Identification of placental nutrient transporters associated with intrauterine growth restriction and pre-eclampsia. 2018

Xiao Huang, and Pascale Anderle, and Lu Hostettler, and Marc U Baumann, and Daniel V Surbek, and Edgar C Ontsouka, and Christiane Albrecht
Swiss National Centre of Competence in Research, NCCR TransCure, University of Bern, Bern, Switzerland.

Gestational disorders such as intrauterine growth restriction (IUGR) and pre-eclampsia (PE) are main causes of poor perinatal outcomes worldwide. Both diseases are related with impaired materno-fetal nutrient transfer, but the crucial transport mechanisms underlying IUGR and PE are not fully elucidated. In this study, we aimed to identify membrane transporters highly associated with transplacental nutrient deficiencies in IUGR/PE. In silico analyses on the identification of differentially expressed nutrient transporters were conducted using seven eligible microarray datasets (from Gene Expression Omnibus), encompassing control and IUGR/PE placental samples. Thereby 46 out of 434 genes were identified as potentially interesting targets. They are involved in the fetal provision with amino acids, carbohydrates, lipids, vitamins and microelements. Targets of interest were clustered into a substrate-specific interaction network by using Search Tool for the Retrieval of Interacting Genes. The subsequent wet-lab validation was performed using quantitative RT-PCR on placentas from clinically well-characterized IUGR/PE patients (IUGR, n = 8; PE, n = 5; PE+IUGR, n = 10) and controls (term, n = 13; preterm, n = 7), followed by 2D-hierarchical heatmap generation. Statistical evaluation using Kruskal-Wallis tests was then applied to detect significantly different expression patterns, while scatter plot analysis indicated which transporters were predominantly influenced by IUGR or PE, or equally affected by both diseases. Identified by both methods, three overlapping targets, SLC7A7, SLC38A5 (amino acid transporters), and ABCA1 (cholesterol transporter), were further investigated at the protein level by western blotting. Protein analyses in total placental tissue lysates and membrane fractions isolated from disease and control placentas indicated an altered functional activity of those three nutrient transporters in IUGR/PE. Combining bioinformatic analysis, molecular biological experiments and mathematical diagramming, this study has demonstrated systematic alterations of nutrient transporter expressions in IUGR/PE. Among 46 initially targeted transporters, three significantly regulated genes were further investigated based on the severity and the disease specificity for IUGR and PE. Confirmed by mRNA and protein expression, the amino acid transporters SLC7A7 and SLC38A5 showed marked differences between controls and IUGR/PE and were regulated by both diseases. In contrast, ABCA1 may play an exclusive role in the development of PE.

UI MeSH Term Description Entries
D007231 Infant, Newborn An infant during the first 28 days after birth. Neonate,Newborns,Infants, Newborn,Neonates,Newborn,Newborn Infant,Newborn Infants
D010920 Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (CHORIONIC VILLI) derived from TROPHOBLASTS and a maternal portion (DECIDUA) derived from the uterine ENDOMETRIUM. The placenta produces an array of steroid, protein and peptide hormones (PLACENTAL HORMONES). Placentoma, Normal,Placentome,Placentas,Placentomes
D011225 Pre-Eclampsia A complication of PREGNANCY, characterized by a complex of symptoms including maternal HYPERTENSION and PROTEINURIA with or without pathological EDEMA. Symptoms may range between mild and severe. Pre-eclampsia usually occurs after the 20th week of gestation, but may develop before this time in the presence of trophoblastic disease. Toxemias, Pregnancy,EPH Complex,EPH Gestosis,EPH Toxemias,Edema-Proteinuria-Hypertension Gestosis,Gestosis, EPH,Hypertension-Edema-Proteinuria Gestosis,Preeclampsia,Preeclampsia Eclampsia 1,Pregnancy Toxemias,Proteinuria-Edema-Hypertension Gestosis,Toxemia Of Pregnancy,1, Preeclampsia Eclampsia,1s, Preeclampsia Eclampsia,EPH Toxemia,Eclampsia 1, Preeclampsia,Eclampsia 1s, Preeclampsia,Edema Proteinuria Hypertension Gestosis,Gestosis, Edema-Proteinuria-Hypertension,Gestosis, Hypertension-Edema-Proteinuria,Gestosis, Proteinuria-Edema-Hypertension,Hypertension Edema Proteinuria Gestosis,Of Pregnancies, Toxemia,Of Pregnancy, Toxemia,Pre Eclampsia,Preeclampsia Eclampsia 1s,Pregnancies, Toxemia Of,Pregnancy Toxemia,Pregnancy, Toxemia Of,Proteinuria Edema Hypertension Gestosis,Toxemia Of Pregnancies,Toxemia, EPH,Toxemia, Pregnancy,Toxemias, EPH
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D005260 Female Females
D005317 Fetal Growth Retardation Failure of a FETUS to attain expected GROWTH. Growth Retardation, Intrauterine,Intrauterine Growth Retardation,Fetal Growth Restriction,Intrauterine Growth Restriction
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D016022 Case-Control Studies Comparisons that start with the identification of persons with the disease or outcome of interest and a control (comparison, referent) group without the disease or outcome of interest. The relationship of an attribute is examined by comparing both groups with regard to the frequency or levels of outcome over time. Case-Base Studies,Case-Comparison Studies,Case-Referent Studies,Matched Case-Control Studies,Nested Case-Control Studies,Case Control Studies,Case-Compeer Studies,Case-Referrent Studies,Case Base Studies,Case Comparison Studies,Case Control Study,Case Referent Studies,Case Referrent Studies,Case-Comparison Study,Case-Control Studies, Matched,Case-Control Studies, Nested,Case-Control Study,Case-Control Study, Matched,Case-Control Study, Nested,Case-Referent Study,Case-Referrent Study,Matched Case Control Studies,Matched Case-Control Study,Nested Case Control Studies,Nested Case-Control Study,Studies, Case Control,Studies, Case-Base,Studies, Case-Comparison,Studies, Case-Compeer,Studies, Case-Control,Studies, Case-Referent,Studies, Case-Referrent,Studies, Matched Case-Control,Studies, Nested Case-Control,Study, Case Control,Study, Case-Comparison,Study, Case-Control,Study, Case-Referent,Study, Case-Referrent,Study, Matched Case-Control,Study, Nested Case-Control
D055815 Young Adult A person between 19 and 24 years of age. Adult, Young,Adults, Young,Young Adults

Related Publications

Xiao Huang, and Pascale Anderle, and Lu Hostettler, and Marc U Baumann, and Daniel V Surbek, and Edgar C Ontsouka, and Christiane Albrecht
June 2007, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology,
Xiao Huang, and Pascale Anderle, and Lu Hostettler, and Marc U Baumann, and Daniel V Surbek, and Edgar C Ontsouka, and Christiane Albrecht
January 2016, Frontiers in physiology,
Xiao Huang, and Pascale Anderle, and Lu Hostettler, and Marc U Baumann, and Daniel V Surbek, and Edgar C Ontsouka, and Christiane Albrecht
February 2024, Minerva obstetrics and gynecology,
Xiao Huang, and Pascale Anderle, and Lu Hostettler, and Marc U Baumann, and Daniel V Surbek, and Edgar C Ontsouka, and Christiane Albrecht
August 1998, Pediatric research,
Xiao Huang, and Pascale Anderle, and Lu Hostettler, and Marc U Baumann, and Daniel V Surbek, and Edgar C Ontsouka, and Christiane Albrecht
December 2008, Journal of clinical pathology,
Xiao Huang, and Pascale Anderle, and Lu Hostettler, and Marc U Baumann, and Daniel V Surbek, and Edgar C Ontsouka, and Christiane Albrecht
September 2007, BJOG : an international journal of obstetrics and gynaecology,
Xiao Huang, and Pascale Anderle, and Lu Hostettler, and Marc U Baumann, and Daniel V Surbek, and Edgar C Ontsouka, and Christiane Albrecht
May 2011, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology,
Xiao Huang, and Pascale Anderle, and Lu Hostettler, and Marc U Baumann, and Daniel V Surbek, and Edgar C Ontsouka, and Christiane Albrecht
January 2003, Placenta,
Xiao Huang, and Pascale Anderle, and Lu Hostettler, and Marc U Baumann, and Daniel V Surbek, and Edgar C Ontsouka, and Christiane Albrecht
October 2003, BJOG : an international journal of obstetrics and gynaecology,
Xiao Huang, and Pascale Anderle, and Lu Hostettler, and Marc U Baumann, and Daniel V Surbek, and Edgar C Ontsouka, and Christiane Albrecht
September 2018, The Journal of nutritional biochemistry,
Copied contents to your clipboard!