Human reproductive failure I: Immunological factors

Abstract

Human reproductive failure may be a consequence of aberrant expression of immunological factors during pregnancy. Although the relative importance of immunological factors in human reproduction remains controversial, substantial evidence suggests that human leukocyte antigens (HLA), antisperm antibodies, integrins, the leukaemia inhibitory factor (LIF), cytokines, antiphospholipid antibodies, endometrial adhesion factors, mucins (MUC1) and uterine natural killer cells contribute to reproductive failure. In contrast, fewer data support the roles of anti-trophoblast antibodies, anti-endometrial antibodies, T-cells, peripheral natural killer cells, anti-HLA antibodies, blocking antibodies and suppressor cells in reproductive failure. Although immunological factors involved in reproductive failure have been studied traditionally using assays for antibodies and/or antigens, detailed research on these factors demonstrates conflicting results in humans. Maternal and fetal immunology is also difficult to investigate in humans. For these reasons, molecular assays may serve as a valuable alternative to investigate how the immune system affects reproductive outcome. In Part I of this review, immunological factors involved in human reproductive failure are summarized and critically evaluated. Immunogenetic and interacting factors in human reproductive failure will be summarized and evaluated in Part II.

Genome-wide miRNA profiling of villus and decidua of recurrent spontaneous abortion patients

“…Although the relative importance of immunological factors in human reproduction remains controversial, substantial evidence suggests that the leukaemia inhibitory factor (LIF), progesterone-induced blocking factor (PIBF), HLA-DPB1 and CD69 contribute to RSA. From targets' prediction data, we found upregulated miRNAs (hsa-miR-519a-1 and hsa-miR-520h) in decidua and low expressed miRNA (hsa-miR-520f) in villus of RSA patients, all target to LIF (Supplementary Table 3, see section on supplementary data given at the end of this article), substantial evidence suggests that LIF contributes to reproductive failure (Choudhury & Knapp 2001). In decidua, PIBF is known as a target gene of hsa-miR 520h (Supplementary Table 3), and PIBF can mediate progesterone-induced suppression of decidual lymphocyte cytotoxicity (Laskarin et al 2002).…”

The hidden benefits of sex: Evidence for MHC‐associated mate choice in primate societies

“…These molecules, partially encoded by the paternal haplotype, may represent 'non-self' for the mother but nevertheless contribute to the regulation of the maternal immune response throughout gestation [76]. Consequently, post-insemination MHC-dependent selection may be of particular importance in primates, and account for the higher probability of pregnancy failure reported for couples displaying above-average MHC similarity in humans [77] and macaques [78].…”

Immunogenetic contributions to recurrent pregnancy loss

“…There they express IL-10, TGFβ, and TNFα [10]. TNF-α is produced by all CD4+ T cells [11,[72][73][74][75]. IL-10 inhibits macrophages and Th1 cell proliferation [76,77].…”