK3, Ankyrin repeat domain-containing protein36A, prostatic acid phosphatase,
KIF5C, Spectrin repeat containing, nuclear envelope 1, isoform CRAf, tropomyosin 4, vezatin,
utrophin and fibronectin1. This interaction network suggests that HE4 plays multiple roles,
specifically in capacitation, sperm motility and maturation. Further, HE4 concentration in human
seminal plasma samples was determined by Elisa. Higher HE4 expression in normozoospermia
compared to azoospermia and asthenozoospermia affirms its importance in fertilization.
Conclusion:
Based on identified interactome, it is plausible that HE4 plays a crucial role in fertilization,
specifically in sperm maturation, motility and capacitation.
Allergy to Human Seminal Plasma
