Fatty acids alter glycerolipid metabolism and induce lipid droplet formation, syncytialisation and cytokine production in human trophoblasts with minimal glucose effect or interaction.

The diabetic pregnancy is characterized by maternal hyperglycaemia and dyslipidaemia, such that placental trophoblast cells are exposed to both. The objective was to determine the effects of hyperglycaemia, elevated non-esterified fatty acids (NEFA) and their interactions on trophoblast cell metabolism and function. Trophoblasts were isolated from normal term human placentas and established in culture for 16 h prior to experiments. Glucose utilisation, fatty acid oxidation and fatty acid esterification were determined using radiolabelled metabolic tracer methodology at various glucose and NEFA concentrations. Trophoblast lipid droplet formation including adipophilin mRNA expression, viability, apoptosis, syncytialisation, secretion of hormones and pro-inflammatory cytokines were also assessed. Glucose utilisation via glycolysis was near maximal at the low physiological glucose concentration of 4mM; whereas NEFA esterification into triacylglycerol and diacylglycerol increased linearly with increasing NEFA concentrations without evidence of plateau. Culture of trophoblasts in 0.25 mM NEFA for 24h upregulated fatty acid esterification processes, inhibited fatty acid oxidation, inhibited glycerol release (a marker of lipolysis) and promoted adipophilin and lipid droplet formation, all consistent with upregulation of fatty acid storage and buffering capacity. NEFA also promoted trophoblast syncytialisation and TNFalpha, IL-1beta, IL-6 and IL-10 production without effects on cell viability, apoptosis or hormone secretion. Hyperglycaemia caused intracellular glycogen accumulation and reduced lipid droplet formation, but had no other effects on trophoblast metabolism or function. NEFA have effects on trophoblast metabolism and function, mostly independent of glucose, that may have protective as well as pathophysiological roles in pregnancies complicated by diabetes and/or obesity.

Maternal and cord blood levels of insulin-like growth factors--I and--II and insulin-like growth factor binding protein-1: correlation with birth weight and maternal anthropometric indices.

OBJECTIVES: To study the correlation of maternal and cord blood insulin like growth factor (IGF)-I and -II and IGF binding protein (IGFBP)-1 levels with birth weight and maternal anthropometric indices. DESIGN: Longitudinal prospective study. SETTING: Academic Institutions and a Tertiary Care Maternity Hospital. PARTICIPANTS: Women with uncomplicated singleton pregnancy (N = 35) and their newborns. MEASUREMENTS: Maternal weight, height, symphysiofundal height and serum levels of IGF-I, IGF-II, IGFBP-1 were measured thrice during the antenatal period, within 24 h of delivery and at 6 weeks and 6 months postpartum. Newborn anthropometric indices were recorded at birth, and at 6 weeks and 6 months of age. Cord blood levels of IGF-1, IGF-II, IGFBP-1, paternal height and weight, and placental weight measured. RESULTS: Maternal and cord blood IGF-I levels were lower than values reported for Caucasians. All newborns showed adequate growth at birth, and up to 6 months of age. Cord blood IGF-1 positively correlated with chest circumference (r = 0.4532, P = 0.0262), IGFBP-1, negatively with birth weight (r = -0.4024, P = 0.0461) and IGF-II had no effect. Cord blood IGF-I positively correlated with maternal levels at 28 +/- 2 (r = 0.4571, P = 0.0247) and 36 +/- 2 (r = 0.4291, P = 0.0364) weeks of amenorrhoea, whereas IGF-II and IGFBP-1 did not correlate with maternal values. Maternal IGF-I, IGF-II and IGFBP-1 did not correlate with newborn or maternal anthropometric indices. Placental weight correlated significantly with birth weight (r = 0.5299, P = 0.0348) and head circumference (r = 0.5031, P = 0.0470). CONCLUSIONS: Cord blood IGFBP-1 and placental weight appear to be determinants of birth weight variation even among appropriately grown for gestational age newborns.

Insulin-like growth factors-I and -II and insulin-like growth factor binding protein-1 during normal pregnancy: pattern of secretion and correlation with other placental hormones.

OBJECTIVES: To describe pattern of secretion of insulin-like growth factor (IGF)-I, IGF-II, IGF binding protein (IGFBP)-1 and their correlation with each other and major placental hormones during normal pregnancy. DESIGN: Longitudinal study. SETTING: Academic Institutions and a Tertiary Care Maternity Hospital. PARTICIPANTS: Healthy women with singleton uncomplicated pregnancies (N = 35). MEASUREMENTS: Serum levels of IGF-I, IGF-II, IGFBP-1, chorionic gonadotrophin (HCG), placental lactogen (HPL), prolactin, oestradiol and progesterone were studied thrice during the antenatal period and within 24 h of delivery. RESULTS: IGF-I, IGFBP-1, HPL, prolactin, oestradiol and progesterone increased and HCG decreased significantly with advancing gestation (Repeated measures ANOVA: P < 0.01 to 0.0001). IGF-II levels were not significantly affected by period of gestation. Significant negative correlations (multiple regression analysis) were seen between IGFBP-1 and prolactin at 28 +/- 2 (P = 0.0226) and 36 +/- 2 (P = 0.0417) weeks of amenorrhoea (WOA) and between oestradiol and IGF-II at 36 +/- 2 WOA (P = 0.037). Prolactin and IGF-I at 14 +/- 2 WOA (P = 0.0225) and progesterone and IGFBP-1 at 28 +/- 2 WOA (P = 0.0216) correlated positively. CONCLUSIONS: Maternal IGF-I and IGFBP-1 but not IGF-II significantly increase as pregnancy advances. Components of the IGF system regulate or are affected by some of the placental hormones and the effects vary with the period of gestation.