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

Sarah A. Robertson, John J. Bromfield, Kelton P. Tremellen

Research output: Contribution to journalArticlepeer-review

91 Citations (Scopus)

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 (TGFβ), 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. TGFβ 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 TGFβ 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.

Original languageEnglish
Pages (from-to)253-265
Number of pages13
JournalJOURNAL OF REPRODUCTIVE IMMUNOLOGY
Volume59
Issue number2
DOIs
Publication statusPublished - Aug 2003
Externally publishedYes

Keywords

  • Leukocytes
  • Pre-eclampsia
  • Semen
  • Seminal plasma
  • Transforming growth factor-β

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