GnRH agonist improves pregnancy outcome in mice with induced adenomyosis by restoring endometrial receptivity

Abstract

Purpose: Adenomyosis has a negative impact on female fertility. GnRH agonist treatment can improve pregnancy outcomes in women with adenomyosis. However, the impact of GnRH agonist upon endometrium receptivity of patients with adenomyosis remains unclear. In this study, endometrial receptivity and pregnancy outcome were investigated using a mouse model of adenomyosis.Materials and methods: Adenomyosis was induced in 12 female ICR mice, neonatally treated with tamoxifen, while another six female mice (control group) received solvent only. At 75 days, the induced adenomyosis group was randomly divided into two groups: an untreated group and a group treated with GnRH agonist (n = 6 each). Sixty days later, the mice were mated and pregnancy outcomes were observed and compared among the three groups (n = 6 each). In a parallel experiment using the same treatment regimes, uterus samples were collected on day 4 of pregnancy for immunohistochemistry, gene (quantitative polymerase chain reaction) and protein expression (Western blot), and scanning electron microscopy analyses.Results: We found that the average live litter size was reduced in the adenomyosis compared with control group (8 ± 0.56 versus 13 ± 0.71; P = 0.03). However, the litter size was signifi¬cantly increased in the treated with GnRH agonist group compared with the untreated group (12 ± 0.35 versus 8 ± 0.56; P = 0.04). The uterine expression levels of Hoxa10, Hoxa11, Lif and integrin b3 mRNA and protein were decreased in the adenomyosis group, and were significantly increased after GnRH agonist treatment. Additionally, pinopodes were reduced in number and poorly developed in mice with induced adenomyosis. However, pinopodes were abundant and well-developed in the GnRH agonist treatment group.Conclusion: Adenomyosis may have an adverse impact on endometrial receptivity and reduce pregnancy outcomes in mice. However, GnRH agonist may improve the pregnancy outcome by partially restoring endometrial receptivity.