Misao Nakanishi1,2, Nobuaki Funahashi3,4, Hideoki Fukuoka5,6, Takao Nammo3,7, Yuichi Sato8, Hajime Yoshihara9, Hajime Oishi1, Mamoru Tanaka10, Tetsu Yano1,11, Shigeki Minoura1,12, Norihiro Kato13, Kazuki Yasuda3,14. 1. Department of Obstetrics and Gynecology, Center Hospital, National Center for Global Health and Medicine, Tokyo, Japan. 2. Department of Obstetrics and Gynecology, Keio University Graduate School of Medicine, Tokyo, Japan. 3. Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan. 4. Division of Cancer Cell Research, Research Institute, Kanagawa Cancer Center, Kanagawa, Japan. 5. Department of Innovation Research, Waseda University Comprehensive Research Organization, Tokyo, Japan. 6. Department of Progressive DOHaD Research, Fukushima Medical University, Fukushima, Japan. 7. Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan. 8. Department of Obstetrics and Gynecology, Obstetrics and Gynecology Tatedebari Sato Hospital, Gunma, Japan. 9. Japan Community Health Care Organization, Sagamino Hospital Center of Perinatal Medicine, Kanagawa, Japan. 10. Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan. 11. Department of Obstetrics and Gynecology, Tokyo Yamate Medical Center, Tokyo, Japan. 12. Department of Obstetrics and Gynecology, Shinjuku City Medical Association Residents' Health Center, Tokyo, Japan. 13. Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan. 14. Department of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, Tokyo, Japan.
Abstract
AIM: We performed a birth cohort study involving 124 mother-infant pairs to investigate whether placental DNA methylation is associated with maternal choline status and fetal development. METHODS: Plasma choline concentration was assayed longitudinally in the 1st and 3rd trimesters and at term-pregnancy in mothers and cord blood. Placental DNA methylation was measured for 12 target candidate genes that are related to fetal growth, adipogenesis, lipid and energy metabolism, or long interspersed nuclear elements. RESULTS: Higher maternal plasma and cord blood choline levels at term tended to associate with lower birthweight (r = -0.246, P < 0.013; r = -0.290, P < 0.002) and body mass index (BMI) at birth (r = 0.344, P < 1E-3; r = -0.360, P < 1E-3). The correlation between maternal plasma choline level and cord blood choline level was relatively modest (r = 0.049, P = 0.639). There was an inverse correlation between placental DNA methylation at the retinoid X receptor alpha (RXRA) gene and maternal plasma choline level (r = -0.188 to r = -0.452, P = 0.043 to P < 1E-3 at three points). RXRA methylation level was positively associated with birthweight and BMI at birth (r = 0.306, P = 0.001; r = 0.390, P < 1E-3). Further, RXRA methylation was inversely correlated with RXRA gene expression level (r = 0.333, P < 1E-3). CONCLUSION: Our results suggest that the association between maternal choline status and placental RXRA methylation represents a potential fetal programing mechanism contributing to fetal growth.
AIM: We performed a birth cohort study involving 124 mother-infant pairs to investigate whether placental DNA methylation is associated with maternal choline status and fetal development. METHODS: Plasma choline concentration was assayed longitudinally in the 1st and 3rd trimesters and at term-pregnancy in mothers and cord blood. Placental DNA methylation was measured for 12 target candidate genes that are related to fetal growth, adipogenesis, lipid and energy metabolism, or long interspersed nuclear elements. RESULTS: Higher maternal plasma and cord blood choline levels at term tended to associate with lower birthweight (r = -0.246, P < 0.013; r = -0.290, P < 0.002) and body mass index (BMI) at birth (r = 0.344, P < 1E-3; r = -0.360, P < 1E-3). The correlation between maternal plasma choline level and cord blood choline level was relatively modest (r = 0.049, P = 0.639). There was an inverse correlation between placental DNA methylation at the retinoid X receptor alpha (RXRA) gene and maternal plasma choline level (r = -0.188 to r = -0.452, P = 0.043 to P < 1E-3 at three points). RXRA methylation level was positively associated with birthweight and BMI at birth (r = 0.306, P = 0.001; r = 0.390, P < 1E-3). Further, RXRA methylation was inversely correlated with RXRA gene expression level (r = 0.333, P < 1E-3). CONCLUSION: Our results suggest that the association between maternal choline status and placental RXRA methylation represents a potential fetal programing mechanism contributing to fetal growth.
Authors: Eleonora Rubini; Inge M M Baijens; Alex Horánszky; Sam Schoenmakers; Kevin D Sinclair; Melinda Zana; András Dinnyés; Régine P M Steegers-Theunissen; Melek Rousian Journal: Genes (Basel) Date: 2021-10-17 Impact factor: 4.096
Authors: Erika Chavira-Suárez; Luis Antonio Reyes-Castro; Itzel Ivonn López-Tenorio; Lilia Vargas-Hernández; Guadalupe L Rodríguez-González; Roberto Chavira; Paola Zárate-Segura; Aaron Domínguez-López; Felipe Vadillo-Ortega; Elena Zambrano Journal: Front Cell Dev Biol Date: 2022-08-16