Aldosterone deficiency adversely affects pregnancy outcome in mice
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Circulating aldosterone levels are increased in human pregnancy. Inadequately low aldosterone levels as present in preeclampsia, a life-threatening disease for both mother and child, are discussed to be involved in its pathogenesis or severity. Moreover, inactivating polymorphisms in the aldosterone synthase gene have been detected in preeclamptic women. Here, we used aldosterone synthase-deficient (AS−/−) mice to test whether the absence of aldosterone is sufficient to impair pregnancy or even to cause preeclampsia. AS−/− and AS+/+ females were mated with AS+/+ and AS−/− males, respectively, always generating AS+/− offspring. With maternal aldosterone deficiency in AS−/− mice, systolic blood pressure was low before and further reduced during pregnancy with no increase in proteinuria. Yet, AS−/− had smaller litters due to loss of fetuses as indicated by a high number of necrotic placentas with massive lymphocyte infiltrations at gestational day 18. Surviving fetuses and their placentas from AS−/− females were smaller. High-salt diet before and during pregnancy increased systolic blood pressure only before pregnancy in both genotypes and abolished the difference in blood pressure during late pregnancy. Litter size from AS−/− was slightly improved and the differences in placental and fetal weights between AS+/+ and AS−/− mothers disappeared. Overall, an increased placental efficiency was observed in both groups paralleled by a normalization of elevated HIF1α levels in the AS−/− placentas. Our results demonstrate that aldosterone deficiency has profound adverse effects on placental function. High dietary salt intake improved placental function. In this animal model, aldosterone deficiency did not cause preeclampsia.
KeywordsAldosterone Placenta Fetal growth Systolic blood pressure High-salt diet
We gratefully acknowledge the technical support by the Zurich Integrative Rodent Physiology (ZIRP) facility. We thank Charlotte Burger for expert technical help with tissue processing and slide scanning. Imaging was performed with equipment maintained by the Center for Microscopy and Image Analysis, University of Zurich. This study was supported by a collaborative project grant by the Zurich Center for Integrative Human Physiology (ZIHP) to J. Loffing and C.A. Wagner. The laboratories of J. Loffing and C.A. Wagner are also supported by independent project grants from the Swiss National Science Foundation (JL: 310030-122243; CAW: 31003A_138143/1) and by funds from the Swiss National Centre of Competence in Research “Kidney.CH”. M. Mohaupt was supported by the Swiss National Science Foundation by an independent project grant (3200030_135596/1) and also by funds from the Swiss National Centre of Competence in Research “Kidney.CH”.
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