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

By: Daniel E. Henao, Angela Patricia Cadavid and Walter Cardona Mayalowast

Published online: 01 December 2011

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Tollner TL, Venners SA, Hollox EJ, et alSci Transl Med 2011;3:92ra65Experts’ summary:Tollner and colleagues cogently demonstrate that a common variant in the defensin, beta 126 (DEFB126) gene, the “del” variant—a two-nucleotide omission that results in a reading frame shift and generates a nonstop messenger RNA—alters sperm function and can reduce male fertility significantly.

Although no association was found between this polymorphism and semen volume, sperm density, sperm motility, or total motile count, sperm from donors with the DEFB126 genotype (del/del) consistently showed reduction in binding sites for Agaricus bisporus lectin-associated fluorescence and reduced ability to penetrate a surrogate of cervical mucus (hyaluronic acid) compared with sperm from men with either of two others genotypes (wt/wt or wt/del).

Furthermore, the authors found high frequency of a DEFB126 deletion variant among several population cohorts worldwide (allele frequency: 0.44–0.61). Finally, they observed the association between the presence of this polymorphism and fertility (live birth outcome), finding that the odds of pregnancy (ratio of pregnant to nonpregnant) among couples in which males had the del/del genotype were 60% of those observed for couples in which males had the other two genotypes (odds ratio: 0.6; 95% confidence interval, 0.4–0.9; p=0.029).

In conclusion, the authors show that sperm from del/del homozygotes (male) lack an important component of their glycoprotein coat (O-linked oligosaccharides on β-defensin protein), altering its ability to penetrate a surrogate for cervical mucus, and that these men have less chance to conceive a live birth.Experts’ comment:The authors show interesting results about the role of DEFB126 in fertility outcomes and plausible mechanisms to explain them.

Given that the mechanism underlying the impaired reproductive function in these couples could be related to an altered ability of the sperm to penetrate the cervical mucus, fertility-doctor consultants could guide couples to consider alternative reproductive treatments (ie, in vitro fertilization and intracytoplasmic sperm injection). Nonetheless, it is important to recognize that reduced penetration of cervical mucus might not be the only reason that del/del homozygotes (male) have lower fertility [1]; other functional tests could be used to further evaluate the fertility status of these men [2].

It is remarkable that evaluating this polymorphism among infertile couples is important, and always establishing new causes that could explain infertility is important.

We found it particularly interesting that even though statistical difference was found between the groups, the proportion of fertile men in the del/del-variant group (71%, 72 of 102) was very similar to those in the others two groups (wt/wt: 82%, 128 of 156; wt/del: 80%, 200 of 251). Recognizing this important advance in our understanding of infertility, we still have a long journey to fully comprehend the mechanisms that underlie this problem in couples.

Conflicts of interest

The authors have nothing to disclose.


  • [1] S. Rozen. Defending male fertility. Sci Transl Med. 2011;3:92ps31 Crossref.
  • [2] W.D. Cardona Maya, J.A. Berdugo Gutierrez, J. de los Rios, A.P. Cadavid Jaramillo. Functional evaluation of sperm in Colombian fertile men. Arch Esp Urol. 2007;60:827-831


Grupo Reproducción, Universidad de Antioquia, Medellín, Colombia

lowast Corresponding author.