Preeclampsia—the immune maladaptation hypothesis
- 1.A more prolonged period of sperm exposure provides a partial protection against early-onset preeclampsia. All women with changing partners are strongly advised to use condoms to prevent sexually transmitted diseases. However, a certain period of sperm exposure within a stable relation, when pregnancy is aimed for, is associated with a partial protection against preeclampsia.14,15
- 2.According to the primipaternity concept, a multiparous woman with a new partner should be approached as being a primigravid women.14,15All primigravid pregnant women and multiparous women with a new partner should be asked about the length of their sexual relationship with the father of the pregnancy.16,17
- 3.Artificial donor insemination, oocyte donation, and embryo donation are associated with an increased risk of developing pregnancy-induced hypertensive disorders.16,17
|Major advances in immunology of reproduction|
|Redman and Sargent,|
|Anthropological mysteries on human “extravagant” sexuality disconnected with reproduction (Diamond, 1997)|
|Evolutionary adaptation of human reproduction and “extravagant” sexuality|
The innate immune system: the role of natural killer cells
- Nakabayashi Y.
- Nakashima A.
- Yoshino O.
- et al.
The paramount immunologic role of semen for induction of paternal antigen-specific regulatory T cells
- Shima T.
- Inada K.
- Nakashima A.
- et al.
The involvement of the balance of regulatory T cells and cytotoxic T cells in preeclampsia
|Early onset||Late onset|
|Impairment of paternal antigens-specific tolerance|
|First pregnancy in primigravida||Yes||Weak||No|
|First pregnancy in multipara cases with new partner||Yes||Weak||No|
|Impairment of seminal plasma priming|
|Use of condoms||Yes||Weak||No|
|Artificial insemination by donor||Yes||Weak||No|
|Complete allografted fetus|
What is the interaction between immunologic alterations and the placental metabolic syndrome in preeclampsia?
What about prevention of preeclampsia
- https://www.ajog.org/cms/asset/afa71828-57c2-4888-a447-5b40ee057e79/mmc1.mp4Loading ...
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- Pre-eclampsia: pathophysiology and clinical implications.BMJ. 2019; 366: I2381
- Preeclampsia, biomarkers, syncytiotrophoblast stress, and placental capacity.Am J Obstet Gynecol. 2015; 213: S9.e1-S9.e11
- Placental stress and pre-eclampsia: a revised view.Placenta. 2009; 30: S38-S42
- Preeclampsia: updates in pathogenesis, definitions, and guidelines.Clin J Am Soc Nephrol. 2016; 11: 1102-1113
- Preeclampsia: pathophysiology, challenges, and perspectives.Circ Res. 2019; 124: 1094-1112
- Circulating angiogenic factors and the risk of preeclampsia.N Engl J Med. 2004; 350: 672-683
- The placenta and preeclampsia: villain or victim?.Am J Obstet Gynecol. 2021; ([Epub ahead of print])
- Predictive value of the sFlt-1:PlGF ratio in women with suspected preeclampsia.N Engl J Med. 2016; 374: 13-22
- Short-term prediction of adverse outcomes using the sFlt-1 (soluble fms-like tyrosine kinase 1)/PlGF (placental growth factor) ratio in Asian women with suspected preeclampsia.Hypertension. 2019; 74: 164-172
- Decidualization resistance in the origin of preeclampsia.Am J Obstet Gynecol. 2020; ([Epub ahead of print])
- Defective decidualization during and after severe preeclampsia reveals a possible maternal contribution to the etiology.Proc Natl Acad Sci U S A. 2017; 114: E8468-E8477
- The interval between pregnancies and the risk of preeclampsia.N Engl J Med. 2002; 346: 33-38
- Inadequate tolerance induction may induce pre-eclampsia.J Reprod Immunol. 2007; 76: 30-39
- Association of pregnancy-induced hypertension with duration of sexual cohabitation before conception.Lancet. 1994; 344: 973-975
- Change in paternity: a risk factor for preeclampsia in multiparous women?.J Reprod Immunol. 1999; 45: 81-88
- Revisiting the epidemiological standard of preeclampsia: primigravidity or primipaternity?.Eur J Obstet Gynecol Reprod Biol. 1999; 84: 37-41
- Historical evolution of ideas on eclampsia/preeclampsia: a proposed optimistic view of preeclampsia.J Reprod Immunol. 2017; 123: 72-77
- Primipaternities and human birthweights.J Reprod Immunol. 2021; 147: 103365
- Learning from experience: cellular and molecular bases for improved outcome in subsequent pregnancies.Am J Obstet Gynecol. 2019; 221: 183-193
- High incidence of early onset preeclampsia is probably the rule and not the exception worldwide. 20th anniversary of the reunion workshop. A summary.J Reprod Immunol. 2019; 133: 30-36
- Evolutionary adaptations to pre-eclampsia/eclampsia in humans: low fecundability rate, loss of oestrus, prohibitions of incest and systematic polyandry.Am J Reprod Immunol. 2002; 47: 104-111
- über Albuminurie in der Schwangerschaft. Ein Beitrag zur Physiologie der Schwangerschaft.Berl Klin Wchschr. 1902; 3: 513-516
- Isoagglutination in the newborn infants and their mother: a possible relationship between interagglutination and the toxemias of pregnancy.John Hopkins Hosp Bull. 1923; 34: 51-54
- Some immunological and endocrinological problems raised by the evolution of viviparity in vertebrates.in: Evolution 7. Society for Experimental Biology, Academic Press, New York1953: 320-338
- Can murine uterine natural killer cells give insights into the pathogenesis of preeclampsia?.J Soc Gynecol Investig. 2000; 7: 12-20
- Natural killer cells and pregnancy.Nat Rev Immunol. 2002; 2: 656-663
- Combinations of maternal KIR and fetal HLA-C genes influence the risk of preeclampsia and reproductive success.J Exp Med. 2004; 200: 957-965
- Trained memory of human uterine NK cells enhances their function in subsequent pregnancies.Immunity. 2018; 48: 951-962.e5
- Spiral arterial remodeling is not essential for normal blood pressure regulation in pregnant mice.Hypertension. 2010; 55: 729-737
- Impairment of the accumulation of decidual T cells, NK cells, and monocytes, and the poor vascular remodeling of spiral arteries, were observed in oocyte donation cases, regardless of the presence or absence of preeclampsia.J Reprod Immunol. 2016; 114: 65-74
- Regulatory T cells mediate maternal tolerance to the fetus.Nat Immunol. 2004; 5: 266-271
- Proportion of peripheral blood and decidual CD4(+) CD25(bright) regulatory T cells in pre-eclampsia.Clin Exp Immunol. 2007; 149: 139-145
- Recurrent pregnancy loss.Nat Rev Dis Primers. 2020; 6: 98
- Seminal fluid drives expansion of the CD4+CD25+ T regulatory cell pool and induces tolerance to paternal alloantigens in mice.Biol Reprod. 2009; 80: 1036-1045
- Uterine CD11c+ cells induce the development of paternal antigen-specific Tregs via seminal plasma priming.J Reprod Immunol. 2020; 141: 103165
- Pregnancy imprints regulatory memory that sustains anergy to fetal antigen.Nature. 2012; 490: 102-106
- Clonally expanded decidual effector regulatory T cells increase in late gestation of normal pregnancy, but not in preeclampsia, in humans.Front Immunol. 2018; 9: 1934
- Uterine DCs are crucial for decidua formation during embryo implantation in mice.J Clin Invest. 2008; 118: 3954-3965
- Dynamic changes in the phenotype of dendritic cells in the uterus and uterine draining lymph nodes after coitus.Front Immunol. 2020; 11: 557720
- Paternal antigen-specific proliferating regulatory T cells are increased in uterine-draining lymph nodes just before implantation and in pregnant uterus just after implantation by seminal plasma-priming in allogeneic mouse pregnancy.J Reprod Immunol. 2015; 108: 72-82
- Seminal transforming growth factor beta1 stimulates granulocyte-macrophage colony-stimulating factor production and inflammatory cell recruitment in the murine uterus.Biol Reprod. 1998; 58: 1217-1225
- Transforming growth factor beta--a mediator of immune deviation in seminal plasma.J Reprod Immunol. 2002; 57: 109-128
- CD206+ M2-like macrophages are essential for successful implantation.Front Immunol. 2020; 11: 557184
- Therapeutic potential of regulatory T cells in preeclampsia-opportunities and challenges.Front Immunol. 2019; 10: 478
- Recurrent miscarriages and the association with regulatory T cells; a systematic review.J Reprod Immunol. 2020; 139: 103105
- Analysis of TCR repertoire and PD-1 expression in decidual and peripheral CD8 + T cells reveals distinct immune mechanisms in miscarriage and preeclampsia.Front Immunol. 2020; 11: 1082
- CD8 + T cell functional exhaustion overrides pregnancy-induced fetal antigen alloimmunization.Cell Rep. 2020; 31: 107784
- Regulatory T and T helper 17 cells: their roles in preeclampsia.J Cell Physiol. 2018; 233: 6561-6573
- Preeclampsia is associated with increased cytotoxic T-cell capacity to paternal antigens.Am J Obstet Gynecol. 2010; 203: 496.e1-496.e6
- Preeclampsia: a couple’s disease with maternal and fetal manifestations.Curr Pharm Des. 2005; 11: 699-710
- The etiology of preeclampsia: the role of the father.J Reprod Immunol. 2011; 89: 126-132
- Regulatory T cells are necessary for implantation and maintenance of early pregnancy but not late pregnancy in allogeneic mice.J Reprod Immunol. 2010; 85: 121-129
- Regulatory T cells play a role in a subset of idiopathic preterm labor/birth and adverse neonatal outcomes.Cell Rep. 2020; 32: 107874
- Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy.Am J Reprod Immunol. 2010; 63: 601-610
- Cellular immune responses in the pathophysiology of preeclampsia.J Leukoc Biol. 2021; ([Epub ahead of print])
- Preeclampsia: an excessive maternal inflammatory response to pregnancy.Am J Obstet Gynecol. 1999; 180: 499-506
- Manifestations of metabolic syndrome after hypertensive pregnancy.Hypertension. 2004; 43: 825-831
- Metabolic syndrome in pregnancy and risk for adverse pregnancy outcomes: a prospective cohort of nulliparous women.PLoS Med. 2018; 15e1002710
- Endothelial dysfunction and metabolic syndrome in preeclampsia: an alternative viewpoint.J Reprod Immunol. 2015; 108: 42-47
- P-type inositol phosphoglycans in serum and amniotic fluid in active pre-eclampsia.J Reprod Immunol. 2006; 69: 165-179
- Endometrial secretions: creating a stimulatory microenvironment within the human early placenta and implications for the aetiopathogenesis of preeclampsia.J Reprod Immunol. 2011; 89: 118-125
- Exploring strengths and limits of urinary D-chiro inositol phosphoglycans (IPG-P) as a screening test for preeclampsia: a systematic review and meta-analysis.J Reprod Immunol. 2019; 134: 21-27
- A top priority in pre-eclampsia research: development of a reliable and inexpensive urinary screening test.Lancet Glob Health. 2019; 7: e1312-e1313
- Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia.N Engl J Med. 2017; 377: 613-622
- Maternal obesity and the risk of early-onset and late-onset hypertensive disorders of pregnancy.Obstet Gynecol. 2020; 136: 118-127
- Increased BMI has a linear association with late-onset preeclampsia: a population-based study.PLoS One. 2019; 14e0223888
- Gestational weight gain and rate of late-onset preeclampsia: a retrospective analysis on 57 000 singleton pregnancies in Reunion Island.BMJ Open. 2020; 10: e036549
- The urgent need to optimize gestational weight in overweight/obese women to lower maternal- fetal moribidities: a retrospective analysis on 59,000 singleton term pregnancies.ARCH Women Health Care. 2020; 3: 1-9
- Risk factors for early and late onset preeclampsia in women without pathological history: confirmation of the paramount effect of excessive maternal pre-pregnancy corpulence on risk for late onset preeclampsia.Integr Gyn Obstet J. 2020; 3: 1-7
- The animal with the weirdest sex life.in: Diamond J, ed. Why is sex fun? The evolution of human sexuality. Basic Books, New York, NY1997: 1-13
- Wrong time for love.in: Diamond J, ed. Why is sex fun? The evolution of human sexuality. Basic Books, New York, NY1997: 63-88
The authors report no conflict of interest.
This study did not receive any financial support.
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