The Paternal Contribution to Fetal Tolerance

Abstract

Recognition of foreign paternal antigens expressed in the semi-allogeneic fetus by maternal immune cells is a requirement for successful pregnancy. However, despite intensive research activity during the last decades, the precise mechanisms contributing to the acceptance of the paternal alloantigens are still puzzling and pregnancy remains a fascinating phenomenon. Moreover, most studies focused on the maternal and fetal contribution to pregnancy success, and relatively little is known about the paternal involvement. In the current review, we address the contribution of paternal-derived factors to fetal-tolerance induction. First, we discuss data suggesting that in both humans and mice, the female body gets prepared for a pregnancy in every cycle, also in regard to male alloantigens delivered at coitus. Then, we provide an overview about factors present in seminal fluid and how these factors influence immune responses in the female reproductive tract. We further discuss ways of paternal alloantigen presentation and identify the immune modulatory properties of seminal fluid-derived factors with a special focus on Treg biology. Finally, we highlight the therapeutic potential of seminal fluid in different clinical applications.

The T helper type 17/regulatory T cell paradigm in pregnancy

“…At the onset of pregnancy, the semen also modulates the maternal immune response to promote a fetus‐friendly environment, so contributing to a healthy gestation . This immune‐modulatory stimulus will signal to the maternal immune response, activating a network of cells [human and murine macrophages and dendritic cells (DCs), as well as murine granulocytes, CD4 + CD25 + Treg cells, human lymphocytes and FOXP3 − Treg cells] and molecules (human TGF‐ β 1 and IL‐10, IL‐8 and IL‐2 receptor, among others) that will dampen the inflammatory immune response of the mother and allow the growth and development of the semi‐allogeneic fetus .…”

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

“…After entering the vagina, semen and spermatozoa induce innate and adaptive immune responses in the FRT. The result of this activated immunity is memory regulatory lymphocytes and memory effector lymphocytes formation, which is directed to paternal antigens (7)(8)(9)(10). Therefore, any alteration in seminal and spermatozoa antigenicity can result in disturbed immune response and consequently pregnancy aberration (7)(8)(9)(10).…”

A Review: Comparative Genomics and Physiology of Parity Mode Evolution in Amniotes

“…Under tenants gleaned from transplant medicine, the maternal immune system would illicit an attack response as early as insemination when maternal tissues are exposed to paternal alloantigens (Borziak et al, 2016;Schumacher & Zenclussen, 2015;Seavey & Mosmann, 2006).…”

“…Instead, maternal cells immunologically recognize them at this time without attack (Schumacher & Zenclussen, 2015;Seavey & Mosmann, 2006;Zenclussen et al, 2010). Treg expansion, a process with major influence on maternal-fetal immunotolerance in mammals, is proposed to be driven by several different factors found in seminal plasma (Baratelli et al, 2005;Clark, Fernandez, & Banwatt, 2008;Teles et al, 2013).…”