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      Pregnancy, parturition and preeclampsia in women of African ancestry

      review-article
      , MBChB, MMed (Obs&Gyn) a , , PhD b , , MBChB, MMed (Obs&Gyn), PhD a , , MA, MBBS, MD, DTM&H, FRCP c , d , , MD, PhD c , , MBChB, MMed (Obs&Gyn), PhD a , , MA, MB, BChir, MD, MRCP, MRCPath b ,
      American Journal of Obstetrics and Gynecology
      Elsevier
      evolutionary selective pressure, great obstetric syndromes, length of gestation, obstetric dilemma

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          Abstract

          Maternal and associated neonatal mortality rates in sub-Saharan Africa remain unacceptably high. In Mulago Hospital (Kampala, Uganda), 2 major causes of maternal death are preeclampsia and obstructed labor and their complications, conditions occurring at the extremes of the birthweight spectrum, a situation encapsulated as the obstetric dilemma. We have questioned whether the prevalence of these disorders occurs more frequently in indigenous African women and those with African ancestry elsewhere in the world by reviewing available literature. We conclude that these women are at greater risk of preeclampsia than other racial groups. At least part of this susceptibility seems independent of socioeconomic status and likely is due to biological or genetic factors. Evidence for a genetic contribution to preeclampsia is discussed. We go on to propose that the obstetric dilemma in humans is responsible for this situation and discuss how parturition and birthweight are subject to stabilizing selection. Other data we present also suggest that there are particularly strong evolutionary selective pressures operating during pregnancy and delivery in Africans. There is much greater genetic diversity and less linkage disequilibrium in Africa, and the genes responsible for regulating birthweight and placentation may therefore be easier to define than in non-African cohorts. Inclusion of African women into research on preeclampsia is an essential component in tackling this major disparity of maternal health.

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          Most cited references107

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          Combinations of Maternal KIR and Fetal HLA-C Genes Influence the Risk of Preeclampsia and Reproductive Success

          Preeclampsia is a serious complication of pregnancy in which the fetus receives an inadequate supply of blood due to failure of trophoblast invasion. There is evidence that the condition has an immunological basis. The only known polymorphic histocompatibility antigens on the fetal trophoblast are HLA-C molecules. We tested the idea that recognition of these molecules by killer immunoglobulin receptors (KIRs) on maternal decidual NK cells is a key factor in the development of preeclampsia. Striking differences were observed when these polymorphic ligand: receptor pairs were considered in combination. Mothers lacking most or all activating KIR (AA genotype) when the fetus possessed HLA-C belonging to the HLA-C2 group were at a greatly increased risk of preeclampsia. This was true even if the mother herself also had HLA-C2, indicating that neither nonself nor missing-self discrimination was operative. Thus, this interaction between maternal KIR and trophoblast appears not to have an immune function, but instead plays a physiological role related to placental development. Different human populations have a reciprocal relationship between AA frequency and HLA-C2 frequency, suggesting selection against this combination. In light of our findings, reproductive success may have been a factor in the evolution and maintenance of human HLA-C and KIR polymorphisms.
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            Natural killer cells and pregnancy.

            The fetus is considered to be an allograft that, paradoxically, survives pregnancy despite the laws of classical transplantation immunology. There is no direct contact of the mother with the embryo, only with the extraembryonic placenta as it implants in the uterus. No convincing evidence of uterine maternal T-cell recognition of placental trophoblast cells has been found, but instead, there might be maternal allorecognition mediated by uterine natural killer cells that recognize unusual fetal trophoblast MHC ligands.
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              Variable NK cell receptors and their MHC class I ligands in immunity, reproduction and human evolution.

              Natural killer (NK) cells have roles in immunity and reproduction that are controlled by variable receptors that recognize MHC class I molecules. The variable NK cell receptors found in humans are specific to simian primates, in which they have progressively co-evolved with MHC class I molecules. The emergence of the MHC-C gene in hominids drove the evolution of a system of NK cell receptors for MHC-C molecules that is most elaborate in chimpanzees. By contrast, the human system of MHC-C receptors seems to have been subject to different selection pressures that have acted in competition on the immunological and reproductive functions of MHC class I molecules. We suggest that this compromise facilitated the development of the bigger brains that enabled archaic and modern humans to migrate out of Africa and populate other continents.
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                Author and article information

                Contributors
                Journal
                Am J Obstet Gynecol
                Am. J. Obstet. Gynecol
                American Journal of Obstetrics and Gynecology
                Elsevier
                0002-9378
                1097-6868
                1 June 2014
                June 2014
                : 210
                : 6
                : 510-520.e1
                Affiliations
                [a ]Department of Obstetrics and Gynaecology, Makerere University and Mulago Hospital, Kampala, Uganda
                [b ]Department of Pathology and Centre for Trophoblast Research, University of Cambridge, Cambridge, United Kingdom
                [c ]Medical Research Council/Uganda Virus Research Institute Uganda Research Unit on AIDS, Entebbe, Uganda
                [d ]London School of Hygiene and Tropical Medicine, London, United Kingdom
                Author notes
                []Reprints: Ashley Moffett, MA, MB, BChir, MD, MRCP, MRCPath, Department of Pathology and Centre for Trophoblast Research, University of Cambridge, Tennis Court Rd., Cambridge CB2 1QP, United Kingdom. am485@ 123456cam.ac.uk
                Article
                S0002-9378(13)01989-3
                10.1016/j.ajog.2013.10.879
                4046649
                24184340
                a53978d6-e652-411c-a21a-c59f88055bfc
                © 2014 Mosby, Inc. All rights reserved.
                History
                : 11 September 2013
                : 22 October 2013
                : 28 October 2013
                Categories
                Expert Review
                Obstetrics

                Obstetrics & Gynecology
                evolutionary selective pressure,great obstetric syndromes,length of gestation,obstetric dilemma

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