Review: The feto-placental unit, pregnancy pathology and impact on long term maternal health
ABSTRACT Pregnancy induces a number of alterations to maternal physiology to accommodate the increased demands made by the developing fetus and placenta. These alterations appear at least in part to be driven by products derived from the feto-placental unit, including microchimeric cells, as well as placental exosomes and microparticles, inducing changes to maternal physiology both during pregnancy and beyond. Further, increasing evidence suggests that some of these alterations are dependent on the sex of the fetus. Pre-eclampsia and asthma represent two common pregnancy complications that have provided valuable insight into how the feto-placental unit influences maternal physiology in a sex-specific manner. Pregnancy-induced alterations in maternal physiology may expose pre-existing subclinical pathologies and provide insight into future maternal health and disease. While most pregnancy-induced alterations to the maternal system are reversed following delivery, some can persist after parturition leading to cardiovascular, metabolic and autoimmune disease and increased risk of early mortality.
- SourceAvailable from: Chike Magnus Nzerue
- "The differences in risk among ethnic groups suggest a strong role for genetic factors in the pathogenesis of preeclampsia. Most theories on the etiology of preeclampsia suggest that the disease is a cascade triggered by combination of abnormal maternal inflammatory response, endothelial cell activation/damage with deranged hemodynamic milieu, and deranged immunity [7–12]. The precise trigger that unifies the deranged vascular, immune and inflammatory responses remains to be elucidated. "
Article: Preeclampsia 2012[Show abstract] [Hide abstract]
ABSTRACT: Preeclampsia is a common complication of pregnancy associated with high maternal morbidity and mortality and intrauterine fetal growth restriction. There is extensive evidence that the reduction of uteroplacental blood flow in this syndrome results from the toxic combination of hypoxia, imbalance of angiogenic and antiangiogenic factors, inflammation, and deranged immunity. Women treated for preeclampsia also have an increased risk for cardiovascular and renal disease. At present it is unclear if the increased cardiovascular and renal disease risks are due to residual and or progressive effects of endothelial damage from the preeclampsia or from shared risk factors between preeclampsia and cardiac disease. Moreover, it appears that endothelin-1 signaling may play a central role in the hypertension associated with preeclampsia. In this paper, we discuss emerging data on the pathogenesis of preeclampsia and review therapeutic options.Journal of pregnancy 07/2012; 2012:586578. DOI:10.1155/2012/586578
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ABSTRACT: OBJECTIVES: To evaluate the effect of preeclampsia (PE) and gestational hypertension (GH) on subsequent hypothyroidism. Recent studies suggest that women with PE have increased risk for reduced thyroid function, but the association between PE and GH with overt hypothyroidism has not been examined. STUDY DESIGN: Two prospective population-based cohort studies, the Northern Finland Birth Cohorts 1966 and 1986, followed women who had PE (N=955), GH (N=1449) or were normotensive (N=13531) during pregnancy. Finnish national registers were used to confirm subsequent hypothyroidism. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) estimated hypothyroidism risk when comparing women with PE or GH with normotensive women. MAIN OUTCOME MEASURES: Primary hypothyroidism during follow-up of 20-40 years. RESULTS: The subsequent prevalence of hypothyroidism was higher among women with PE (4.0%) and GH (4.5%) compared with normotensive women (3.5%), but the risk increase was not significant (aHR for PE 1.13, 95%CI 0.80-1.59 and aHR for GH 1.11, 95%CI 0.85-1.45). Subgroup analysis among nulliparous women revealed a significant association between late PE and subsequent hypothyroidism (aHR 1.82, 95%CI 1.04-3.19). Early or recurrent PE were not associated with hypothyroidism (aHR 0.93, 95%CI 0.46-1.81 and aHR 1.35, 95%CI 0.63-2.88, respectively). CONCLUSIONS: Overall, PE or GH during pregnancy was not significantly associated with subsequent hypothyroidism in Finnish women after 20-40 years of follow-up. However, late PE in nulliparous women was associated with a 1.8-fold increased risk of subsequent hypothyroidism, a finding that merits further study in other populations.01/2013; 3(1):21-27. DOI:10.1016/j.preghy.2012.09.001
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ABSTRACT: Sex differences occur in most non-communicable diseases, including metabolic diseases, hypertension, cardiovascular disease, psychiatric and neurological disorders and cancer. In many cases, the pathogenesis of these diseases begins early in development. The observed differences between the sexes may result from genetic and hormonal differences and from differences in responses to and interactions with environmental factors, including infection, diet, drugs and stress. The placenta plays a key role in fetal growth and development and, as such, affects the fetal programming underlying subsequent adult health and accounts, in part for the developmental origin of health and disease (DOHaD). There is accumulating evidence to demonstrate the sex-specific relationships between diverse environmental influences on placental functions and the risk of disease later in life. As one of the few tissues easily collectable in humans, this organ may therefore be seen as an ideal system for studying how male and female placenta sense nutritional and other stresses, such as endocrine disruptors. Sex-specific regulatory pathways controlling sexually dimorphic characteristics in the various organs and the consequences of lifelong differences in sex hormone expression largely account for such responses. However, sex-specific changes in epigenetic marks are generated early after fertilization, thus before adrenal and gonad differentiation in the absence of sex hormones and in response to environmental conditions. Given the abundance of X-linked genes involved in placentogenesis, and the early unequal gene expression by the sex chromosomes between males and females, the role of X- and Y-chromosome-linked genes, and especially those involved in the peculiar placenta-specific epigenetics processes, giving rise to the unusual placenta epigenetic landscapes deserve particular attention. However, even with recent developments in this field, we still know little about the mechanisms underlying the early sex-specific epigenetic marks resulting in sex-biased gene expression of pathways and networks. As a critical messenger between the maternal environment and the fetus, the placenta may play a key role not only in buffering environmental effects transmitted by the mother but also in expressing and modulating effects due to preconceptional exposure of both the mother and the father to stressful conditions.03/2013; 4(1):5. DOI:10.1186/2042-6410-4-5