title: Association of controlled ovarian hyperstimulation treatment with down-regulation of key regulators involved in embryonic implantation in mice.
abstract: The debate exists whether or not gonadotropin-releasing hormone (GnRH) analogs used in controlled ovarian hyperstimulation (COH) impair endometrial receptivity. Homeobox A11 (Hoxa11), Meis homeobox 1 (Meis1), cadherin 1 (Cdh1), and catenin beta 1 (Ctnnb1) are well known to be involved in successful implantation. In this study, the endometrial expression of Hoxa11, Meis1, Cdh1, and Ctnnb1 during the peri-implantation period was investigated in an in vitro fertilization (IVF) mouse model by real-time RT-PCR and Western blot to evaluate the relationship between Hoxa11, Meis1, Cdh1, and Ctnnb1 expression and the impact of the COH on endometrial receptivity. The mimic COH protocols included GnRH agonist plus human menopausal gonadotropin (HMG) (GnRH agonist group), GnRH antagonist plus HMG (GnRH antagonist group), and HMG alone (HMG group). The expression levels of Hoxa11, Meis1, Cdh1, and Ctnnb1 mRNA and protein were decreased in all of the COH groups. The expression levels of Hoxa11 and Ctnnb1 were the lowest in the GnRH agonist group, and those of Meis1 and Cdh1 were lower in the GnRH analog groups than the HMG group. There were positive correlations between the expression of Hoxa11 and Ctnnb1, as well as the expression of Meis1 and Cdh1 among all the groups. In conclusion, the COH protocols, particularly with GnRH analogs, suppressed Hoxa11, Meis1, Ctnnb1 and Cdh1 expression, in mouse endometrium during the peri-implantation period. Our data reveal a novel molecular mechanism by which the COH protocols might impair endometrial receptivity.
authors.affiliation: Reproductive Medicine Center, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Min
authors.initials: M
authors.lastname: Xiong
authors.affiliation: Reproductive Medicine Center, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Hanwang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Reproductive Medicine Center, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.affiliation: Reproductive Medicine Center, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jihui
authors.initials: J
authors.lastname: Ai
authors.affiliation: Department of Surgery, Tongji Hospital, Tongji Mediccal College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Reproductive Medicine Center, Huazhong University of Science and Technology, Wuhan, 430030, China. zhu-guijin@sina.com.
authors.forename: Guijin
authors.initials: G
authors.lastname: Zhu
mesh_terms: D000818:Animals; D015536:Down-Regulation / Q000187:drug effects* / Q000235:genetics*; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D006062:Gonadotropins / Q000235:genetics* / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D051379:Mice; D010062:Ovulation Induction / Q000379:methods*
chemical_list: D006062:Gonadotropins; D006727:Hormone Antagonists; D007987:Gonadotropin-Releasing Hormone