title: Placental Up-Regulation of Leptin and ARMS2 is Associated with Growth Discordance in Monochorionic Diamniotic Twin Pregnancies.
abstract: Fetal growth discordance is a relatively common complication of monochorionic diamniotic (MCDA) twin pregnancies and is caused by a combination of maternal and placental factors. The aim of the study was to survey placental gene expression patterns and identify genes associated with growth discordance. Clinical samples comprised eight growth-discordant MCDA twin placentas (31+3-34+4 weeks gestational age) and six growth-concordant twin placentas (31+2-37 weeks gestational age). Gene expression libraries were constructed from placental biopsy samples and analyzed by RNA-sequencing. The distribution and relative abundance of mRNA transcripts expressed in the smaller and larger placentas from growth-discordant and concordant MCDA twins was remarkably similar. However, leptin (LEP) and age-related maculopathy susceptibility 2 (ARMS2) mRNA levels were exclusively up-regulated in all of the eight smaller growth-discordant twin placentas. Quantitative real-time PCR of independent biopsy samples confirmed the levels of differential mRNA expression for both genes. Immunohistochemical analysis of tissue sections from matching twin placentas showed increased leptin expression in 5-10% of blood vessel cells of the smaller placenta and marginally higher levels of ARMS2 expression in the microvillous membrane of the smaller placenta. Based on these findings, we speculate that up-regulation of leptin and ARMS2 forms part of an important survival mechanism to compensate for placental growth discordance. Since, leptin and ARMS2 are both expressed as soluble proteins, they may have clinical potential as measurable biomarkers for predicting the onset of growth discordance in MCDA twin pregnancies.
authors.affiliation: Fetal Medicine Unit and Prenatal Diagnosis Center,Department of Obstetrics,Shanghai First Maternity and Infant Hospital,Tongji University School of Medicine,Shanghai,China.
authors.forename: Luming
authors.initials: L
authors.lastname: Sun
authors.affiliation: Fetal Medicine Unit and Prenatal Diagnosis Center,Department of Obstetrics,Shanghai First Maternity and Infant Hospital,Tongji University School of Medicine,Shanghai,China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Fetal Medicine Unit and Prenatal Diagnosis Center,Department of Obstetrics,Shanghai First Maternity and Infant Hospital,Tongji University School of Medicine,Shanghai,China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: School of Public Health of Fudan University,Shanghai,China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Berry Genomics Corporation,Chaoyang District,Beijing,China.
authors.forename: Ling
authors.initials: L
authors.lastname: Shang
authors.affiliation: Berry Genomics Corporation,Chaoyang District,Beijing,China.
authors.forename: Jianguang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Public Health of Fudan University,Shanghai,China.
authors.forename: Junqing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Berry Genomics Corporation,Chaoyang District,Beijing,China.
authors.forename: David S
authors.initials: DS
authors.lastname: Cram
mesh_terms: D005260:Female; D015723:Gene Library; D005865:Gestational Age; D006801:Humans; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D059285:Pregnancy, Twin / Q000235:genetics*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D014430:Twins, Monozygotic / Q000235:genetics; D015854:Up-Regulation
chemical_list: C514392:ARMS2 protein, human; D020738:Leptin; D011506:Proteins
keywords: ARMS2; RNA sequencing; growth discordance; leptin; monochorionic diamniotic; placenta