Suvo Chatterjee1, Xuehuo Zeng1, Marion Ouidir1, Markos Tesfaye2, Cuilin Zhang1, Fasil Tekola-Ayele3. 1. Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, 20892, MD, USA. 2. Section of Sensory Science and Metabolism (SenSMet), National Institute on Alcohol Abuse and Alcoholism & National Institute of Nursing Research, National Institutes of Health, Bethesda, MD, 20814, USA. 3. Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, 20892, MD, USA. Electronic address: ayeleft@mail.nih.gov.
Abstract
INTRODUCTION: Small for gestational age at birth (SGA), often a consequence of placental dysfunction, is a risk factor for neonatal morbidity and later life cardiometabolic diseases. There are sex differences in placental gene expression and fetal growth. Here, we investigated sex-specific associations between gene expression in human placenta measured using RNA sequencing and SGA status using data from ethnic diverse pregnant women in the NICHD Fetal Growth Studies cohort (n = 74). METHODS: Gene expression measures were obtained using RNA-Sequencing and differential gene expression between SGA (birthweight <10th percentile) and appropriate for gestational age (AGA: ≥10th and <90th percentile) was tested separately in males (12 SGA and 27 AGA) and females (9 SGA and 26 AGA) using a weighted mean of log ratios method with adjustment for mode of delivery and ethnicity. RESULTS: At 5% false discovery rate (FDR), we identified 40 differentially expressed genes (DEGs) related to SGA status among males (95% up- and 5% down-regulated) and 314 DEGs among females (32.5% up- and 67.5% down-regulated). Seven female-specific DEGs overlapped with known imprinted genes (AXL, CYP24A1, GPR1, PLAGL1, CMTM1, DLX5, LY6D). The DEGs in males were significantly enriched for immune response and inflammation signaling pathways whereas the DEGs in females were enriched for organ development signaling pathways (FDR<0.05). Sex-combined analysis identified no additional DEGs, rather 98% of the sex-specific DEGs were no longer significant and the remaining 2% were attenuated. DISCUSSION: This study revealed sex-specific human placental gene expression changes and molecular pathways associated with SGA and underscored that unravelling the pathogenesis of SGA warrants consideration of fetal sex as a biological variable. TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov, Unique identifier: NCT00912132. Published by Elsevier Ltd.
INTRODUCTION: Small for gestational age at birth (SGA), often a consequence of placental dysfunction, is a risk factor for neonatal morbidity and later life cardiometabolic diseases. There are sex differences in placental gene expression and fetal growth. Here, we investigated sex-specific associations between gene expression in human placenta measured using RNA sequencing and SGA status using data from ethnic diverse pregnant women in the NICHD Fetal Growth Studies cohort (n = 74). METHODS: Gene expression measures were obtained using RNA-Sequencing and differential gene expression between SGA (birthweight <10th percentile) and appropriate for gestational age (AGA: ≥10th and <90th percentile) was tested separately in males (12 SGA and 27 AGA) and females (9 SGA and 26 AGA) using a weighted mean of log ratios method with adjustment for mode of delivery and ethnicity. RESULTS: At 5% false discovery rate (FDR), we identified 40 differentially expressed genes (DEGs) related to SGA status among males (95% up- and 5% down-regulated) and 314 DEGs among females (32.5% up- and 67.5% down-regulated). Seven female-specific DEGs overlapped with known imprinted genes (AXL, CYP24A1, GPR1, PLAGL1, CMTM1, DLX5, LY6D). The DEGs in males were significantly enriched for immune response and inflammation signaling pathways whereas the DEGs in females were enriched for organ development signaling pathways (FDR<0.05). Sex-combined analysis identified no additional DEGs, rather 98% of the sex-specific DEGs were no longer significant and the remaining 2% were attenuated. DISCUSSION: This study revealed sex-specific human placental gene expression changes and molecular pathways associated with SGA and underscored that unravelling the pathogenesis of SGA warrants consideration of fetal sex as a biological variable. TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov, Unique identifier: NCT00912132. Published by Elsevier Ltd.
Entities:
Keywords:
Developmental origins of health and disease; Human placenta; Pregnancy; Sexual dimorphism; Small for gestational age
Authors: Norbert Vaessen; Joop A Janssen; Peter Heutink; Albert Hofman; Steven W J Lamberts; Ben A Oostra; Huibert A P Pols; Cornelia M van Duijn Journal: Lancet Date: 2002-03-23 Impact factor: 79.321
Authors: Thorhildur Juliusdottir; Valgerdur Steinthorsdottir; Lilja Stefansdottir; Gardar Sveinbjornsson; Erna V Ivarsdottir; Rosa B Thorolfsdottir; Jon K Sigurdsson; Vinicius Tragante; Kristjan E Hjorleifsson; Anna Helgadottir; Michael L Frigge; Gudmundur Thorgeirsson; Rafn Benediktsson; Emil L Sigurdsson; David O Arnar; Thora Steingrimsdottir; Ingileif Jonsdottir; Hilma Holm; Daniel F Gudbjartsson; Gudmar Thorleifsson; Unnur Thorsteinsdottir; Kari Stefansson Journal: Nat Genet Date: 2021-07-19 Impact factor: 38.330
Authors: Sam Buckberry; Tina Bianco-Miotto; Stephen J Bent; Gustaaf A Dekker; Claire T Roberts Journal: Mol Hum Reprod Date: 2014-05-27 Impact factor: 4.025