Perrie O'Tierney-Ginn

Influence of high fat diet and resveratrol supplementation on placental fatty acid uptake in the Japanese macaque

INTRODUCTION Adequate maternal supply and placental delivery of long chain polyunsaturated fatty acids (LCPUFA) is essential for normal fetal development. In humans, maternal obesity alters placental FA uptake, though the impact of diet remains uncertain. The fatty fetal liver observed in offspring of Japanese macaques fed a high fat diet (HFD) was prevented with resveratrol supplementation during pregnancy. We sought to determine the effect of HFD and resveratrol, a supplement with insulin-sensitizing properties, on placental LCPUFA uptake in this model. METHODS J. macaques were fed control chow (15% fat, n = 5), HFD (35% fat, n = 10) or HFD containing 0.37% resveratrol (n = 5) prior to- and throughout pregnancy. At ∼ 130 d gestation (term = 173 d), placentas were collected by caesarean section. Fatty acid uptake studies using (14)C-labeled oleic acid, arachidonic acid (AA) and docosahexanoic acid (DHA) were performed in placental explants. RESULTS Resveratrol supplementation increased placental uptake of DHA (P < 0.05), while HFD alone had no measurable effect. Resveratrol increased AMP-activated protein kinase activity and mRNA expression of the fatty acid transporters FATP-4, CD36 and FABPpm (P < 0.05). Placental DHA content was decreased in HFD dams; resveratrol had no effect on tissue fatty acid profiles. DISCUSSION Maternal HFD did not significantly affect placental LCPUFA uptake. Furthermore, resveratrol stimulated placental DHA uptake capacity, AMPK activation and transporter expression. Placental handling of DHA is particularly sensitive to the dramatic alterations in the maternal metabolic phenotype and placental AMPK activity associated with resveratrol supplementation.

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. We assessed acylcarnitine profiles (lipid oxidation intermediates) in mother-baby-placenta triads, in addition to lipid content, and messenger RNA (mRNA)/protein expression of key regulators of FA metabolism pathways in placentas of lean and obese women with normal glucose tolerance recruited at scheduled term Cesarean delivery. In isolated trophoblasts, we measured [3H]-palmitate metabolism. Placentas of obese women had 17.5% (95% confidence interval: 6.1, 28.7%) more lipid than placentas of lean women, and higher mRNA and protein expression of FA esterification regulators (e.g., peroxisome proliferator-activated receptor γ, acetyl-CoA carboxylase, steroyl-CoA desaturase 1, and diacylglycerol O-acyltransferase-1). [3H]-palmitate esterification rates were increased in trophoblasts from obese compared with lean women. Placentas of obese women had fewer mitochondria and a lower concentration of acylcarnitines, suggesting a decrease in mitochondrial FAO capacity. Conversely, peroxisomal FAO was greater in placentas of obese women. Altogether, these changes in placental lipid metabolism may serve to limit the amount of maternal lipid transferred to the fetus, restraining excess fetal adiposity in this population of glucose-tolerant women.

Placental Growth Response to Maternal Insulin in Early Pregnancy

CONTEXT The sensitivity of the placenta to maternal insulin remains controversial. Early pregnancy may be a time of increased placental sensitivity to maternal insulin because insulin receptors are abundant on the syncytiotrophoblast in the first trimester but are far fewer at term. HYPOTHESIS Maternal insulin secretory response in early, but not late, pregnancy is positively associated with placental growth. DESIGN This is a secondary analysis of a cohort of women (n = 40) recruited before pregnancy. OUTCOME MEASURES An iv glucose tolerance test was administered before pregnancy and in early (12-14 weeks) and late (34-36 weeks) pregnancy. Placental volume throughout gestation (in a subset of women via 3-dimensional ultrasound) and weight at birth were recorded. RESULTS Total insulin secretory response in early pregnancy was positively associated with placental volume in early pregnancy (R = 0.79, P = 0.04) and placental weight at term (R = 0.42, P = 0.007). Insulin secretory response before and in late pregnancy was not significantly associated with placental growth. Although neonatal fat mass was strongly correlated with placental weight at term (R = 0.449, P = 0.0003), maternal insulin secretory response was related to neonatal fat mass only at birth in male offspring (R = 0.59, P = 0.008). CONCLUSIONS Maternal insulin secretory response in early pregnancy was strongly related to placental weight at birth. Thus, in early pregnancy, increased maternal insulin response as seen in obesity and gestational diabetes mellitus may be a key influence on placental growth, possibly due to the enhanced presence of placental insulin receptors on the maternal villous membrane early in gestation.

IFPA meeting 2016 workshop report II: Placental imaging, placenta and development of other organs, sexual dimorphism in placental function and trophoblast cell lines

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2016 there were twelve themed workshops, four of which are summarized in this report. These workshops addressed challenges, strengths and limitations of techniques and model systems for studying the placenta, as well as future directions for the following areas of placental research: 1) placental imaging; 2) sexual dimorphism; 3) placenta and development of other organs; 4) trophoblast cell lines.

IFPA Meeting 2013 Workshop Report I: diabetes in pregnancy, maternal dyslipidemia in pregnancy, oxygen in placental development, stem cells and pregnancy pathology

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2013 there were twelve themed workshops, four of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of pregnancy pathologies and placental metabolism: 1) diabetes in pregnancy; 2) lipids, fatty acids and the placenta; 3) oxygen in placental development and pathologies; 4) stem cells and pathologies.

IFPA meeting 2016 workshop report I: genomic communication, bioinformatics, trophoblast biology and transport systems

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2016 there were twelve themed workshops, four of which are summarized in this report. These workshops covered innovative technologies applied to new and traditional areas of placental research: 1) genomic communication; 2) bioinformatics; 3) trophoblast biology and pathology; 4) placental transport systems.

IFPA meeting 2015 workshop report I: placental mitochondrial function, transport systems and epigenetics

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2015 there were twelve themed workshops, three of which are summarized in this report. These workshops covered areas of placental regulation and nutrient handling: 1) placental epigenetics; 2) placental mitochondrial function; 3) placental transport systems.

Maternal obesity is not associated with placental lipid accumulation in women with high omega-3 fatty acid levels

INTRODUCTION Placentas of obese women have higher lipid content compared to lean women. We have previously shown that supplementation of overweight and obese women with omega-3 fatty acids decreases placental esterification pathways and total lipid content in a mid-western population (Ohio). We hypothesized that placental lipid accumulation and inflammation would be similar between lean and obese women living in a region of high omega-3 intake, such as Hawaii. METHODS Fifty-five healthy, normal glucose tolerant women from Honolulu Hawaii, dichotomized based on pre-pregnancy BMI into lean (BMI <25 kg/m2, n = 29) and obese (BMI >30 kg/m2, n = 26), were recruited at scheduled term cesarean delivery. Maternal plasma DHA levels were analyzed by mass spectrometry. Expression of key genes involved in fatty acid oxidation and esterification were measured in placental tissue using qPCR. Total lipids were extracted from placental tissue via the Folch method. TNF-α concentration was measured by enzyme-linked immunosorbent assay in placental lysates. RESULTS DHA levels were higher in lean women compared to obese women (P = 0.02). However, DHA levels in obese women in Hawaii were eight times higher compared to obese Ohioan women (P=<0.0001). Placental lipid content and expression of key genes involved in fatty acid oxidation and esterification were similar (P > 0.05) between lean and obese women in Hawaii. Furthermore, TNF-α placental lysates were not different between lean and obese women. CONCLUSIONS Though obese women in Hawaii have lower DHA levels compared to their lean counterparts, these levels remain over eight times as high as obese Ohioan women. These relatively high plasma omega-3 levels in obese women in Hawaii may suppress placental lipid esterification/storage and inflammation to the same levels of lean women, as seen previously in vitro.