Spermatozoa are almost unique among cells in that they must survive transplantation into a foreign host in order to perform their physiological role. The biggest hurdle to overcome is innate immune defence that will target the invaders in the female genital tract. Complement is a major player in innate immunity and is present in the female genital tract. Spermatozoa must therefore evade complement attack if they are to reach their goal. Complement evasion is achieved by the presence of complement regulators both in seminal plasma and on the spermatozoa. Here we discuss the parts played by complement and complement regulators in permitting spermatozoa to survive long enough to reach the oocyte, in clearance of the excess spermatozoa that have outlived their usefulness and in aiding activation of spermatozoa to engage the oocyte. In particular, we focus on the unique distribution patterns of complement regulators on spermatozoa, patterns that strongly suggest roles in spermatozoal development and oocyte binding. An understanding of these roles will inform studies of their contribution to fertility and infertility in man.
"Sperm contain an array of CD antigens in addition to CD46 including CD55, CD59, and CD109. As stated previously , rodent CD46 regulates the acrosome reaction and has also been suggested to impact sperm-egg binding [Harris et al. 2006; Inoue et al. 2003]. CD55 and CD59 have been postulated to supplement sperm protection from complement [Anderson et al. 1993; Clift et al. 2009b; Inoue et al. 2003; Johnson et al. 2007]. "
[Show abstract][Hide abstract] ABSTRACT: Ongoing proteomic analyses are providing a wealth of new data on the composition of the sperm proteome across a range of mammals and other taxa. Although molecular evolution and functional genomic analyses of the proteome have only begun recently, we now broadly understand the molecular composition of sperm. Systems level analysis has revealed a variety of molecular insights into sperm evolution and function, including a remarkable diversity of immunity-related proteins within the proteome. Using existing mammalian sperm proteomes as a starting point, we provide an overview of this important class of sperm proteins and what is known about their function in sperm maturation, sperm quality, sperm competition, and fertilization. The recent observation that many sperm immunity proteins are rapidly evolving, presumably under the influence of positive selection, suggests that they may be responding not only to selection associated with host immunity defense but also with pleiotropic functions in sperm. In addition to the documented role of sperm in the mediation of female immune response, we propose that the fundamental mechanisms involved in cell-cell recognition and binding in both immune processes and fertilization may underlie the multi-functionality of proteins in immunity and reproductive systems.
Systems biology in reproductive medicine 08/2012; 58(4):218-28. DOI:10.3109/19396368.2012.700442 · 1.60 Impact Factor
"In addition, CD46 has been implicated in the modulation of T-cell functions (Marie et al., 2002), generation of regulatory T-cells (Kemper et al., 2003), and control of interferon (IFN) production (Katayama et al., 2000). CD46 is also important during fertilization – it presumably promotes sperm–egg interaction (Riley-Vargas et al., 2004, 2005; Harris et al., 2006). CD46 exists in multiple isoforms, which are generated by alternative splicing of a single gene. "
[Show abstract][Hide abstract] ABSTRACT: Morbilliviruses, which include measles virus (MeV), canine distemper virus, and rinderpest virus, are among the most important pathogens in their respective hosts and cause severe syndromes. Morbilliviruses are enveloped viruses with two envelope proteins, one of which is hemagglutinin (H) protein, which plays a role in binding to cellular receptors. During morbillivirus infection, the virus initially targets lymphoid cells and replicates efficiently in the lymph nodes. The principal cellular receptor for morbillivirus is signaling lymphocyte activation molecule (SLAM, also called CD150), which is exclusively expressed on immune cells. This feature reflects the strong lymphoid cell tropism and viral spread in the infected body. Morbillivirus infection, however, affects various tissues in the body, including the lung, kidney, gastrointestinal tract, vascular endothelium, and brain. Thus, other receptors for morbilliviruses in addition to SLAM might exist. Recently, nectin-4 has been identified as a novel epithelial cell receptor for MeV. The expression of nectin-4 is localized to polarized epithelial cells, and this localization supports the notion of cell tropism since MeV also grows well in the epithelial cells of the respiratory tract. Although two major receptors for lymphoid and epithelial cells in natural infection have been identified, morbillivirus can still infect many other types of cells with low infectivity, suggesting the existence of inefficient but ubiquitously expressed receptors. We have identified other molecules that are implicated in morbillivirus infection of SLAM-negative cells by alternative mechanisms. These findings indicate that morbillivirus utilizes multiple pathways for establishment of infection. These studies will advance our understanding of morbillivirus tropism and pathogenesis.
Frontiers in Microbiology 03/2012; 3:75. DOI:10.3389/fmicb.2012.00075 · 3.99 Impact Factor
"testis environment could be sufficient to provide protection to sperm antigens throughout the male reproductive tract, under normal conditions. However, a more prominent role could exist for complement inhibitors in the epididymal epithelium and sperm than in the seminiferous epithelium (Harris et al, 2006; Mizuno et al, 2006; Ito et al, 2007), which could reflect the more ready access of immunoglobulins to the lumen of the epididymal duct (Weininger et al, 1982; Yule et al, 1988; Beagley et al, 1998; Knee et al, 2005). "
[Show abstract][Hide abstract] ABSTRACT: The ability of spermatogenic cells to evade the host immune system and the ability of systemic inflammation to inhibit male reproductive function represent two of the most intriguing conundrums of male reproduction. Clearly, an understanding of the underlying immunology of the male reproductive tract is crucial to resolving these superficially incompatible observations. One important consideration must be the very different immunological environments of the testis, where sperm develop, and the epididymis, where sperm mature and are stored. Compared with the elaborate blood-testis barrier, the tight junctions of the epididymis are much less effective. Unlike the seminiferous epithelium, immune cells are commonly observed within the epithelium, and can even be found within the lumen, of the epididymis. Crucially, there is little evidence for extended allograft survival (immune privilege) in the epididymis, as it exists in the testis, and the epididymis is much more susceptible to loss of immune tolerance. Moreover, the incidence of epididymitis is considerably greater than that of orchitis in humans, and susceptibility to sperm antibody formation after damage to the epididymis or vas deferens increases with increasing distance of the damage from the testis. Although we still know relatively little about testicular immunity, we know less about the interactions between the epididymis and the immune system. Given that the epididymis appears to be more susceptible to inflammation and immune reactions than the testis, and thereby represents the weaker link in protecting developing sperm from the immune system, it is probably time this imbalance in knowledge was addressed.
Journal of Andrology 07/2011; 32(6):625-40. DOI:10.2164/jandrol.111.012989 · 2.47 Impact Factor
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