Release of DEFB126 from macaque sperm and completion of capacitation are triggered by conditions that simulate periovulatory oviductal fluid

Tollner, Theodore L.; VandeVoort, Catherine A.; Yudin, Ashley I.; Treece, Cathy A.; Overstreet, James W.; Cherr, Gary N.

doi:10.1002/mrd.20964

Cited by 9 publications

(12 citation statements)

References 96 publications

(103 reference statements)

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“…Studies in non-human primates have shown that DEFB126 is a major component of the sperm surface glycocalyx and is important for normal sperm function, including efficient sperm trafficking in the female reproductive tract (15, 16, 17, 18, 19, 45, 46). We now report that a mutation in human DEFB126 is common in each of several disparate population cohorts interrogated (allele frequency 0.44-0.61).…”

Section: Discussionmentioning

confidence: 99%

A Common Mutation in the Defensin DEFB126 Causes Impaired Sperm Function and Subfertility

et al. 2011

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A glycosylated polypeptide, β-defensin 126 (DEFB126), derived from the epididymis and adsorbed onto the sperm surface, has been implicated in immunoprotection and efficient movement of sperm in mucosal fluids of the female reproductive tract. Here, we report a sequence variant in DEFB126 that has a 2-nucleotide deletion in the open reading frame, which generates a non-stop mRNA. The allele frequency of this variant sequence is high in both a European (0.47) and a Chinese (0.45) population cohort. Binding of the Agaricus bisporus lectin to the sperm surface glycocalyx was significantly lower in men with the homozygous variant (del/del) genotype than in those with either a del/wt or wt/wt genotype, suggesting an altered sperm glycocalyx with fewer O-linked oligosaccharides in del/del men. Moreover, sperm from the del/del donors exhibited an 84% reduction in the rate of penetration of a hyaluronic acid (HA) gel, a surrogate for cervical mucus, compared to the other genotypes. This reduction in sperm performance in HA gels was not a result of decreased progressive motility (average curvilinear velocity) or morphological deficits. However, DEFB126 genotype and lectin binding were highly correlated with performance in the penetration assays. In a prospective cohort study of newly married couples who were trying to conceive by natural means, couples were less likely to become pregnant and took longer to achieve a live birth if the male partner was homozygous for the variant sequence. This common sequence variation in DEFB126, and its apparent cause of impaired reproductive function, provides an opportunity to better understand, clinically evaluate, and possibly treat human infertility.

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Section: Discussionmentioning

confidence: 99%

A Common Mutation in the Defensin DEFB126 Causes Impaired Sperm Function and Subfertility

et al. 2011

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“…It is the negative charges on DEFB126 on the sperm surface that allow sperm to move through the cervical mucus, which is enriched in anionic glycosaminoglycans 9 . Upon capacitation, DEFB126 is released from the sperm surface 9 42 . If del / del mutation results the loss of DEFB126, the level of sialic acid has to be reduced.…”

Section: Discussionmentioning

confidence: 99%

Lectin binding of human sperm associates with DEFB126 mutation and serves as a potential biomarker for subfertility

Xin

Cheng

Diao

et al. 2016

Sci Rep

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Coating on the sperm surface, glycocalyx, plays a key role in sperm motility, maturation and fertilization. A comprehensive profile of sperm surface glycans will greatly facilitate both basic researches and clinical studies. Because of the capability of recognizing different glycan moieties, lectins are widely used in glycobiology. However, lacking high-throughput technology, limited lectins have been reported for analyzing the glycan of human sperm. In this study, we employed a lectin microarray for profiling the surface glycans of human sperm, on which 54 out of 91 lectins showed positive binding. Based on this technique, we compared lectin binding profiling of sperm with homozygous DEFB126 mutation (del/del) with that of wild type (wt/wt). DEFB126 was reported to contribute to the sialylation on sperm surface and its homozygous mutation was related to male subfertility. Six lectins (Jacalin/AIA, GHA, ACL, MPL, VVL and ABA) were found to develop lower binding affinity to sperm with del/del. Further validation showed that these lectins, especially ABA and MPL, can be potential biomarkers for clinical diagnosis of subfertility due to the mutation of DEFB126. Our research provides insight into the detection of some unexplained male subfertility, and the lectin microarray is generally applicable for infertility/subfertility sperm biomarker discovery.

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“…Evidence for this possibility includes the observation that soluble oviductal factors enhance capacitation of bull sperm (Chian et al 1995). Also, incubating macaque sperm in medium containing the levels of bicarbonate and glucose found in periovulatory oviduct fluid capacitates the sperm and releases oviduct-binding DEFB126 from the sperm surface (Tollner et al 2009). …”

Section: Molecular Interactionsmentioning

confidence: 99%

Mammalian sperm interactions with the female reproductive tract

2015

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The mammalian female reproductive tract interacts with sperm in various ways in order to facilitate sperm migration to the egg while impeding migrations of pathogens into the tract, to keep sperm alive during the time between mating and ovulation, and to select the fittest sperm for fertilization. The two main types of interactions are physical and molecular. Physical interactions include the swimming responses of sperm to the microarchitecture of walls, to fluid flows, and to fluid viscoelasticity. When sperm encounter walls, they have a strong tendency to remain swimming along them. Sperm will also orient their swimming into gentle fluid flows. The female tract seems to use these tendencies of sperm to guide them to the site of fertilization. When sperm hyperactivate, they are better able to penetrate highly viscoelastic media, such as the cumulus matrix surrounding eggs. Molecular interactions include communications of sperm surface molecules with receptors on the epithelial lining of the tract. There is evidence that specific sperm surface molecules are required to enable sperm to pass through the uterotubal junction into the oviduct. When sperm reach the oviduct, most bind to the oviductal epithelium. This interaction holds sperm in a storage reservoir until ovulation and serves to maintain fertilization competence of stored sperm. When sperm are released from the reservoir, they detach from and re-attach to the epithelium repeatedly while ascending to the site of fertilization. We are only beginning to understand the communications that may pass between sperm and epithelium during these interactions.

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Release of DEFB126 from macaque sperm and completion of capacitation are triggered by conditions that simulate periovulatory oviductal fluid

Cited by 9 publications

References 96 publications

A Common Mutation in the Defensin DEFB126 Causes Impaired Sperm Function and Subfertility

A Common Mutation in the Defensin DEFB126 Causes Impaired Sperm Function and Subfertility

Lectin binding of human sperm associates with DEFB126 mutation and serves as a potential biomarker for subfertility

Mammalian sperm interactions with the female reproductive tract

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