title: Increased Uterine NK cell numbers and perforin expression during the implantation phase in IVF Cycles with GnRH Antagonist Protocol.
abstract: GnRH antagonist negatively affects endometrial receptivity in in vitro fertilization (IVF) cycles, however, its underlying mechanism remains unclear. To explore its target molecules, we studied endometria in the window phase of fixed GnRH antagonist, low-dose flexible GnRH antagonist, GnRH agonist long protocol, and untreated control groups. There were 384 differentially expressed genes (DEGs) in the fixed antagonist group with greater than twofold expression change compared with the control group and 197 DEGs between the fixed antagonist and agonist groups, the majority of which were associated with the natural killer (NK) cell-mediated cytotoxicity pathway. We then analysed the PRF1 and FASLG protein levels. The perforin level were significantly higher in both the antagonist groups than in other two groups, and was higher in the fixed antagonist group. Similarly, the uNK cell numbers were higher in the antagonist groups, and the highest uNK cell number occurred in the fixed group (p < 0.05). No significant differences existed in the Fas ligand levels and apoptosis rates among the three treatment groups, but were higher in the treatment groups than the control group. Together, these data indicate that GnRH antagonist may increase the uNK cell numbers and perforin expression, and this effect may be dose-dependent.
authors.affiliation: Reproductive Medical Center of Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Bufang
authors.initials: B
authors.lastname: Xu
authors.affiliation: Reproductive Medical Center of Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Wang
authors.affiliation: Reproductive Medical Center of Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Xia
authors.affiliation: Reproductive Medical Center of Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Reproductive Medical Center of Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Wu
authors.affiliation: Reproductive Medical Center of Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.|Shanghai Key Laboratory of Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Aijun
authors.initials: A
authors.lastname: Zhang
mesh_terms: D000328:Adult; D019002:CD56 Antigen / Q000235:genetics / Q000378:metabolism; D010064:Embryo Implantation; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000378:metabolism; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D005260:Female; D005307:Fertilization in Vitro; D005640:Follicle Stimulating Hormone / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D054353:Perforin / Q000235:genetics / Q000378:metabolism*; D025341:Principal Component Analysis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D017329:Triptorelin Pamoate / Q000494:pharmacology; D014599:Uterus / Q000166:cytology
chemical_list: D019002:CD56 Antigen; D053222:Fas Ligand Protein; D011994:Recombinant Proteins; D017329:Triptorelin Pamoate; D054353:Perforin; D007987:Gonadotropin-Releasing Hormone; D005640:Follicle Stimulating Hormone