Variants of the EPPIN gene affect the risk of idiopathic male infertility in the Han-Chinese population

Ding, Xinliang; Zhang, Jie; Fei, Juan; Bian, Zenghui; Li, Yingchun; Xia, Yankai; Lu, Chuncheng; Lin, Song; Wang, Shoulin; Wang, Xinru

doi:10.1093/humrep/deq119

Cited by 21 publications

(9 citation statements)

References 14 publications

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“…In humans, the EPPIN gene is located on chromosome 20 in position 20q12–13.2 [ 40 ]. Genetic polymorphisms of EPPIN have recently been reported, some associated with infertility [ 41 ]. Although predominantly epididymal in expression, a more detailed transcriptomic study revealed that EPPIN is not strictly epididymis-specific since the testis (Sertoli cells) also expresses and secretes EPPIN which is thus found in small proportion on the surface of testicular spermatozoa.…”

Section: Proteins and Epididymal Activities In The Pipeline Of Potentmentioning

confidence: 99%

Epididymal approaches to male contraception

Drevet

2018

Basic Clin. Androl.

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Today, a vast arsenal of contraceptive methods interfering at different levels of the female reproductive axis is available. This is not the case for men for whom, until now, there is no reliable male reversible method and for whom vasectomy, condom and withdrawal are the only options available. Despite this limited supply, more than one third of all contraceptive methods used worldwide rely on the cooperation of the male partner. Besides developing hormonal approaches to stop sperm production, there may be attractive approaches that will interfere with sperm functions rather than production. Sperm functions are primarily established during post-testicular maturation, with the epididymis accounting for the majority. The purpose of this review is to present some of the promising and/or already abandoned leads that emerge from research efforts targeting the epididymis and its activities as potential means to achieve male post-meiotic contraception.

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Section: Proteins and Epididymal Activities In The Pipeline Of Potentmentioning

confidence: 99%

Epididymal approaches to male contraception

Drevet

2018

Basic Clin. Androl.

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“…An unusual mRNA splice variant of EPPIN isoform 1 has been reported in the human testis that has the addition of a WAP domain (exon 2) from the neighboring WAP6 gene (Clauss et al, 2002; GenBank NM_001198986); an actual protein from this variant has not been identified in human tissues. A number of single‐nucleotide polymorphisms of EPPIN have been reported (Ding et al, 2010), some of which may be associated with infertility.…”

Section: Epididymal Protease Inhibitormentioning

confidence: 99%

Epididymal Protein Targets: A Brief History of the Development of Epididymal Protease Inhibitor as a Contraceptive

O’Rand

Widgren

Hamil

et al. 2011

Journal of Andrology

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ABSTRACT:The Laboratories for Reproductive Biology at the University of North Carolina at Chapel Hill began collaboration with Human Genome Sciences (Rockville, Maryland) to sequence a human epididymal library and identify epididymal-specific genes. Among the first clones obtained from Human Genome Sciences was a clone for EPPIN (official symbol, SPINLW1). Our laboratory has described EPPIN (epididymal protease inhibitor) as a novel gene on human chromosome 20q12-13.2 that encodes a cysteinerich protein containing both Kunitz-type and WAP-type 4-disulfide core consensus sequences that characterize it as a protease inhibitor. EPPIN expresses 3 mRNA splice variants that encode 2 protein isoforms found in the testis and epididymis. Of the 2 isoforms, 1 is secreted and 1 lacks a secretory signal piece. EPPIN is predominantly a dimer, although multiples often exist, and in its native form, EPPIN is found on the sperm surface complexed with lactotransferrin and clusterin. During ejaculation, semenogelin from the seminal vesicles is bound to the EPPIN protein complex, initiating a series of events that define EPPIN's function: modulating prostate-specific antigen (PSA) activity, providing antimicrobial protection, and binding semenogelin, thereby inhibiting sperm motility. As PSA hydrolyzes semenogelin in the ejaculate coagulum, spermatozoa gain progressive motility. Using immunization as a tool to study antigen function, we demonstrated that EPPIN is essential for fertility because immunization of male monkeys with recombinant EPPIN results in complete, but reversible, contraception. To exploit our understanding of EPPIN's function, we have developed a high-throughput screen to look for compounds that inhibit EPPIN-semenogelin interaction and mimic anti-EPPIN, inhibiting sperm motility. These compounds are now being developed into a nonhormonal male contraceptive.

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“…The EPPIN protein provides a base to be able to reduce human sperm motility, preventing the spermatozoa from fertilizing the egg ( O’Rand et al, 2011 ; O’Rand et al, 2016 ; O’Rand et al, 2018 ). The variants to the gene has also been reported to associate with male infertility ( Ding et al, 2010 ). Moreover, The antibody to the EPPIN protein also raise a possibility as a contraceptive by inhibiting the action of the subsequent protein in the pathway of the spermatozoa to gain fertilization capability ( O’rand et al, 2004 ).…”

Section: Discussionmentioning

confidence: 99%

The Expressional Pattern of Epididymal Protease Inhibitor (EPPIN) in the Male Syrian Hamsters

et al. 2018

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The spermatogenesis is the process by which spermatozoa are generated in the testes. The spermatozoa travel male reproductive tract during which they meet many substances secreted from reproductive organs. One of the substances is epididymal protease inhibitor (EPPIN) that is involved in the post-testicular maturation including capability of fertilizing the eggs. The expression of EPPIN gene was investigated in various tissues of sexually mature and regressed male Syrian hamsters by reverse transcription polymerase chain reaction (RT-PCR). The EPPIN gene was identified in the testis and epididymis of the male Syrian hamsters and compared to the genes reported previously. There was no expression of EPPIN gene in reproductively and completely regressed testes of Syrian hamster. These results suggest that the expressions of the EPPIN gene are associated with the reproductive capability in the Syrian hamsters.

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Variants of the EPPIN gene affect the risk of idiopathic male infertility in the Han-Chinese population

Abstract: These results suggest that different variants in the EPPIN gene may have different relationships with idiopathic male infertility and men carrying these variants have a decreased or increased risk of abnormal semen parameters associated with male infertility.

Cited by 21 publications

References 14 publications

Epididymal approaches to male contraception

Epididymal approaches to male contraception

Epididymal Protein Targets: A Brief History of the Development of Epididymal Protease Inhibitor as a Contraceptive

The Expressional Pattern of Epididymal Protease Inhibitor (EPPIN) in the Male Syrian Hamsters

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