Obesity-associated non-oxidative genotoxic stress alters trophoblast turnover in human first-trimester placentas.

Placental growth is most rapid during the first trimester (FT) of pregnancy, making it vulnerable to metabolic and endocrine influences. Obesity, with its inflammatory and oxidative stress, can cause cellular damage. We hypothesized that maternal obesity increases DNA damage in the FT placenta, affecting DNA damage response and trophoblast turnover.

Effect of Omega-3 Supplementation in Pregnant Women with Obesity on Newborn Body Composition, Growth and Length of Gestation: A Randomized Controlled Pilot Study.

Maternal obesity, a state of chronic low-grade metabolic inflammation, is a growing health burden associated with offspring adiposity, abnormal fetal growth and prematurity, which are all linked to adverse offspring cardiometabolic health. Higher intake of anti-inflammatory omega-3 (n-3) polyunsaturated fatty acids (PUFA) in pregnancy has been associated with lower adiposity, higher birthweight and longer gestation. However, the effects of n-3 supplementation specifically in pregnant women with overweight and obesity (OWOB) have not been explored.

Longitudinal Assessment of Relationships Between Health Behaviors and IL-6 in Overweight and Obese Pregnancy.

Background: Inflammation is a common factor in adverse pregnancy outcomes (APOs). Behavioral factors influence inflammatory markers and APOs but rarely have been investigated simultaneously in pregnancy. Our purpose was to determine how diet, physical activity, and obesity are associated with interleukin (IL)-6 in early and late pregnancy.

Both glycaemic control and insulin dose during pregnancy in women with type 1 diabetes are associated with neonatal anthropometric measures and placental weight.

Background: To investigate longitudinal associations of maternal glucose/HbA and insulin dose with birthweight-related outcomes in women with type 1 diabetes.

Methods: We performed a cohort study including 473 pregnant women with type 1 diabetes with singleton pregnancies. We investigated maternal self-monitored blood glucose (SMBG, mmol/L), HbA (%, mmol/mol) and insulin dose (IU/kg/day) in the three trimesters as potential independent variables, while adjusting for potential confounders.

Longitudinal changes in glucose metabolism in women with gestational diabetes, from late pregnancy to the postpartum period.

Aims/hypothesis: This study aimed to determine, in women with gestational diabetes (GDM), the changes in insulin sensitivity (Matsuda Insulin Sensitivity Index; IS), insulin response and disposition index (DI) from late pregnancy (34-37 weeks gestation, T1), to early postpartum (1-5 days, T2) and late postpartum (6-12 weeks, T3). A secondary aim was to correlate the longitudinal changes in maternal lipids, adipokines, cytokines and weight in relation to the changes in IS, insulin response and DI.

Methods: IS, insulin response and DI were calculated at the three time points (T1, T2 and T3) using the results of a 75 g OGTT.

Diabesity-associated oxidative and inflammatory stress signalling in the early human placenta.

Early pregnancy is characterized by a series of complex and tightly regulated events to ultimately establish implantation and early placental development. One of the key events is the opening of the decidual spiral arteries into the intervillous space. It leads to a rise in oxygen tension in the intervillous space and the placenta and will induce transcriptional and translational changes of oxygen-sensitive molecules including antioxidants.

Effect of Maternal Obesity on Placental Lipid Metabolism.

Obese women, on average, give birth to babies with high fat mass. Placental lipid metabolism alters fetal lipid delivery, potentially moderating neonatal adiposity, yet how it is affected by maternal obesity is poorly understood. We hypothesized that fatty acid (FA) accumulation (esterification) is higher and FA β-oxidation (FAO) is lower in placentas from obese, compared with lean women.

Serotonin transporter protects the placental cells against apoptosis in caspase 3-independent pathway.

Serotonin (5-HT) and its specific transporter, SERT play important roles in pregnancy. Using placentas dissected from 18d gestational SERT-knock out (KO), peripheral 5-HT (TPH1)-KO, and wild-type (WT) mice, we explored the role of 5-HT and SERT in placental functions in detail. An abnormal thick band of fibrosis and necrosis under the giant cell layer in SERT-KO placentas appeared only moderately in TPH1-KO and minimally present in WT placentas.

Causal relationship between obesity-related traits and TLR4-driven responses at the maternal-fetal interface.

Aims/hypothesis: Obesity triggers complex inflammatory networks within the innate immune system. During pregnancy, the placenta amplifies the low-grade inflammation through activation of Toll-like receptor 4 (TLR4) signalling pathways. The purpose of this study was to investigate the impact of obesity on placental TLR4 expression and inflammatory signals.

Effect of ω-3 supplementation on placental lipid metabolism in overweight and obese women.

Background: The placentas of obese women accumulate lipids that may alter fetal lipid exposure. The long-chain omega-3 fatty acids (n–3 FAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) alter FA metabolism in hepatocytes, although their effect on the placenta is poorly understood.

Objective: We aimed to investigate whether n–3 supplementation during pregnancy affects lipid metabolism in the placentas of overweight and obese women at term.

Maternal fat, but not lean, mass is increased among overweight/obese women with excess gestational weight gain.

Background: Weight gain in pregnancy is an essential physiologic adaptation that supports growth and development of a fetus and is distributed among lean mass that includes total body water and fat mass gains. Although gestational weight gain provides a source of energy for the mother and fetus, excess gestational weight gain may underlie reported associations between parity and future metabolic disorders and is linked to postpartum weight retention and insulin resistance. Although weight gain often is proposed as a modifiable variable to mitigate adverse maternal and offspring health outcomes, our knowledge of specific maternal body composition changes with weight gain and the potential metabolic consequences is limited.

Endocrine and metabolic adaptations to pregnancy; impact of obesity.

Adaptations of maternal endocrine and metabolic homeostasis are central to successful pregnancy. They insure that an adequate and continuous supply of metabolic fuels is available for the growing fetus. Healthy pregnancy is classically described as a mild diabetogenic state with significant adjustments in both insulin production and sensitivity.

Dietary Omega-3 Fatty Acid Supplementation Reduces Inflammation in Obese Pregnant Women: A Randomized Double-Blind Controlled Clinical Trial.

Objective: Long-chain omega 3 fatty acids, eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) exert potent anti-inflammatory properties in humans. This study characterized the effects of omega-3 ω-3 fatty acids supplements (ω-3 FA) on the inflammatory status in the placenta and adipose tissue of overweight/obese pregnant women.

Study Design: A randomized, double-masked controlled trial was conducted in overweight/obese pregnant women that were randomly assigned to receive DHA plus EPA (2 g/day) or the equivalent of a placebo twice a day from week 10-16 to term.

Saturated fatty acids enhance TLR4 immune pathways in human trophoblasts.

Study Question: What are the effects of fatty acids on placental inflammatory cytokine with respect to toll-like receptor-4/nuclear factor-kappa B (TLR4/NF-kB)?

Summary Answer: Exogenous fatty acids induce a pro-inflammatory cytokine response in human placental cells in vitro via activation of TLR4 signaling pathways.

What Is Known Already: The placenta is exposed to changes in circulating maternal fatty acid concentrations throughout pregnancy. Fatty acids are master regulators of innate immune pathways through recruitment of toll-like receptors and activation of cytokine synthesis.

Are the metabolic changes of pregnancy reversible in the first year postpartum?

Aims/hypothesis: Maternal metabolic alterations are essential to achieve healthy pregnancy outcomes, but increasing maternal parity may be associated with long-term metabolic dysfunction risk. As existing data are limited by study design, our aim was to employ robust metabolic measures to determine whether or not physiological pregnancy alterations in maternal metabolic function persist at 1 year postpartum.

Methods: We evaluated 21 healthy women, of whom 11 had an interval pregnancy (IP) and assessment at preconception, during pregnancy and 1 year postpartum, and 10 had no IP and assessment at baseline and a 1 year interval.

Identification of early transcriptome signatures in placenta exposed to insulin and obesity.

Objective: The purpose of this study was to investigate the effects of insulin on human placental transcriptome and biological processes in first-trimester pregnancy.

Study Design: Maternal plasma and placenta villous tissue were obtained at the time of voluntary termination of pregnancy (7-12 weeks) from 17 lean (body mass index, 20.9±1.

Obesity-induced down-regulation of the mitochondrial translocator protein (TSPO) impairs placental steroid production.

Context: Low concentrations of estradiol and progesterone are hallmarks of adverse pregnancy outcomes as is maternal obesity. During pregnancy, placental cholesterol is the sole source of sex steroids. Cholesterol trafficking is the limiting step in sex steroid biosynthesis and is mainly mediated by the translocator protein (TSPO), present in the mitochondrial outer membrane.

Sex-specific effects of maternal anthropometrics on body composition at birth.

Objective: The purpose of this study was to assess whether maternal factors that are associated with fetal lean and fat mass differ between sexes.

Study Design: Secondary analysis of a prospective cohort that delivered by scheduled cesarean section from 2004-2013. Maternal blood was collected before surgery for metabolic parameters.

Patterns of adiponectin expression in term pregnancy: impact of obesity.

Context: Adiponectin (adpN) production is down-regulated in several situations associated with insulin resistance. The hypoadiponectinemia, which develops in late pregnancy, suggests a role of adpN in pregnancy-induced insulin resistance.

Objective: In obese pregnancy there is a decreased systemic adpN, which results from down-regulation of gene expression in adipose tissue.

Does the dawn phenomenon have clinical relevance in normal pregnancy?

Objective: The dawn phenomenon is a transient rise in blood glucose between 4 and 6 am that is attributed to the pulsatile release of pituitary growth hormone (GH). In pregnancy, GH is suppressed by placental GH. Hence, we hypothesize that there is no evidence for the dawn phenomenon in late pregnancy in healthy women.

Increased death of adipose cells, a path to release cell-free DNA into systemic circulation of obese women.

Remodeling of adipose tissue is required to support the expansion of adipose mass. In obesity, an increased death of adipocytes contributes to the accelerated cellular turnover. We have shown that obesity in pregnancy is associated with metabolic and immune alterations in the adipose tissue.

Molecular inflammation and adipose tissue matrix remodeling precede physiological adaptations to pregnancy.

Changes in adipose tissue metabolism are central to adaptation of whole body energy homeostasis to pregnancy. To gain insight into the molecular mechanisms supporting tissue remodeling, we have characterized the longitudinal changes of the adipose transcriptome in human pregnancy. Healthy nonobese women recruited pregravid were followed in early (8-12 wk) and in late (36-38 wk) pregnancy.