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Maternal high-fat diet disturbs uteroplacental hemodynamics and increases the frequency of stillbirth in a nonhuman primate model of excess nutrition.

ABSTRACT: Prepregnancy maternal obesity confers an increased risk of stillbirth, but the mechanisms are unknown. Maternal obesity is associated with placental inflammation. We considered that maternal diet may predispose to the increased risk of placental inflammation and stillbirth. We hypothesized that a chronic high-fat diet (HFD) is associated with abnormal uteroplacental circulation and placental inflammation. Here we used a nonhuman primate model to determine the effect of chronic HFD on the uterine and placental hemodynamics, placental histology, and inflammation in a prospective, observational study of 24 Japanese macaques. Overall, there was a statistically significant (38-56%) reduction in uterine volume blood flow from HFD animals, whether they were lean or obese. Consumption of a HFD, independent of obesity, increased placental inflammatory cytokines and the expression of Toll-like receptor 4. We show that HFD consumption by obese mothers with hyperinsulinemia also reduced volume blood flow on the fetal side of the placenta and significantly increased the frequency of both placental infarctions and stillbirth. These results suggest that a HFD, independent of obesity, decreases uterine volume blood flow. Maternal obesity and insulin resistance further exacerbates the placental dysfunction and results in an increased frequency of stillbirth.

SUBMITTER: Frias AE

PROVIDER: S-EPMC3100625 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Maternal high-fat diet disturbs uteroplacental hemodynamics and increases the frequency of stillbirth in a nonhuman primate model of excess nutrition.

Frias Antonio E AE Morgan Terry K TK Evans Anne E AE Rasanen Juha J Oh Karen Y KY Thornburg Kent L KL Grove Kevin L KL

Endocrinology 20110329 6

Prepregnancy maternal obesity confers an increased risk of stillbirth, but the mechanisms are unknown. Maternal obesity is associated with placental inflammation. We considered that maternal diet may predispose to the increased risk of placental inflammation and stillbirth. We hypothesized that a chronic high-fat diet (HFD) is associated with abnormal uteroplacental circulation and placental inflammation. Here we used a nonhuman primate model to determine the effect of chronic HFD on the uterine ...[more]

PMID: 21447636

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Project description:Parthenogenesis is the biological phenomenon by which embryonic development is initiated without male contribution. Whereas parthenogenesis is a common mode of reproduction in lower organisms, the mammalian parthenote fails to produce a successful pregnancy. We herein describe in vitro parthenogenetic development of monkey (Macaca fascicularis) eggs to the blastocyst stage, and their use to create a pluripotent line of stem cells. These monkey stem cells (Cyno-1 cells) are positive for telomerase activity and are immunoreactive for alkaline phosphatase, octamer-binding transcription factor 4 (Oct-4), stage-specific embryonic antigen 4 (SSEA-4), tumor rejection antigen 1-60 (TRA 1-60), and tumor rejection antigen 1-81 (TRA 1-81) (traditional markers of human embryonic stem cells). They have a normal chromosome karyotype (40 + 2) and can be maintained in vitro in an undifferentiated state for extended periods of time. Cyno-1 cells can be differentiated in vitro into dopaminergic and serotonergic neurons, contractile cardiomyocyte-like cells, smooth muscle, ciliated epithelia, and adipocytes. When Cyno-1 cells were injected into severe combined immunodeficient mice, teratomas with derivatives from all three embryonic germ layers were obtained. When grown on fibronectin/laminin-coated plates and in neural progenitor medium, Cyno-1 cells assume a neural precursor phenotype (immunoreactive for nestin). However, these cells remain proliferative and express no functional ion channels. When transferred to differentiation conditions, the nestin-positive precursors assume neuronal and epithelial morphologies. Over time, these cells acquire electrophysiological characteristics of functional neurons (appearance of tetrodotoxin-sensitive, voltage-dependent sodium channels). These results suggest that stem cells derived from the parthenogenetically activated nonhuman primate egg provide a potential source for autologous cell therapy in the female and bypass the need for creating a competent embryo.

Dataset Information

Maternal high-fat diet disturbs uteroplacental hemodynamics and increases the frequency of stillbirth in a nonhuman primate model of excess nutrition.

Publications

Maternal high-fat diet disturbs uteroplacental hemodynamics and increases the frequency of stillbirth in a nonhuman primate model of excess nutrition.

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