Beta-defensins as marker for male fertility: a comprehensive review

Abstract Bovine male fertility in animals has a direct impact on the productivity of dairy herds. The epididymal sperm maturations involve extensive sperm surface modifications to gain the fertilizing ability, especially by absorptions of the plethora of biomolecules, including glycoprotein beta-defensins (BDs), enzymes, organic ions, protein, and phospholipids. Defensins are broad-range nonspecific antimicrobial peptides that exhibit strong relations with innate and adaptive immunity, but their roles in male fertility are relatively recently identified. In the course of evolution, BD genes give rise to different clusters with specific functions, especially reproductive functions, by undergoing duplications and nonsynonymous mutations. BD polymorphisms have been reported with milk compositions, disease resistance, and antimicrobial activities. However, in recent decades, the link of BD polymorphisms with fertility has emerged as an appealing improvement of reproductive performance such as sperm motility, membrane integrity, cervical mucus penetration, evading of uterus immunosurveillance, oviduct cell attachment, and egg recognition. The reproductive-specific glycosylated BD class-A BDs (CA-BDs) have shown age- and sex-specific expressions in male reproductive organs, signifying their physiological pleiotropism, especially in the sperm maturation and sperm transport in the female reproductive tract. By considering adult male reproductive organ-specific BD expressions, importance in sperm functionalities, and bioinformatic analysis, we have selected two bovine BBD126 and BBD129 genes as novel potential biomarkers of bovine male fertility. Despite the importance of BDs, however, genomic characterization of most BD genes across most livestock and nonmodel organisms remains predictive/incomplete. The current review discusses our understanding of BD pleiotropic functions, polymorphism, and genomic structural attributes concerning the fertilizability of the male gamete in dairy animals. Graphical Abstract (A) Sperm epididymis maturation and antimicrobial activity—BDs are secreted by epithelial cells of epididymis which facilitate or prepare sperm for fertilizable and protect sperm from reproductive microbial infection. (B) Epididymis maturation for immune protection of male MRT and FRT—BDs are rich in glycosylation which provide a thick coat on outer plasma membrane masking important proteins/antigens from immune recognition of MRT and FRT. (C) Epididymis sperm motility—BDs interact with sperm plasma membrane ion channels and regulate calcium ion which help in sperm motility. (D) FRT sperm-cervical mucus penetration—the negative charge of BDs help sperm to pass cervical mucus by creating a repulsion force between negatively charged mucin protein of cervix. (E) Cervix-uterine immunomodulator and immune-protectant—BDs mask sperm surface antigen which help sperm to evade FRT immune surveillance. (F) FRT sperm-oviductal epithelial cells binding (sperm reservoir formation)—the carbohydrates present at the end terminal of glycosylated BDs help sperm to interact with oviduct epithelial cells lead to sperm reservoir formation. (G) FRT sperm capacitation and unshielding of hidden proteins—the removal of BDs from sperm surface lead to change in sperm membrane and capacitation. (H) egg–sperm interactions—unshielding of BDs leads to unmasking of hidden protein that is very essential for the egg recognition and penetration.