title: GnRH analogues may increase endometrial Hoxa10 promoter methylation and affect endometrial receptivity.
abstract: The present study aimed to investigate whether gonadotropin-releasing hormone analogues (GnRH-as), including GnRH agonists and antagonists, affect endometrial homeobox (Hox) a10 DNA methylation during the implantation window in mice. GnRH analogue mouse models were used and were treated with either human menopausal gonadotropin (HMG) and a GnRH agonist or HMG and a GnRH antagonist. Uterus samples were collected 48 h after GnRH analogue treatment or ovulation. Bisulfite sequencing polymerase chain reaction (PCR), quantitative-PCR and western blot analysis were performed to assess Hoxa10 and integrin β3 expression. Scanning electron microscope analyses were conducted to analyze pinopode development. Compared with the natural cycle control mice, mice in the GnRH analogue groups were found to exhibit increased levels of methylation at the Hoxa10 promoter, decreased Hoxa10 mRNA and protein expression and disrupted pinopode development. These findings suggest that GnRH-as may be associated with altered Hoxa10 DNA methylation, thus GnRH-as may affect uterine Hoxa10 expression and endometrial receptivity.
authors.affiliation: Department of Obstetrics and Gynecology, Reproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Reproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Reproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Yuanzhen
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Reproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Teng
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Reproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Xinlan
authors.initials: X
authors.lastname: Qu
mesh_terms: D000818:Animals; D019175:DNA Methylation / Q000187:drug effects*; D004717:Endometrium / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D005260:Female; D015870:Gene Expression; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology*; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000235:genetics*; D039661:Integrin beta3 / Q000235:genetics; D051379:Mice; D011401:Promoter Regions, Genetic
chemical_list: D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; D039661:Integrin beta3; C092119:Hoxa10 protein, mouse; D007987:Gonadotropin-Releasing Hormone