Effects of GnRH antagonist on endometrial protein profiles in the window of implantation

Abstract

GnRH antagonists can suppress luteinizing hormone and follicle-stimulating hormone (FSH), with less initial stimulatory effect and lower risk of ovarian hyperstimulation syndrome. The effects of GnRH antagonists on embryonic implantation remain controversial. To evaluate the effects of GnRH antagonists, endometrial tissues were biopsied from 12 women with intracytoplasmic sperm injection treatment, in which four subjects undergoing controlled ovulation stimulation with rFSH and GnRH antagonist, four subjects with a GnRH agonist long protocol, and four natural cycle controls. After iTRAQ quantification analysis, 24 proteins showed differential expression between natural cycle and agonist treatment group and 39 proteins between natural cycle and antagonist treatment group. A total of seven proteins demonstrated differential expression only in antagonist treatment group. Bioinformatic analysis implied these proteins can function in cell processes including angiogenesis, cell proliferation, apoptosis, cell migration, and immune response. Furthermore, GnRH antagonist suppressed the function of GNAS and ANPEP, which were important for endometrial functions. Immunohistochemical staining showed that ANPEP was mainly localized in the human endometrial stroma, while ACO2, CDC5L, and GNAS were mainly localized in the glands. This study could provide insights into the effect of GnRH antagonists on the endometrium, and help optimize the embryo implantation and improve the success rate for GnRH antagonist protocol.

Increased Uterine NK cell numbers and perforin expression during the implantation phase in IVF Cycles with GnRH Antagonist Protocol

“…Thus far, no significant differences have been found between the two protocols with respect to the levels of specific biomarkers in follicular fluid, oocyte dysmorphisms, oocyte quality, and embryo quality8910. This indicates that endometrial receptivity, but not embryo quality, may be a factor contributing to the low pregnancy rates observed in patients treated with GnRH antagonist11. Recent findings have shown that the luteal phase single-dose GnRH agonist protocol can improve clinical outcomes after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), suggesting that the GnRH agonist may exert beneficial effects on the endometrium as endometrial epithelial and stromal cells express GnRH receptors (GnRHRs)1213.…”

Serum proteomic-based analysis by iTRAQ of damp-heat impeding syndrome of rheumatoid arthritis

“…Five top significant canonical pathways are displayed along the xaxis. The threshold line corresponds to a P value of 0.05 [25]. All shown pathways are superior to the threshold [26].…”

“…For the ratio, taller bars have more proteins associated with the Canonical Pathway than shorter bars. The graph displaying the various pathways is presented from largest ratio to smallest ratio [25].…”

“…Relative protein abundance ratios between the two groups were calculated from iTRAQ reagent reporter ion intensities from higher energy collisional dissociation spectra using the algorithm similar to Libra [25]. Mean and standard deviation for each protein across subjects was calculated.…”

The Use of Proteomics in Assisted Reproduction

“…Seven proteins, including ACO2, CDC5L, GNAS, ARF1, ANPEP, SERPIND1 and SEC23B were differentially expressed exclusively in the GnRH antagonist group. According to the subsequent bioinformatic analysis, these proteins are mainly involved in angiogenesis, cell cycle, apoptosis, cell migration, cell proliferation and immune response (117).…”