β-defensins and the epididymis: contrasting influences of prenatal, postnatal, and adult scenarios

Abstract

β-defensins are components of host defense, with antimicrobial and pleiotropic immuno-modulatory properties. Research over the last 15 years has demonstrated abundant expression of a variety of β-defensins in the postnatal epididymis of different species. A gradient of region- and cell-specific expression of these proteins is observed in the epithelium of the postnatal epididymis. Their secretion into the luminal fluid and binding to spermatozoa as they travel along the epididymis has suggested their involvement in reproduction-specific tasks. Therefore, continuous attention has been given to various β-defensins for their role in sperm function and fertility. Although β-defensins are largely dependent on androgens, the underlying mechanisms regulating their expression and function in the epididymis are not well understood. Recent investigation has pointed out to a new and interesting scenario where β-defensins emerge with a different expression pattern in the Wolffian duct, the embryonic precursor of the epididymis, as opposed to the adult epididymis, thereby redefining the concept concerning the multifunctional roles of β-defensins in the developing epididymis. In this review, we summarize some current views of β-defensins in the epididymis highlighting our most recent data and speculations on their role in the developing epididymis during the prenatal-to-postnatal transition, bringing attention to the many unanswered questions in this research area that may contribute to a better understanding of epididymal biology and male fertility.

Novel role of proton-secreting epithelial cells in sperm maturation and mucosal immunity

“…Interestingly, CCs express components of immune activation in the epididymis. Among these mediators, we found several β-defensins (Defbs), a major subfamily of host defense peptides that are abundant in the epididymis (Johnston et al, 2007;Ribeiro et al, 2016). Thus, the current study now positions CCs as an important source of several Defbs, indicating that they may play a constitutive role in monitoring epididymal health.…”

An atlas of cell types in the mouse epididymis and vas deferens

“…As is clear from many prior studies of epididymal gene regulation ( Guyonnet et al, 2009 ; Hales et al, 1980 ; Hall et al, 2007 ; Jelinsky et al, 2007 ; Jervis and Robaire, 2001 ; Johnston et al, 2005 ; Papp et al, 1995 ; Ribeiro et al, 2016 ; Thimon et al, 2007 ), the genes that define principal cells from any given segment tend to be members of multi-gene families encoded in genomic clusters of many paralogous genes ( Figure 3D–E , Figure 3—figure supplement 2 ). These clusters include gene families encoding serine protease inhibitors, antimicrobial defensin peptides, cysteine-rich peptides involved in glycocalyx maturation, small molecule-binding lipocalins, aldo-keto reductases, and RNaseA family members.…”

“…However, the most notable feature of region-specific gene regulation in the epididymis is the segmental expression of individual members of several large multi-gene families that are organized in genomic clusters, including β-defensins, aldo-keto reductases, lipocalins, serine protease inhibitors, and RNases ( Figure 3—figure supplement 2 ). The activities encoded by these gene clusters encompass many well-characterized functions of the epididymis, as for example it has long been known that the sperm membrane and glycocalyx are extensively remodeled in the epididymis ( Bernal et al, 1980 ; Tecle and Gagneux, 2015 ; Yanagimachi et al, 1972 ), while the wide array of antimicrobial peptides presumably serve to insulate the testis from ascending infections ( Dorin and Barratt, 2014 ; Gregory and Cyr, 2014 ; Hall et al, 2007 ; Ribeiro et al, 2016 ). Sperm also undergo elaborate redox remodeling during their time in the epididymis, with extensive cysteine oxidation resulting in disulfide crosslinks in the genome-packaging protamines and many other proteins ( Calvin and Bedford, 1971 ; Dias et al, 2014 ; Ijiri et al, 2014 ; Saowaros and Panyim, 1979 ).…”

Comparative RNA-Seq Analysis of Differentially Expressed Genes in the Epididymides of Yak and Cattleyak

“…Among the top 30 DEGs, majority belonged to ß -defensins members of gene family i.e DEFB129 (defensin beta 129), DEFB124 (Defensin. beta 124), DEFB122A (beta-defensin 122a), DEFB122 (beta-defensin 122) and CST11(cystatin-11 precursor), CLEC4D (C-type lectin domain family 4 member D), LY6G5C (lymphocyte antigen 6 family member G5C), LY6G5B (lymphocyte antigen 6 family member G5B), CLEC4D (C-type lectin domain family 4 member D) and UBQLN2 (ubiquilin 2) were all associated with antimicrobial activity, anti-mycobacterial immunity, sperm protection, motility and auto-immune responses [30][31][32][33][34].…”