Reproductive Medical Center, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, P.R. China.
Mol Med Rep. 2017 Oct;16(4):5189-5194. doi: 10.3892/mmr.2017.7245. Epub 2017 Aug 14.
Gestational diabetes mellitus (GDM) is characterized by an initial diagnosis of glucose intolerance during pregnancy. There is increasing evidence supporting the association between GDM and the inhibited development of several organs in offspring. In the present study, a murine GDM model was established in mice by intraperitoneal injection of streptozotocin to evaluate the effect of maternal diabetes on the initiation of meiosis in female germ cells of offspring. The effect of GDM on the initiation of meiosis in the offspring was evaluated by reverse transcription-quantitative polymerase chain reaction, flow cytometry and hematoxylin and eosin staining. The results showed that, compared with the control group, fetal ovary growth was inhibited, the expression levels of meiosis‑specific genes, stimulated by retinoic acid gene 8, synaptonemal complex protein, and DNA meiotic recombinase were inhibited, and the number of primordial/primary follicles was reduced in the GDM group. These may have been induced by an increase of apoptosis and inhibition of growth, as the mRNA levels of p21, a vital G1 cell cycle inhibitor, and apoptotic genes were upregulated, whereas the expression levels of genes important in folliculogenesis were decreased in the GDM group. In conclusion, the data obtained in the present study suggested that maternal diabetes may impair the initiation of meiosis and ovarian growth via growth inhibition, cell cycle arrest and the induction of apoptosis.
妊娠期糖尿病(GDM)的特征是在怀孕期间初次诊断为葡萄糖耐量异常。越来越多的证据支持 GDM 与后代几种器官发育受阻之间存在关联。在本研究中,通过腹腔注射链脲佐菌素在小鼠中建立了 GDM 模型,以评估母体糖尿病对后代生殖细胞减数分裂起始的影响。通过逆转录定量聚合酶链反应、流式细胞术和苏木精-伊红染色评估 GDM 对后代减数分裂起始的影响。结果显示,与对照组相比,GDM 组胎儿卵巢生长受到抑制,减数分裂特异性基因、维甲酸诱导基因 8、联会复合体蛋白和 DNA 减数分裂重组酶的表达水平受到抑制,原始/初级卵泡数量减少。这可能是由于细胞凋亡增加和生长抑制引起的,因为细胞周期抑制剂 p21 和凋亡基因的 mRNA 水平上调,而卵泡发生过程中重要基因的表达水平下调。综上所述,本研究数据表明,母体糖尿病可能通过生长抑制、细胞周期停滞和诱导细胞凋亡来损害减数分裂和卵巢生长的启动。