Sifang Kathy Zhao1, Edwina H Yeung1, Marion Ouidir1, Stefanie N Hinkle1,2, Katherine L Grantz1, Susanna D Mitro1, Jing Wu3, Danielle R Stevens1, Suvo Chatterjee1, Fasil Tekola-Ayele1, Cuilin Zhang1,4,5. 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, MD, USA. 2. Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 3. Glotech, Inc, Rockville, MD, USA. 4. Global Center for Asian Women's Health, Bia-Echo Asia Centre for Reproductive Longevity & Equality (ACRLE), Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 5. Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Abstract
BACKGROUND: Physical activity (PA) prior to and during pregnancy may have intergenerational effects on offspring health through placental epigenetic modifications. We are unaware of epidemiologic studies on longitudinal PA and placental DNA methylation. OBJECTIVES: We evaluated the association between PA before and during pregnancy and placental DNA methylation. METHODS: Placental tissues were obtained at delivery and methylation was measured using HumanMethylation450 Beadchips for participants in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singletons among 298 participants. Using the Pregnancy Physical Activity Questionnaire, women recalled periconception PA (past 12 mo) at 8-13 wk of gestation and PA since last visit at 4 follow-up visits at 16-22, 24-29, 30-33, and 34-37 wk. We conducted linear regression for associations of PA at each visit with methylation controlling for false discovery rate (FDR). Top 100 CpGs were queried for enrichment of functional pathways using Ingenuity Pathway Analysis. RESULTS: Periconception PA was significantly associated with 1 CpG site. PA since last visit for visits 1-4 was associated with 2, 2, 8, and 0 CpGs (log fold changes ranging from -0.0319 to 0.0080, after controlling for FDR). The largest change in methylation occurred at a site in TIMP2 , which is known to encode a protein critical for vasodilation, placentation, and uterine expansion during pregnancy (log fold change: -0.05; 95% CI: -0.06, -0.03 per metabolic equivalent of task-h/wk at 30-33 wk). Most significantly enriched pathways include cardiac hypertrophy signaling, B-cell receptor signaling, and netrin signaling. Significant CpGs and enriched pathways varied by visit. CONCLUSIONS: Recreational PA in the year prior and during pregnancy was associated with placental DNA methylation. The associated CpG sites varied based on timing of PA. If replicated, the findings may inform the mechanisms underlying the impacts of PA on placenta health. This study was registered at clinicaltrials.gov as NCT00912132.
BACKGROUND: Physical activity (PA) prior to and during pregnancy may have intergenerational effects on offspring health through placental epigenetic modifications. We are unaware of epidemiologic studies on longitudinal PA and placental DNA methylation. OBJECTIVES: We evaluated the association between PA before and during pregnancy and placental DNA methylation. METHODS: Placental tissues were obtained at delivery and methylation was measured using HumanMethylation450 Beadchips for participants in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singletons among 298 participants. Using the Pregnancy Physical Activity Questionnaire, women recalled periconception PA (past 12 mo) at 8-13 wk of gestation and PA since last visit at 4 follow-up visits at 16-22, 24-29, 30-33, and 34-37 wk. We conducted linear regression for associations of PA at each visit with methylation controlling for false discovery rate (FDR). Top 100 CpGs were queried for enrichment of functional pathways using Ingenuity Pathway Analysis. RESULTS: Periconception PA was significantly associated with 1 CpG site. PA since last visit for visits 1-4 was associated with 2, 2, 8, and 0 CpGs (log fold changes ranging from -0.0319 to 0.0080, after controlling for FDR). The largest change in methylation occurred at a site in TIMP2 , which is known to encode a protein critical for vasodilation, placentation, and uterine expansion during pregnancy (log fold change: -0.05; 95% CI: -0.06, -0.03 per metabolic equivalent of task-h/wk at 30-33 wk). Most significantly enriched pathways include cardiac hypertrophy signaling, B-cell receptor signaling, and netrin signaling. Significant CpGs and enriched pathways varied by visit. CONCLUSIONS: Recreational PA in the year prior and during pregnancy was associated with placental DNA methylation. The associated CpG sites varied based on timing of PA. If replicated, the findings may inform the mechanisms underlying the impacts of PA on placenta health. This study was registered at clinicaltrials.gov as NCT00912132.
Authors: Joji Kusuyama; Ana Barbara Alves-Wagner; Royce H Conlin; Nathan S Makarewicz; Brent G Albertson; Noah B Prince; Shio Kobayashi; Chisayo Kozuka; Magnus Møller; Mette Bjerre; Jens Fuglsang; Emily Miele; Roeland J W Middelbeek; Yang Xiudong; Yang Xia; Léa Garneau; Jayonta Bhattacharjee; Céline Aguer; Mary Elizabeth Patti; Michael F Hirshman; Niels Jessen; Toshihisa Hatta; Per Glud Ovesen; Kristi B Adamo; Eva Nozik-Grayck; Laurie J Goodyear Journal: Cell Metab Date: 2021-03-25 Impact factor: 27.287
Authors: Peter J Cook; Bong Gun Ju; Francesca Telese; Xiangting Wang; Christopher K Glass; Michael G Rosenfeld Journal: Nature Date: 2009-02-22 Impact factor: 49.962