Seminal 'priming' for protection from pre-eclampsia-a unifying hypothesis.
Conventional belief holds that an immune response to ejaculate antigens should interfere with fertilisation and establishment of pregnancy. However, emerging evidence now supports the opposing view-that insemination acts to activate maternal immune mechanisms exerting a positive effect on reproductive events. In a response well documented in rodents, semen triggers an influx of antigen-presenting cells into the female reproductive tract which process and present paternal ejaculate antigens to elicit activation of lymphocytes in the adaptive immune compartment. Transforming growth factor beta (TGFbeta), a cytokine present in abundance in seminal plasma, initiates this inflammatory response by stimulating the synthesis of pro-inflammatory cytokines and chemokines in uterine tissues. Lymphocyte activation is evident in lymph nodes draining the uterus and leads to hypo-responsiveness in T-cells reactive with paternal alloantigens. TGFbeta has potent immune-deviating effects and is likely to be the key agent in skewing the immune response against a Type-1 bias. Prior exposure to semen in the context of TGFbeta can be shown to be associated with enhanced fetal-placental development late in gestation. In this paper, we review the experimental basis for these claims and propose the hypothesis that, in women, the partner-specific protective effect of insemination in pre-eclampsia might be explained by induction of immunological hypo-responsiveness conferring tolerance to histocompatibility antigens present in the ejaculate and shared by the conceptus.
Robertson
Sarah A
SA
Department of Obstetrics and Gynaecology, Adelaide University, SA 5005 Adelaide, Australia. sarah.robertson@adelaide.edu.au
Bromfield
John J
JJ
Tremellen
Kelton P
KP
D000818:Animals; D017951:Antigen Presentation; D016207:Cytokines / Q000378:metabolism; D010064:Embryo Implantation; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D018836:Inflammation Mediators / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008431:Maternal-Fetal Exchange; D018448:Models, Immunological; D011225:Pre-Eclampsia / Q000276:immunology*; D011247:Pregnancy; D012661:Semen / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000276:immunology
D016207:Cytokines; D018836:Inflammation Mediators; D016212:Transforming Growth Factor beta