title: Folate deficiency impairs decidualization and alters methylation patterns of the genome in mice.
abstract: Existing evidence suggests that adverse pregnancy outcomes are closely related with dietary factors. Previous studies in mice have focused on the harm of folate deficiency (FD) on development of embryo, while the effect of low maternal folate levels on maternal intrauterine environment during early pregnancy remains unclear. Since our previous study found that FD treatment of mice causes no apparent defects in embryo implantation but is accompanied by female subfertility, we next chose to investigate a potential role of FD on molecular events after implantation. We observed that the decidual bulges began to be stunted on pregnancy day 6. The results of functional experiments in vivo and in vitro showed that FD inhibited the process of endometrial decidualization. It has been confirmed that DNA methylation participates in decidualization, and folate as a methyl donor could change the methylation patterns of genes. Thus, we hypothesized that FD impairs maternal endometrial decidualization by altering the methylation profiles of related genes. Reduced representation bisulphite sequencing was carried out to detect the methylation profiles of endometrium on pregnancy day 6-8, which is equivalent to the decidualization period in mice. The results confirmed that FD changes the methylation patterns of genome, and GO analysis of the differentially methylated regions revealed that the associated genes mainly participate in biological adhesion, biological regulation, cell proliferation, development, metabolism and signalling. In addition, we found some candidates for regulators of decidual transformation, such as Nr1h3 and Nr5a1. The data indicate that FD inhibits decidualization, possibly by altering methylation patterns of the genome in mice.
authors.affiliation: Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Box 197, No.1 Yixueyuan Road, Yuzhong District, 400016 Chongqing, PR China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Geng
authors.affiliation: Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Box 197, No.1 Yixueyuan Road, Yuzhong District, 400016 Chongqing, PR China.
authors.forename: Rufei
authors.initials: R
authors.lastname: Gao
authors.affiliation: Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Box 197, No.1 Yixueyuan Road, Yuzhong District, 400016 Chongqing, PR China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Box 197, No.1 Yixueyuan Road, Yuzhong District, 400016 Chongqing, PR China.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Box 197, No.1 Yixueyuan Road, Yuzhong District, 400016 Chongqing, PR China.
authors.forename: Xinggui
authors.initials: X
authors.lastname: Liao
authors.affiliation: Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Box 197, No.1 Yixueyuan Road, Yuzhong District, 400016 Chongqing, PR China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Box 197, No.1 Yixueyuan Road, Yuzhong District, 400016 Chongqing, PR China.
authors.forename: Shangjing
authors.initials: S
authors.lastname: Liu
authors.affiliation: Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Box 197, No.1 Yixueyuan Road, Yuzhong District, 400016 Chongqing, PR China.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Box 197, No.1 Yixueyuan Road, Yuzhong District, 400016 Chongqing, PR China.
authors.forename: Yingxiong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Box 197, No.1 Yixueyuan Road, Yuzhong District, 400016 Chongqing, PR China hejunlin_11@aliyun.com.
authors.forename: Junlin
authors.initials: J
authors.lastname: He
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019175:DNA Methylation / Q000235:genetics* / Q000502:physiology; D003656:Decidua / Q000166:cytology / Q000378:metabolism*; D010064:Embryo Implantation / Q000235:genetics* / Q000502:physiology; D004717:Endometrium / Q000166:cytology / Q000378:metabolism; D005260:Female; D005494:Folic Acid Deficiency / Q000150:complications* / Q000235:genetics*; D051379:Mice; D011247:Pregnancy
keywords: DNA methylation; RRBS; decidualization; folate