A pinboard by
Victoria Sandler

Endocrinology Fellow, Northwestern University


Maternal obesity, hyperglycemia and insulin resistance impact fetal metabolism and have implications for chronic disease in offspring. Given sex differences in newborn anthropometrics, it is important to understand how fetal sex differences affect the association of maternal BMI and glycemia with maternal metabolites and fetal traits. Using phenotype data and targeted and non-targeted metabolomic assays from 400 European ancestry mothers, we investigated sex-specific differences in the associations of maternal phenotypes and maternal metabolites at the time of oral glucose tolerance test (OGTT) at 28 weeks gestation and newborn cord blood metabolites at birth. We found sex differences in the association of maternal phenotype with maternal 3rd trimester metabolites.


Steroid metabolome in fetal and maternal body fluids in human late pregnancy.

Abstract: Despite the extensive research during the last six decades the fundamental questions concerning the role of steroids in the initiation of human parturition and origin and function of some steroids in pregnancy were not definitely answered. Based on steroid metabolomic data found in the literature and our so far unpublished results, we attempted to bring new insights concerning the role of steroids in the sustaining and termination of human pregnancy, and predictive value of these substances for estimation of term. We also aimed to explain enigmas concerning the biosynthesis of progesterone and its bioactive catabolites considering the conjunctions between placental production of CRH, synthesis of bioactive steroids produced by fetal adrenal, localization of placental oxidoreductases and sustaining of human pregnancy. Evaluation of data available in the literature, including our recent findings as well as our new unpublished data indicates increasing progesterone synthesis and its concurrently increasing catabolism with approaching parturition, confirms declining production of pregnancy sustaining 5β-pregnane steroids providing uterine quiescence in late pregnancy, increased sulfation of further neuroinhibiting and pregnancy sustaining steroids. In contrast to the established concept considering LDL cholesterol as the primary substrate for progesterone synthesis in pregnancy, our data demonstrates the functioning of alternative mechanism for progesterone synthesis, which is based on the utilization of fetal pregnenolone sulfate for progesterone production in placenta. Close relationships were found between localization of placental oxidoreductases and consistently higher levels of sex hormones, neuroactive steroids and their metabolites in the oxidized form in the fetus and in the reduced form in the maternal compartment.

Pub.: 29 Jun '10, Pinned: 19 Jun '17

Maternal-fetal hepatic and placental metabolome profiles are associated with reduced fetal growth in a rat model of maternal obesity

Abstract: Maternal obesity is associated with a range of pregnancy complications, including fetal growth restriction (FGR), whereby a fetus fails to reach its genetically determined growth. Placental insufficiency and reduced nutrient transport play a role in the onset of FGR.Metabolomic profiling was used to reveal altered maternal and fetal metabolic pathways in a model of diet induced obesity during pregnancy, leading to reduced fetal growth.We examined the metabolome of maternal and fetal livers, and placenta following a high fat and salt intake. Sprague–Dawley rats were assigned to (a) control diet (CD; 1 % salt, 10 % kcal from fat), (b) high salt diet (SD; 4 % salt, 10 % kcal from fat), (c) high fat diet (HF; 1 % salt, 45 % kcal from fat) or (d) high-fat high-salt diet (HFSD; 4 % salt, 45 % kcal from fat) 21 days prior to pregnancy and during gestation. Metabolites from maternal and fetal livers, and placenta were identified using gas and liquid chromatography combined with mass spectrometry.Maternal HF intake resulted in reduced fetal weight. Altered metabolite profiles were observed in the HF maternal and fetal liver, and placenta. Polyunsaturated fatty acid metabolism was significantly altered in maternal and fetal liver by maternal fat intake.Excess of linoleic and α-linoleic acid (essential fatty acids) may be detrimental during placentation and associated with a reduction in fetal weight. Additionally, maternal, placental and fetal response to increased fat consumption seems likely to involve palmitoleic acid utilization as an adaptive response during maternal obesity.

Pub.: 15 Mar '16, Pinned: 19 Jun '17

New biomarkers for diagnosis and management of polycystic ovary syndrome.

Abstract: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting young women. Even though the definition of PCOS has changed over the years, all diagnostic criteria include two or more of the following: oligomenorrhea/oligoovulation/anovulation, androgen excess and polycystic ovaries (PCO). Traditional method of assessing the ovarian morphology has been transvaginal pelvic ultrasound. Recent studies support that serum anti-Mullerian hormone (AMH) levels correlate with the number of ovarian follicles and cysts. Hence, measurement of AMH is adequate to make the diagnosis. Traditionally, hyperandrogenemia has been assessed by measuring total-testosterone. The literature stresses the importance of sex hormone binding globulin (SHBG) measurements and bioavailable-testosterone and free-testosterone calculations, because insulin resistance decreases SHBG, lowers total-testosterone, and leads to under-estimation of bioavailable- and free-testosterone. Since 50-60% of PCOS patients have metabolic syndrome, assessment of metabolic risk is also necessary. It is important to diagnose insulin resistance before development of glucose intolerance and diabetes. This requires measurements of not only plasma glucose but also insulin concentrations. Determination of HgBA1 can be informative as well. This review aims to present an accurate and cost-effective approach to diagnosis and management of PCOS.

Pub.: 19 Jun '17, Pinned: 19 Jun '17