Morphometric Analysis of Offspring Ovary in Mice Following Oxaliplatin Treatment during Perinatal Period Using Stereology Technique

Moslem Dahmardeh, J. Sadeghinezhad, Z. Tootian, M. Salehnia
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引用次数: 1

Abstract

Background & objectives: Oxaliplatin is a third-generation of platinum drug which is the main therapeutic agent for the treatment of colorectal cancer. Oxaliplatin not only inhibits DNA replication but also transcription and also induces apoptosis or necrosis in cancer cells and rapidly dividing cell lines. Although it is widely used clinically, there is no enough information regarding its effect on ovarian structure. This study was designed to determine morphometric features of 30and 60-day-old offspring ovaries using precise and unbiased stereological technique following administration of oxaliplatin during perinatal period in mice. Methods: In the present experimental study, 32 adult female mice were used for experimental (pre-pregnant, pregnant and lactation) and control groups. Mice were placed in separate cages for mating. Control group received 0.2 ml saline intraperitoneally (IP) during 21 days of prepregnancy, pregnancy and lactation periods. Experimental groups including pre-pregnancy, pregnancy and lactation groups received 3 mg/kg oxaliplatin thrice in a week IP during 21 days before mating, during pregnancy and lactation periods, respectively. At the 30th and 60th postnatal days (PND), the offspring were euthanized and the ovaries from eight offspring in each group were collected for stereological analysis. Results: The results showed that the mean volume oocytes of antral and preantral follicles and also the mean volume of antral follicles were decreased in experimental groups in comparison with the control group in 30 PND offspring (p<0.05). In 60 PND, offspring, the total volume of follicles, mean volume of antral follicles and also mean volume of oocyte of antral follicles in experimental groups showed significant decrease in comparison with the control group (p<0.05). Total volume of ovary, cortical volume and mean volume of preantral follicles decreased in pregnant experimental group compared to control group (p<0.05). Conclusion: The present results demonstrated that oxaliplatin induces adverse effect on the morphometrical features of the ovary following administration during the perinatal period especially in pregnancy time.
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应用体视学技术对奥沙利铂治疗围产期小鼠后代卵巢的形态计量学分析
背景与目的:奥沙利铂是第三代铂类药物,是目前治疗大肠癌的主要药物。奥沙利铂不仅能抑制DNA复制,还能抑制转录,并能诱导癌细胞和快速分裂细胞系的凋亡或坏死。虽然它在临床上被广泛使用,但关于它对卵巢结构的影响还没有足够的信息。本研究的目的是在围产期给予奥沙利铂后,使用精确和无偏体视技术确定30和60日龄小鼠卵巢的形态特征。方法:选用32只成年雌性小鼠作为实验组(孕前、妊娠、哺乳期)和对照组。老鼠被放在单独的笼子里交配。对照组于孕前、妊娠期和哺乳期21 d腹腔注射生理盐水0.2 ml。试验组包括孕前组、妊娠组和哺乳期组,分别于配种前21天、妊娠期和哺乳期,每隔一周给予3次奥沙利铂,剂量为3 mg/kg。在出生后第30天和第60天对子代实施安乐死,每组取8只子代卵巢进行体视学分析。结果:30只PND子代,各实验组的窦前卵泡平均卵母细胞体积及窦前卵泡平均体积均低于对照组(p<0.05)。60 PND时,各试验组子代、卵泡总量、窦卵泡平均体积和窦卵泡平均卵母细胞体积均显著低于对照组(p<0.05)。妊娠试验组卵巢总体积、皮质体积、腔前卵泡平均体积均低于对照组(p<0.05)。结论:奥沙利铂在围产期尤其是妊娠期对卵巢形态特征有不良影响。
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