Cumulative exposure to paternal seminal fluid prior to conception and subsequent risk of preeclampsia

J Reprod Immunol. 2014 Mar:101-102:104-110. doi: 10.1016/j.jri.2013.07.006. Epub 2013 Aug 15.


A growing body of literature suggests that prior and prolonged exposure to paternal antigens in seminal fluid induces maternal tolerance to the allogeneic fetus, protecting it from rejection and facilitating successful implantation and placentation. In this case-control study of nulliparous women, we test the hypothesis that increased exposure to paternal seminal fluid via the vaginal or oral route will confer a reduced risk of preeclampsia. Preeclampsia cases (n=258) and normotensive controls (n=182) were selected from live births to Iowa women over the period August 2002 to April 2005. Disease status was verified by medical chart review. Seminal fluid exposure indexes incorporated information on type and frequency of sexual practices, contraceptive use, and ingestion practices prior to conception with the baby's father. Preeclampsia risk decreased significantly with increasing vaginal exposure to paternal semen (test for trend p<0.05). Women in the highest 10th percentile of vaginal exposure had a 70% reduced odds of preeclampsia relative to women in the lowest 25th percentile of exposure (aOR=0.3; 95% CI: 0.1-0.9). Oral seminal fluid exposure was not associated with a reduced risk of preeclampsia. These findings are congruent with the immune maladaptation hypothesis of preeclampsia causation and indicate that paternal antigen exposure via the vaginal mucosa may facilitate immune tolerance to paternal HLA. Thus, advising nulliparous women to decrease their use of barrier contraceptive methods and to increase vaginal sexual intercourse prior to conceiving may reduce their risk of preeclampsia.

Keywords: Epidemiology; Immunology; Paternity; Preeclampsia; Seminal fluid; Sperm.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Case-Control Studies
  • Coitus
  • Environmental Exposure / statistics & numerical data
  • Female
  • Humans
  • Immune Tolerance
  • Iowa
  • Isoantigens / immunology*
  • Male
  • Paternity
  • Pre-Eclampsia / epidemiology
  • Pre-Eclampsia / immunology*
  • Preconception Care
  • Pregnancy
  • Risk
  • Semen / immunology*
  • Sexual Behavior / statistics & numerical data
  • Young Adult


  • Isoantigens