Immunological Tolerance, Pregnancy, and Preeclampsia: The Roles of Semen Microbes and the Father†

Abstract

Although it is widely considered, in many cases, to involve two separable stages (poor placentation followed by oxidative stress/inflammation), the precise originating causes of preeclampsia (PE) remain elusive. We have previously brought together some of the considerable evidence that a (dormant) microbial component is commonly a significant part of its etiology. However, apart from recognizing, consistent with this view, that the many inflammatory markers of PE are also increased in infection, we had little to say about immunity, whether innate or adaptive. In addition, we focused on the gut, oral and female urinary tract microbiomes as the main sources of the infection. We here marshall further evidence for an infectious component in PE, focusing on the immunological tolerance characteristic of pregnancy, and the well-established fact that increased exposure to the father’s semen assists this immunological tolerance. As well as these benefits, however, semen is not sterile, microbial tolerance mechanisms may exist, and we also review the evidence that semen may be responsible for inoculating the developing conceptus (and maybe the placenta) with microbes, not all of which are benign. It is suggested that when they are not, this may be a significant cause of PE. A variety of epidemiological and other evidence is entirely consistent with this, not least correlations between semen infection, infertility and PE. Our view also leads to a series of other, testable predictions. Overall, we argue for a significant paternal role in the development of PE through microbial infection of the mother via insemination.

The biology of ergothioneine, an antioxidant nutraceutical

“…Interestingly, ERG is also present in seminal fluid (394)(395)(396) and human breast milk (6) . Any possible correlation with male fertility (397) seems not to have been established, though there were no negative effects (398) , and ERG improved oocyte quality and maturation in cows and sheep (399) . ERG is also present in eye lens, where its concentration is lower in individuals with cataracts (400) .…”

Inflammasomes—A Molecular Link for Altered Immunoregulation and Inflammation Mediated Vascular Dysfunction in Preeclampsia

“…Several studies have also reported that there is a role for the immune system during pregnancy reacting against and/or tolerating the paternal antigens of the conceptus [68][69][70][71][72][73][74]. It was suggested that that increased exposure to the father's semen assists this immunological tolerance [68]. In addition to these benefits, although semen is not sterile, microbial tolerance mechanisms may exist [75].…”

“…In addition to these benefits, although semen is not sterile, microbial tolerance mechanisms may exist [75]. Recent reports [68,75] have shown evidence that semen may be responsible for inoculating the developing conceptus, including the placenta with microbes, not all of which are infectious. It was suggested that when they are infectious, it may cause PE [68].…”

The role of immunity in the pathogenesis and development of pre‐eclampsia

“…For example, PE is reported to be more prevalent in patients with pre‐existing periodontitis . In addition, semen is far from sterile and commonly infected with microbes, which might be the origin of infection associated with PE . Furthermore, studies have shown the presence of microbes in the placenta, amniotic fluid and vagina, and these bacteria vary greatly in PE .…”