Multifunctional glycoprotein DEFB126—a curious story of defensin-clad spermatozoa

Abstract

During maturation, the surface of mammalian spermatozoa undergoes dramatic changes leading to the acquisition of properties vital for survival and performance in the female reproductive tract. A prominent change is the addition to the sperm surface of an atypical β-defensin polypeptide. In primates, the β-defensin DEFB126 becomes adsorbed to the entire sperm surface as spermatozoa move through the epididymal duct. DEFB126 has a conserved β-defensin core and a unique long glycosylated peptide tail. The carbohydrates of this domain contribute substantially to the sperm glycocalyx. DEFB126 is critical for efficient transport of sperm in the female reproductive tract, preventing their recognition by the female immune system, and might facilitate the delivery of capacitated sperm to the site of fertilization. A newly discovered dinucleotide deletion in the human DEFB126 gene is unusually common in diverse populations and results in a null allele. Predictably, men who are homozygous for the deletion produce sperm with an altered glycocalyx and impaired function, and have reduced fertility. Insights into the biology of DEFB126 are contributing to a better understanding of reproductive fitness in humans, as well as the development of diagnostics and therapeutics for male infertility.

Neisseria gonorrhoeae Defense against Human Neutrophils and Host-derived Antimicrobials

“…βD22 orthologs have also been identified in mouse and primates (Yudin et al, 2008;Tollner et al, 2012). Human βD126 and rat βD22 share 45% identity (E-value 4E -18 ; NCBI Blast).…”

“…The β-defensin domain of human and rat βD22 has been shown to have antimicrobial activity against the fungus Candida albicans, the gram-negative bacterium E. coli, and the gram-positive bacterium Staphylococcus aureus (Diao et al, 2011;Liu et al, 2013). βD22 is preferentially expressed in the reproductive tract of the host (Tollner et al, 2012). This site is a prominent environmental niche for Neisseria gonorrhoeae and other sexually transmitted pathogens.…”

“…Human βD126 and rat βD22 share 45% identity (E-value 4E -18 ; NCBI Blast). βD22 is secreted in the epididymis and coats the sperm glycocalyx, an immunoprotective scaffold composed of surface-associated oligosaccharides (Rao, 2002;Zanich, 2003;Tollner et al, 2012). The expression pattern of βD22 and its ability to coat sperm are maintained across species (Tollner et al, 2012).…”

“…βD22 facilitates attachment of sperm to the oviductal epithelium, enhances capacitation and sperm-egg interactions within the female reproductive tract, and protects sperm from immune recognition (Yudin et al, 2008;Tollner et al, 2012). The β-defensin domain of human and rat βD22 has been shown to have antimicrobial activity against the fungus Candida albicans, the gram-negative bacterium E. coli, and the gram-positive bacterium Staphylococcus aureus (Diao et al, 2011;Liu et al, 2013).…”

“…The defensin motif of βD22 contains the six conserved cysteine residues that are characteristic for β-defensins ( Figure 4B). The lectin-like motif is glycosylated and contributes to the glycocalyx of sperm (Tollner et al, 2012).…”