Guo Song, Lu Xiaowei, Gu Ruihuan, Zhang Di, Sun Yijuan, Feng Yun
Department of Obstetrics and Gynecology, Reproductive Medicine Center, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Gynecology, Shanghai Ji Ai Genetics & In Vitro Fertilization Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, People's Republic of China.
Drug Des Devel Ther. 2017 Mar 9;11:695-704. doi: 10.2147/DDDT.S127889. eCollection 2017.
Adenomyosis is a common, benign gynecological condition of the female reproductive tract characterized by heavy menstrual bleeding and dysmenorrhea. Gonadotropin-releasing hormone (GnRH) agonists are one of the medications used in adenomyosis treatment; however, their underlying mechanisms are poorly understood. Moreover, it is difficult to obtain endometrial samples from women undergoing such treatment. To overcome this, we generated an adenomyosis mouse model, which we treated with an GnRH agonist to determine its effect on pregnancy outcomes. We also analyzed endometrial gene expression following GnRH agonist treatment to determine the mechanisms that may affect pregnancy outcome in individuals with adenomyosis.
Neonatal female mice were divided into a control group, an untreated adenomyosis group, and an adenomyosis group treated with a GnRH agonist (n=6 each). The pregnancy outcome was observed and compared among the groups. Then, three randomly chosen transcriptomes from endometrial tissues from day 4 of pregnancy were analyzed between the adenomyosis group and the GnRH agonist treatment group by RNA sequencing and quantitative reverse transcription polymerase chain reaction (PCR).
The litter size was significantly smaller in the adenomyosis group than in the control group (7±0.28 vs 11±0.26; <0.05). However, the average live litter size was increased (10±0.28 vs 7±0.28; <0.05) after GnRH agonist treatment. Three hundred and fifty-nine genes were differentially expressed in the GnRH agonist-treated group compared with the untreated group (218 were downregulated and 141 were upregulated). Differentially expressed genes were related to diverse biological processes, including estrogen metabolism, cell cycle, and metabolite biosynthesis.
GnRH agonist treatment appears to improve the pregnancy outcome of adenomyosis in a mouse model. Besides pituitary down-regulation, other possible mechanisms such as the regulation of cell proliferation may play a role in this. These new insights into GnRH agonist mechanisms will be useful for future adenomyosis treatment.
子宫腺肌病是女性生殖道常见的良性妇科疾病，其特征为月经过多和痛经。促性腺激素释放激素（GnRH）激动剂是用于治疗子宫腺肌病的药物之一；然而，其潜在机制尚不清楚。此外，从接受此类治疗的女性中获取子宫内膜样本很困难。为克服这一问题，我们构建了子宫腺肌病小鼠模型，用GnRH激动剂对其进行治疗以确定其对妊娠结局的影响。我们还分析了GnRH激动剂治疗后子宫内膜基因表达，以确定可能影响子宫腺肌病患者妊娠结局的机制。
将新生雌性小鼠分为对照组、未治疗的子宫腺肌病组和用GnRH激动剂治疗的子宫腺肌病组（每组n = 6）。观察并比较各组的妊娠结局。然后，通过RNA测序和定量逆转录聚合酶链反应（PCR）分析妊娠第4天子宫腺肌病组和GnRH激动剂治疗组中随机选择的三个子宫内膜组织转录组。
子宫腺肌病组的窝仔数显著低于对照组（7±0.28对11±0.26；P<0.05）。然而，GnRH激动剂治疗后平均存活窝仔数增加（10±0.28对7±0.28；P<0.05）。与未治疗组相比，GnRH激动剂治疗组有359个基因差异表达（218个下调，141个上调）。差异表达基因与多种生物学过程相关，包括雌激素代谢、细胞周期和代谢物生物合成。
在小鼠模型中，GnRH激动剂治疗似乎可改善子宫腺肌病的妊娠结局。除了垂体下调外，其他可能的机制如细胞增殖调节可能也起作用。这些关于GnRH激动剂机制的新见解将有助于未来子宫腺肌病的治疗。
