title: Uterine Expression of NDRG4 Is Induced by Estrogen and Up-Regulated during Embryo Implantation Process in Mice.
abstract: Embryo implantation is an essential step for the establishment of pregnancy and dynamically regulated by estrogen and progesterone. NDRG4 (N-myc down-regulated gene 4) is a tumor suppressor that participates in cell survival, tumor invasion and angiogenesis. The objective of this study was to preliminarily explore the role of NDRG4 in embryo implantation. By immunohistochemistry (IHC) and quantitive RT-PCR (qRT-PCR), we found that uterine expression of NDRG4 was increased along with puberal development, and its expression in adult females reached the peak at the estrus stage during the estrus cycle. Furthermore, uterine NDRG4 expression was significantly induced by the treatment of estradiol (E2) both in pre-puberty females and ovariectomized adult females. Uterine expression pattern of NDRG4 during the peri-implantation period in mice was determined by IHC, qRT-PCR and Western blot. It was observed that NDRG4 expression was up-regulated during the implantation process, and its expression level at the implantation sites was significantly higher than that at the inter-implantation sites. Meanwhile, an increased expression in NDRG4 was associated with artificial decidualization as well as the activation of delayed implantation. By qRT-PCR and Western blot, we found that the in vitro decidualization of endometrial stromal cells (ESCs) was accompanied by up-regulation of NDRG4 expression, whereas knockdown of its expression in these cells by siRNA inhibited the decidualization process. In addition, Western blot analysis showed that NDRG4 protein expression was decreased in human villus tissues of recurrent miscarriage (RM) patients compared to normal pregnant women. Collectively, these data suggested that uterine NDRG4 expression could be induced by estrogen, and NDRG4 might play an important role during early pregnancy.
authors.affiliation: NPFPC Key Lab of Reproduction Regulation, SIPPR, School of Pharmacy, Fudan University, Shanghai, 200032, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.affiliation: The Second Hospital of Tianjin Medical University, Tianjin, 300211, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gu
authors.affiliation: NPFPC Key Lab of Reproduction Regulation, SIPPR, School of Pharmacy, Fudan University, Shanghai, 200032, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The Second Hospital of Tianjin Medical University, Tianjin, 300211, China.
authors.forename: Jian-Mei
authors.initials: JM
authors.lastname: Wang
authors.affiliation: NPFPC Key Lab of Reproduction Regulation, SIPPR, School of Pharmacy, Fudan University, Shanghai, 200032, China.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: He
authors.affiliation: NPFPC Key Lab of Reproduction Regulation, SIPPR, School of Pharmacy, Fudan University, Shanghai, 200032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.affiliation: NPFPC Key Lab of Reproduction Regulation, SIPPR, School of Pharmacy, Fudan University, Shanghai, 200032, China.
authors.forename: Zhao-Gui
authors.initials: ZG
authors.lastname: Sun
authors.affiliation: NPFPC Key Lab of Reproduction Regulation, SIPPR, School of Pharmacy, Fudan University, Shanghai, 200032, China.
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Shi
authors.affiliation: NPFPC Key Lab of Reproduction Regulation, SIPPR, School of Pharmacy, Fudan University, Shanghai, 200032, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics; D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002824:Chorionic Villi / Q000187:drug effects / Q000378:metabolism; D003656:Decidua / Q000166:cytology / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D010064:Embryo Implantation / Q000187:drug effects / Q000235:genetics*; D004967:Estrogens / Q000494:pharmacology*; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006801:Humans; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D013256:Steroids / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects* / Q000235:genetics; D014599:Uterus / Q000378:metabolism*; D055815:Young Adult
chemical_list: D004967:Estrogens; C527709:Ndrg4 protein, mouse; D009419:Nerve Tissue Proteins; D013256:Steroids