Theory of the etiology of human toxemia of pregnancy: fetal hyperinsulinemia as a compensatory response to decreased uterine blood flow.
Toxemia of pregnancy is a perplexing clinical problem that has defied accurate elucidation of its etiology because the disorder does not occur in undisturbed lower mammalian species that are currently used as animal models of reproductive physiology. We propose that toxemia of pregnancy occurs as the end stage human fetal-placental unit response to decreased maternal uterine blood flow, and that this fetal-placental unit response may be unique to the human species. The human fetus increases insulin secretion in response to progressive intrauterine asphyxia, which may result in decreased fetal-placental prostacyclin production (a vasodilator and inhibitor of platelet aggregation) and increased fetal-placental thromboxane A2 production (a vasoconstrictor). This could result in increased uteroplacental perfusion pressure, maternal hypertension, and increased maternal platelet aggregation. We also suggest that women who develop idiopathic toxemia of pregnancy are at increased risk for adult onset diabetes later on in life because they have a mild derangement in glucose-insulin homeostasis during their reproductive years that results in increased uterine vascular damage, that leads to decreased uterine blood flow, and ultimately the fetal hyperinsulinemia-prostaglandin pressor release mechanism. Therefore, prevention of toxemia may be possible by correction of mild derangements in glucose-insulin receptor homeostasis before conception occurs.
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D005260:Female; D005333:Fetus / Q000502:physiology*; D006801:Humans; D006946:Hyperinsulinism / Q000196:embryology* / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008431:Maternal-Fetal Exchange; D011225:Pre-Eclampsia / Q000209:etiology* / Q000503:physiopathology; D011247:Pregnancy; D014599:Uterus / Q000098:blood supply
D007328:Insulin