Role of Antisperm Antibodies in Infertility, Pregnancy, and Potential for Contraceptive and Antifertility Vaccine Designs: Research Progress and Pioneering Vision

Abstract

Sperm of humans, non-human primates, and other mammalian subjects is considered to be antigenic. The effect of changes in autoimmunity on reproductive cells such as spermatozoa and oocytes play a critical but indistinct role in fertility. Antisperm antibodies (ASAs) are invariably present in both females and males. However, the degree of ASA occurrence may vary according to individual and gender. Although the extent of infertility due to ASAs alone is yet to be determined, it has been found in almost 9–12% of patients who are infertile due to different causes. Postcoital presence of spermatozoa in the reproductive tract of women is not a contributory factor in ASA generation. However, ASA generation may be induced by trauma to the vaginal mucosa, or by anal or oral sex resulting in the deposition of sperm inside the digestive tract. It is strongly believed that, in humans and other species, at least some antibodies may bind to sperm antigens, causing infertility. This form of infertility is termed as immunological infertility, which may be accompanied by impairment of fertility, even in individuals with normozoospermia. Researchers target ASAs for two major reasons: (i) to elucidate the association between ASAs and infertility, the reason ASAs causes infertility, and the mechanism underlying ASA-mediated infertility; and (ii) to assess the potential of ASAs as a contraceptive in humans in case ASAs influences infertility. Therefore, this review explores the potential application of ASAs in the development of anti-spermatozoa vaccines for contraceptive purposes. The usefulness of ASAs for diagnosing obstructive azoospermia, salpingitis, and oligoasthenoteratozoospermia has been reviewed extensively. Important patents pertaining to potential candidates for spermatozoa-derived vaccines that may be utilized as contraceptives are discussed in depth. Antifertility vaccines, as well as treatments for ASA-related infertility, are also highlighted. This review will address many unresolved issues regarding mechanisms involving ASAs in the diagnosis, as well as prognoses, of male infertility. More documented scientific reports are cited to support the mechanisms underlying the potential role of ASA in infertility. The usefulness of sperm antigens or ASAs (recombinant) in human and wild or captive animal contraceptive vaccines has been revealed through research but is yet to be validated via clinical testing.

Pathomechanisms of Autoimmune Based Testicular Inflammation

“…However, it is relevant that focal lymphocytic infiltrations have been detected in 25-30% of testicular biopsies from infertile patients (8,9). Anti-sperm antibodies (ASA) have been mainly detected in patients with obstructive azoospermia (10). However, there is so far no close association between ASA and male genital tract inflammation (11,12) except for some reports associating ASA with idiopathic granulomatous orchitis (13,14) and a history of epididymitis/orchitis (15).…”

The Relationship between Seminal Fluid Hyperviscosity and Oxidative Stress: A Systematic Review

“…The anti-sperm antibodies are formed against antigenic proteins following the exposure of these proteins to immune cells [37]. The testes are an immunologically privileged site because of the presence of the blood-testis barrier that protects the autoantigenic germ cells from immune attacks [38].…”

“…However, several factors, including environmental toxicants or genetic disorders can impair the integrity of the blood-testis barrier [38]. In men, the risk of the development of anti-sperm antibodies increases after blood-testis barrier breakdown, surgical trauma, infections, testicular tumor, and varicocele [37]. MAGI can cause the formation of anti-sperm antibodies yielding an autoimmunity response [39,40].…”

“…Moreover, an inverse relationship between the titer of spermatozoa bound to anti-sperm antibodies and the fertilizing capability of sperm has been shown [36]. However, some researchers reported that there was no association between anti-sperm antibodies and the pregnancy rate [37]. The unclear role of anti-sperm antibodies in human fertility could reflect the inadequacies of the diagnostic techniques that detect antibody binding to spermatozoa but do not evaluate their antigenic specificities [36].…”

Pathogenesis of Autoimmune Male Infertility: Juxtacrine, Paracrine and Endocrine Deregulation

“…In recent years, infertility has become a global health problem [1]. Increasing number of men suffer from impaired fertility, while the incidence of the male factor of infertility reaches 30-50% in infertile couples [2][3][4][5][6][7]. The reproductive potential of the world male population is declining steadily and there is no tendency to improvement [7][8][9][10][11].…”