【摘要】 目的 探讨自发矮小症雌性SD大鼠(short stature rat, SSR)不孕的原因及其致病机理研究。方法 以成年野生型SD雌性大鼠和SSR雌性大鼠为研究对象，采用阴道涂片法观察动情周期变化；采用同期发情超数排卵方法比较促排卵效果；测定卵巢、子宫重量及体重、卵巢、子宫指数；测定血清中AMH、E2、FSH、LH、FSH/LH含量；对卵巢组织进行转录组学测序以分析基因表达差异。结果 SSR雌性大鼠动情周期无异常，SSR雌性大鼠体重显著低于野生型，其卵巢指数和子宫指数显著高于野生型。排卵结果显示，野生型SD大鼠平均排卵数量显著高于SSR雌性不孕大鼠(P<0.001);野生型SD大鼠血清AMH(P<0.01)、E2(P<0.05)水平显著高于SSR雌性不孕大鼠，血清FSH(P<0.01)、LH(P<0.01)及FSH/LH(P<0.05)水平显著低于SSR雌性不孕大鼠，PROG则不显著；转录组测序获得250个差异表达基因，其中有190个上调基因、60个下调基因。GO和KEGG分析结果显示，差异表达基因主要富集在IL-17信号通路(IL-17 signaling pathway)、p53信号通路(p53 signaling pathway)和细胞因子-细胞因子受体相互作用(cytokine-cytokine receptor interaction)等。利用CytoHubba插件的MCC、MNC、EPC和Degree计算法分别筛选前10的重要节点，取交集最后得到9个Hub基因，分别为Cxcl1、Cxcl2、IL1a、IL1b、Cd80、Mmp13、Mmp8、Fgf3、Ptgs2。结论 SSR雌性大鼠不孕可能与卵巢储备功能下降和卵巢低反应有关，同时筛选出Cxcl1、Cxcl2、IL1a、IL1b、Cd80、Mmp13、Mmp8、Fgf3和Ptgs2与不孕相关，为进一步探究不孕机制奠定理论基础。更多还原

【Abstract】 Objective To investigate the causes of infertility and its pathological mechanism in female SD rats with spontaneous dwarfism(short stature rat, SSR). Methods Adult wildtype and SSR female SD rats were used in this study. A vaginal smear was used to observe changes in the motile cycle. Ovulation promotion was compared using the simultaneous estrus supernumerary ovulation method. Ovarian and uterine weight and body weight, and ovarian and uterine indices were measured. AMH, E2, FSH, LH, and FSH/LH levels in serum were measured. Transcriptome sequencing of ovarian tissues was performed to analyze gene expression differences. Results No abnormalities were observed in the estrous cycle of SSR female rats. The body weight of SSR female rats was significantly lower than that of wildtype rats, and their ovarian and uterine indices were significantly higher than that of wildtype rats. The mean number of ovulations was significantly higher in wildtype rats than in SSR female infertile rats(P < 0.001). Serum AMH(P < 0.01) and E2(P < 0.05) levels were significantly higher in wildtype rats than in SSR female infertile rats, and serum levels of FSH, LH, and FSH/LH(P < 0.05) were significantly lower in SSR infertile females than in SSR infertile rats, while PROG showed no significant difference. Transcriptome sequencing yielded 250 differentially expressed genes, including 190 upregulated and 60 downregulated genes. p53 signaling pathway and cytokine-cytokine receptor interaction. The MCC, MNC, EPC, and degree calculations of the CytoHubba plug-in were used to screen the top 10 significant nodes. The intersection was used to finally obtain nine hub genes, namely Cxcl1, Cxcl2, IL1a, IL1b, Cd80, Mmp13, Mmp8, Fgf3, and Ptgs2. ConclusionsInfertility in SSR female rats may be related to a decreased ovarian reserve function and poor ovarian response. Cxcl1, Cxcl2, IL1a, IL1b, Cd80, Mmp13, Mmp8, Fgf3, and Ptgs2 were associated with infertility, laying a theoretical foundation to further explore infertility mechanisms.更多还原