Ratchford Ann M, Esguerra Cybill R, Moley Kelle H
Department of Obstetrics and Gynecology, Washington University in St. Louis, St. Louis, Missouri 63110, USA.
Mol Endocrinol. 2008 Dec;22(12):2643-54. doi: 10.1210/me.2007-0495. Epub 2008 Oct 1.
In women, type 1 diabetes is associated with an increased risk of poor prenatal outcomes such as congenital anomalies and early miscarriage. In murine models of type 1 diabetes, impaired oocyte meiotic maturation, abnormal oocyte metabolism, and increased granulosa cell apoptosis have been noted. because gap junction communication is critical for the regulation of oocyte growth and meiotic maturation, we investigated the level of communication between the oocyte and surrounding cumulus cells in a streptozotocin-induced type 1 diabetic B6SJL/F1 mouse model and the expression of gap junction proteins known as connexins. Fluorescence recovery after photobleaching analyses of cumulus cell-enclosed oocytes (CEOs) from diabetic mice showed a 60% decrease in communication as compared with CEOs from nondiabetic mice. Real-time RT-PCR analyses confirmed the presence of Cx26, Cx37, and Cx57 mRNA and revealed a significant decrease in Cx37 mRNA expression in oocytes from diabetic mice compared with nondiabetic mice. Western analyses detected Cx26 expression in CEO but not denuded oocyte (DO) samples, and Cx37 in DO samples. Cx26 protein levels were decreased by 78% in CEOs from diabetic mice, and Cx37 protein levels were decreased 36% in DOs from diabetic mice. This decrease in connexin expression and gap junction communication in CEOs from diabetic mice may be responsible for the impaired oocyte meiotic maturation and poor pregnancy outcomes.
在女性中，1型糖尿病与不良产前结局的风险增加相关，如先天性异常和早期流产。在1型糖尿病的小鼠模型中，已观察到卵母细胞减数分裂成熟受损、卵母细胞代谢异常以及颗粒细胞凋亡增加。由于缝隙连接通讯对于卵母细胞生长和减数分裂成熟的调节至关重要，我们在链脲佐菌素诱导的1型糖尿病B6SJL/F1小鼠模型中研究了卵母细胞与周围卵丘细胞之间的通讯水平以及称为连接蛋白的缝隙连接蛋白的表达。对糖尿病小鼠的卵丘细胞包被卵母细胞（CEO）进行光漂白后荧光恢复分析显示，与非糖尿病小鼠的CEO相比，通讯减少了60%。实时逆转录-聚合酶链反应分析证实存在Cx26、Cx37和Cx57 mRNA，并显示与非糖尿病小鼠相比，糖尿病小鼠卵母细胞中Cx37 mRNA表达显著降低。蛋白质免疫印迹分析在CEO样本中检测到Cx26表达，但在裸卵（DO）样本中未检测到，在DO样本中检测到Cx37。糖尿病小鼠CEO中Cx26蛋白水平降低了78%，糖尿病小鼠DO中Cx37蛋白水平降低了36%。糖尿病小鼠CEO中连接蛋白表达和缝隙连接通讯的这种降低可能是卵母细胞减数分裂成熟受损和妊娠结局不良的原因。
