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Title: A Common Mutation in the Defensin DEFB126 Causes Impaired Sperm Function and Subfertility
Authors: Tollner, Theodore L.
Venners, Scott A.
Hollox, Edward J.
Yudin, Ashley I.
Liu, Xue
Tang, Genfu
Xing, Houxun
Kays, Robert J.
Lau, Tsang
Overstreet, James W.
Xu, Xiping
Bevins, Charles L.
Cherr, Gary N.
First Published: 20-Jul-2011
Citation: Science Translational Medicine, 2011, 3 (92), p. 92ra65
Abstract: 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 two-nucleotide deletion in the open reading frame, which generates an abnormal mRNA. The allele frequency of this variant sequence was 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 a wt/wt genotype, suggesting an altered sperm glycocalyx with fewer O-linked oligosaccharides in del/del men. Moreover, sperm from del/del carriers exhibited an 84% reduction in the rate of penetration of a hyaluronic acid gel, a surrogate for cervical mucus, compared to the other genotypes. This reduction in sperm performance in hyaluronic acid gels was not a result of decreased progressive motility (average curvilinear velocity) or morphological deficits. Nevertheless, DEFB126 genotype and lectin binding were correlated with sperm 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 effect of impaired reproductive function, will allow a better understanding, clinical evaluation, and possibly treatment of human infertility.
DOI Link: 10.1126/scitranslmed.3002289
ISSN: 1946-6234
eISSN: 1946-6242
Version: Post-print
Status: Peer reviewed
Type: Journal Article
Rights: Copyright © 2011, American Association for the Advancement of Science. Deposited with reference to the publisher’s archiving policy available on the SHERPA/RoMEO website.
Appears in Collections:Published Articles, Dept. of Genetics

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