Can the Decreased Expression of Human Leukocyte Antigen Class Ⅰ and Ⅱ by Spermatozoa Lead to Recurrent Spontaneous Abortion?

Abstract

Scan to discover online Background & Objective: Unexplained recurrent spontaneous abortion (URSA) is defined as an unknown cause of occurrence of three or more clinically detectable pregnancy losses before 20 weeks of gestation, but it occurs presumably as a result of the immune system dysfunctions. We supposed that the disruption of semen or spermatozoa might be responsible for the dysfunction of the immune system in women with URSA. Semen and spermatozoa (as antigens) induce female reproductive tract (FRT) immunity. This stimulated immunity is necessary for pregnancy occurrence. The disruption of semen or spermatozoa can be a result of altering a variety of surface molecules on spermatozoa, especially polymorphic human leukocyte antigen (HLA) molecules or antigens. Despite the importance of HLA antigens in reproduction, to the best of our knowledge, no one has studied the relation of HLA expression between spermatozoa and URSA. Therefore, this paper aims to assess this relation. Methods: Semen samples were collected from 15 URSA couples and 20 normal couples. After purification of normal spermatozoa, the HLA class I and II expressions were evaluated by flow cytometry methods. Results: Results showed that the expression of both HLA class I and II by spermatozoa, in URSA couples, was significantly less than the control couples. Conclusion: The decreased expression of polymorphic HLA class Ⅰ and Ⅱ by spermatozoa can be related to URSA occurrence.

Lack of anti-paternal cytotoxic antibody production in the presence of spermatozoa in recurrent spontaneous abortion couples in contrast to fertile couples: a pilot study

“…Experiments on serum APCA have shown that APCA is directed to paternal HLA [9,12]. We recently showed that HLA class I & II molecules are expressed on spermatozoa [26] and we revealed a decreased expression of these molecules on spermatozoa obtained from men whose wives suffer from RSA [7]. This result is accordant to our hypothesis that APCA production is induced by HLA molecules on spermatozoa.…”

“…Our recent studies offer new evidence for the relation between abnormality in the expression of spermatozoa surface molecules and RSA. We show decreased expression of HLA class I & II [7] and toll-like receptor4 (TLR4) on the husband's spermatozoa from couples suffering from RSA [8]. We show that the husband's spermatozoa could induce maternal peripheral blood mononuclear cells (PBMCs) for the production of anti-paternal cytotoxic antibody (APCA) (https://cell journal.org/journal/article/abstract/7157).…”

The effect of probiotics on immunogenicity of spermatozoa in couples suffering from recurrent spontaneous abortion

“…We showed that the probiotic treatment of spermatozoa results in an increase of HLA class I in the RSA and fertile groups and an increase of HLA class II in the fertile group, but no significant effect on HLA class II in RSA group. In the present study and our recent study [ 21 ], we showed that HLA class I & II expression on spermatozoa is decreased in men whose female partners suffered from RSA (RSA couples). The role of HLA on spermatozoa in reproduction has not yet been determined, but we think that the presence of these molecules on spermatozoa is needed to stimulate immunity in the FRT and consequently to achieve successful pregnancy.…”

“…Impairment of spermatozoa antigenicity can lead to impaired immunity to paternal antigens and consequently pregnancy complications such as RSA [ 2 , 21 ]. Impairment of spermatozoa antigenicity may be a result of interaction with inappropriate microbiota composition.…”

“…Recently, we showed decreased expression of HLA class I & II on spermatozoa in men whose wives suffer from RSA [ 21 ]. Therefore, the cause of the absence or reduction of APCA in RSA women may be decreased expression of HLA class I & II by the husband’s spermatozoa.…”