Ahmed R G, Incerpi S
Division of Anatomy and Embryology, Zoology Department, Faculty of Science, Beni-Suef University, Egypt.
Int J Dev Neurosci. 2013 Apr;31(2):96-104. doi: 10.1016/j.ijdevneu.2012.11.005. Epub 2012 Nov 23.
Administration of chemotherapy during pregnancy may represent a big risk factor for the developing brain, therefore we studied whether the transplacental transport of doxorubicin (DOX) may affect the development of neuroendocrine system. DOX (25 mg/kg; 3 times interaperitoneally/week) was given to pregnant rats during whole gestation period. The disturbances in neuroendocrine functions were investigated at gestation day (GD) 15 and 20 by following the maternal and fetal thyroid hormone levels, fetal nucleotides (ATP, ADP, AMP) levels and adenosine triphosphatase (Na(+), K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase) activities in two brain regions, cerebrum and cerebellum. In control group, the levels of maternal and fetal serum thyroxine (T4), triiodothyronine (T3), thyrotropin (TSH), and fetal serum growth hormone (GH) increased from days 15 to 20, whereas in the DOX group, a decrease in maternal and fetal T4, T3 and increase in TSH levels (hypothyroid status) were observed. Also, the levels of fetal GH decreased continuously from GD 15 to 20 with respect to control group. In cerebrum and cerebellum, the levels of fetal nucleotides and the activities of fetal ATPases in control group followed a synchronized course of development. The fetal hypothyroidism due to maternal administration of DOX decreased the levels of nucleotides, ATPases activities, and total adenylate, instead, the adenylate energy charge showed a trend to an increase in both brain regions at all ages tested. These alterations were dose- and age-dependent and this, in turn, may impair the nerve transmission. Finally, DOX may act as neuroendocrine disruptor causing hypothyroidism and fetal brain energetic dysfunction.
孕期进行化疗可能是发育中大脑的一个重大风险因素，因此我们研究了阿霉素（DOX）的经胎盘转运是否会影响神经内分泌系统的发育。在整个妊娠期给怀孕大鼠注射DOX（25毫克/千克；每周腹腔注射3次）。在妊娠第15天和第20天，通过检测母体和胎儿的甲状腺激素水平、胎儿核苷酸（ATP、ADP、AMP）水平以及大脑两个区域（大脑和小脑）的腺苷三磷酸酶（Na(+)、K(+)-ATP酶、Ca(2+)-ATP酶和Mg(2+)-ATP酶）活性，来研究神经内分泌功能的紊乱情况。在对照组中，母体和胎儿血清甲状腺素（T4）、三碘甲状腺原氨酸（T3）、促甲状腺激素（TSH）以及胎儿血清生长激素（GH）的水平从第15天到第20天有所升高，而在DOX组中，观察到母体和胎儿的T4、T3水平下降以及TSH水平升高（甲状腺功能减退状态）。此外，与对照组相比，胎儿GH的水平从妊娠第15天到第20天持续下降。在大脑和小脑中，对照组胎儿核苷酸水平和胎儿ATP酶活性遵循同步的发育过程。母体注射DOX导致的胎儿甲状腺功能减退降低了核苷酸水平、ATP酶活性和总腺苷酸，相反，在所有测试年龄段，两个脑区的腺苷酸能量电荷均呈现升高趋势。这些改变具有剂量和年龄依赖性，进而可能损害神经传递。最后，DOX可能作为神经内分泌干扰物导致甲状腺功能减退和胎儿脑能量功能障碍。
