Seminal 'priming' for protection from pre-eclampsia-a unifying hypothesis

J Reprod Immunol. 2003 Aug;59(2):253-65. doi: 10.1016/s0165-0378(03)00052-4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigen Presentation
  • Cytokines / metabolism
  • Embryo Implantation
  • Female
  • Humans
  • Immune Tolerance*
  • Inflammation Mediators / chemistry
  • Inflammation Mediators / metabolism*
  • Male
  • Maternal-Fetal Exchange
  • Models, Immunological
  • Pre-Eclampsia / immunology*
  • Pregnancy
  • Semen / immunology*
  • Transforming Growth Factor beta / chemistry
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Trophoblasts / immunology

Substances

  • Cytokines
  • Inflammation Mediators
  • Transforming Growth Factor beta