Bueno Aline, Sinzato Yuri Karen, Sudano Mateus José, Alvarenga Fernanda da Cruz Landim E, Calderon Iracema de Mattos Paranhos, Rudge Marilza Vieira Cunha, Damasceno Débora Cristina
Laboratory of Experimental Research on Gynecology and Obstetrics, Department of Gynecology and Obstetrics, Botucatu Medical School, Univ Estadual Paulista - UNESP, Botucatu, São Paulo, Brazil.
Diabetes Metab Res Rev. 2014 Oct;30(7):575-81. doi: 10.1002/dmrr.2521.
Diabetic pregnancy have increased rates of congenital malformation and neonatal mortality. In vitro studies suggest hyperglycemia associated with diabetes impair embryogenesis but in vivo investigations on maternal hyperglycemic insult and early embryo development are scarce. We evaluated the embryofetal development on experimental diabetes models to assess whether hyperglycemia at preimplantation period impairs the progression of pregnancy.
Different hyperglycemic intensities were obtained by two experimental diabetes models. Female Sprague Dawley rats received streptozotocin at birth (mild diabetes) or at day 90 of life (severe diabetes). For both diabetic groups hyperglycemia was confirmed 5 days after diabetes induction and the mating was performed around 100 day of life. For preimplantation analysis, embryos were recovered at D4 of pregnancy. Another group of animals was submitted to laparotomy at D21 to assess contents of the uterus and fetal viability.
Mild (i) and Severe (ii) diabetes modified the early development. Degenerating embryos percentage was higher compared to control (11%) (i) 30.7%, (ii) 37.3%. Cell number mean dropped according to hyperglycemic intensity (control 30.57, (i) 21.42, (ii) 13.42). Pre and post-implantation loss rates were higher in diabetic groups. The fetal viability also decreased from 96% in the control group to (i) 78.7% and (ii) 80.6%.
Our results show that during diabetic pregnancy, preimplantation embryos present decreased cell number due to higher apoptosis rates, which are dependent of the hyperglycemic intensity. Moreover, fetal viability was also decreased suggesting that the quality of these embryos at long-term may be questioned.
糖尿病妊娠时先天性畸形和新生儿死亡率增加。体外研究表明,与糖尿病相关的高血糖会损害胚胎发育,但关于母体高血糖损伤和早期胚胎发育的体内研究较少。我们在实验性糖尿病模型上评估胚胎-胎儿发育,以评估植入前期的高血糖是否会损害妊娠进程。
通过两种实验性糖尿病模型获得不同的高血糖强度。雌性斯普拉格-道利大鼠在出生时(轻度糖尿病)或出生后第90天(重度糖尿病)接受链脲佐菌素。对于两个糖尿病组,在诱导糖尿病后5天确认高血糖,并在出生后约100天进行交配。为了进行植入前分析,在妊娠第4天回收胚胎。另一组动物在第21天接受剖腹手术,以评估子宫内容物和胎儿活力。
轻度(i)和重度(ii)糖尿病改变了早期发育。与对照组(11%)相比,退化胚胎的百分比更高(i)30.7%,(ii)37.3%。细胞数量平均值根据高血糖强度下降(对照组30.57,(i)21.42,(ii)13.42)。糖尿病组植入前和植入后的损失率更高。胎儿存活率也从对照组的96%降至(i)78.7%和(ii)80.6%。
我们的结果表明,在糖尿病妊娠期间,植入前胚胎由于凋亡率较高而细胞数量减少,这取决于高血糖强度。此外,胎儿存活率也降低,表明这些胚胎的长期质量可能受到质疑。