Epididymal P34H protein deficiency in men evaluated for infertility

Moskovtsev, Sergey I.; Jarvi, Keith; Légaré, Christine; Sullivan, Robert; Mullen, J. Brendan

doi:10.1016/j.fertnstert.2006.12.053

Cited by 32 publications

(18 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sylvester et al [26] have demonstrated that the level of rat epididymal CLU that is secreted only in the caput is ;7-fold higher in the epididymal fluid from the caput compared with that in the cauda. This is consistent with the fact that in the caput SPAM1 and other GPI-linked proteins are removed from the sperm plasma membrane [1,27], while in the caudal epididymis they are added to the sperm [25,28]. In the case of the prion protein and other GPI-linked proteins associated with the soluble phase, addition to the sperm surface occurs before [11] or after [25] ejaculation from the seminal plasma, where the level of CLU would be lower than that in the caput and cauda.…”

Section: Discussionsupporting

confidence: 86%

Clusterin Facilitates Exchange of Glycosyl Phosphatidylinositol-Linked SPAM1 Between Reproductive Luminal Fluids and Mouse and Human Sperm Membranes1

Griffiths

Galileo

Aravindan

et al. 2009

Biology of Reproduction

View full text Add to dashboard Cite

Glycosyl phosphatidylinositol (GPI)-linked proteins, which are involved in post-testicular maturation of sperm and have a role in fertilization, are acquired on the sperm surface from both vesicular and membrane-free soluble fractions of epididymal luminal fluid (LF) and uterine LF. Herein, we investigate the mechanism of uptake of these proteins from the soluble fraction of LFs using sperm adhesion molecule 1 (SPAM1) as a model. Ultracentrifugation and native Western blot analysis of the soluble fraction revealed that SPAM1 is present in low-molecular-weight (monomeric) and high-molecular-weight (oligomeric) complexes. The latter are incapable of transferring SPAM1 and may serve to produce monomers. Monomers are stabilized by hydrophobic interactions with clusterin (CLU), a lipid carrier that is abundantly expressed in LFs. We show that CLU is involved in the transfer of SPAM1 monomers, whose delivery was decreased by anti-CLU antibody under normal and apolipoprotein-enhanced conditions. Coimmunoprecipitation revealed an intimate association of CLU with SPAM1. Both plasma and recombinant CLU had a dose-related effect on transfer efficiency: high concentrations reduced and low concentrations enhanced delivery of SPAM1 to human and mouse sperm membranes, reflecting physiological states in the epididymal tract. We propose a lipid exchange model (akin to the lipid-poor model for cholesterol efflux) for the delivery of GPI-linked proteins to sperm membranes via CLU. Our investigation defines specific conditions for membrane-free GPI-linked protein transfer in vitro and could lead to technology for improving fertility or treating sperm pathology by the addition of relevant GPI-linked proteins critical for successful fertilization in humans and domestic animals.

show abstract

Section: Discussionsupporting

confidence: 86%

Clusterin Facilitates Exchange of Glycosyl Phosphatidylinositol-Linked SPAM1 Between Reproductive Luminal Fluids and Mouse and Human Sperm Membranes1

Griffiths

Galileo

Aravindan

et al. 2009

Biology of Reproduction

View full text Add to dashboard Cite

show abstract

“…This is supported by the results indicating that immunization against P34H inhibits sperm-zona binding in vitro (Boué et al 1994). Furthermore, the loss of P34H from sperm surface has been associated with idiopathic infertility in men (Boué & Sullivan 1996, Moskovtsev et al 2007, and human spermatozoa lacking P34H have been shown to be unable to bind to the extracellular matrix of oocyte (Boué & Sullivan 1996). However, the usefulness of P34H as a contraceptive target should be critically considered owing to the wide tissue distribution (Felsted & Bachur 1980) of its expression and the general metabolic role of carbonyl reductases in converting various carbonyl compounds to corresponding alcohols (Wermuth 1981).…”

Section: Carbonyl Reductasementioning

confidence: 65%

Novel epididymal proteins as targets for the development of post-testicular male contraception

Sipilä

Jalkanen²,

Huhtaniemi³

et al. 2009

Reproduction

View full text Add to dashboard Cite

Apart from condoms and vasectomy, modern contraceptive methods for men are still not available. Besides hormonal approaches to stop testicular sperm production, the post-meiotic blockage of epididymal sperm maturation carries lots of promise. Microarray and proteomics techniques and libraries of expressed sequence tags, in combination with digital differential display tools and publicly available gene expression databases, are being currently used to identify and characterize novel epididymal proteins as putative targets for male contraception. The data reported indicate that these technologies provide complementary information for the identification of novel highly expressed genes in the epididymis. Deleting the gene of interest by targeted ablation technology in mice or using immunization against the cognate protein are the two preferred methods to functionally validate the function of novel genes in vivo. In this review, we summarize the current knowledge of several epididymal proteins shown either in vivo or in vitro to be involved in the epididymal sperm maturation. These proteins include CRISP1, SPAG11e, DEFB126, carbonyl reductase P34H, CD52, and GPR64. In addition, we introduce novel proteinases and protease inhibitor gene families with potentially important roles in regulating the sperm maturation process. Furthermore, potential contraceptive strategies as well as delivery methods will be discussed. Despite the progress made in recent years, further studies are needed to reveal further details in the epididymal sperm maturation process and the factors involved, in order to facilitate the development of new epididymal contraceptives.

show abstract

“…This is the case of P25b, involved in the sperm maturation, since it is a protein acquired by the spermatozoa in the epididymis by epididymosomes transfer [57] and in the acquisition of fertilizing ability, since it is present in a higher amount in bulls with high fertility rates compared to those that are subfertile [87]. This fact is confirmed for its role in human (P34H), whose expression was decreased in a significant proportion of men investigated for male infertility [85, 147]. …”

Section: Molecular Markers Of Bull Fertilitymentioning

confidence: 99%

Post Testicular Sperm Maturational Changes in the Bull: Important Role of the Epididymosomes and Prostasomes

Caballero

Frenette

Sullivan

2011

Veterinary Medicine International

Self Cite

View full text Add to dashboard Cite

After spermatogenesis, testicular spermatozoa are not able to fertilize an oocyte, they must undergo sequential maturational processes. Part of these essential processes occurs during the transit of the spermatozoa through the male reproductive tract. Since the sperm become silent in terms of translation and transcription at the testicular level, all the maturational changes that take place on them are dependent on the interaction of spermatozoa with epididymal and accessory gland fluids. During the last decades, reproductive biotechnologies applied to bovine species have advanced significantly. The knowledge of the bull reproductive physiology is really important for the improvement of these techniques and the development of new ones. This paper focuses on the importance of the sperm interaction with the male reproductive fluids to acquire the fertilizing ability, with special attention to the role of the membranous vesicles present in those fluids and the recent mechanisms of protein acquisition during sperm maturation.

show abstract

Epididymal P34H protein deficiency in men evaluated for infertility

Cited by 32 publications

References 23 publications

Clusterin Facilitates Exchange of Glycosyl Phosphatidylinositol-Linked SPAM1 Between Reproductive Luminal Fluids and Mouse and Human Sperm Membranes1

Clusterin Facilitates Exchange of Glycosyl Phosphatidylinositol-Linked SPAM1 Between Reproductive Luminal Fluids and Mouse and Human Sperm Membranes1

Novel epididymal proteins as targets for the development of post-testicular male contraception

Post Testicular Sperm Maturational Changes in the Bull: Important Role of the Epididymosomes and Prostasomes

Contact Info

Product

Resources

About