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首页> 外文期刊>Current therapeutic research, clinical and experimental. >In Vivo Evaluation of the Genotoxic Effects of Gonadotropins on Rat Reticulocytes
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In Vivo Evaluation of the Genotoxic Effects of Gonadotropins on Rat Reticulocytes

机译：促性腺激素对大鼠网织细胞的遗传毒性的体内评价

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BACKGROUND: Gonadotropins, as ovulation-inducing drugs, have been used widely to treat infertility. An epidemiologic correlation between infertility therapy and ovarian cancer development has been reported. However, the effect of gonadotropins in the formation of reproductive tract cancers is controversial.OBJECTIVE: The aim of the study was to determine the in vivo genotoxic effects of gonadotropins on rat reticulocytes.METHODS: In this prospective, randomized, controlled study, rats were randomly assigned to 1 of 5 groups. The calculated rat doses of 0.65 human menopausal gonadotropin (hMG), 0.95 hMG, 0.65 follitropin beta (FB), 0.95 FB, or normal saline (control group) were injected, respectively. These calculated rat doses (U/g) are based on average human gonadotropin doses of 150 and 225 IU/d for a 70-kg woman given in 2-mL saline (the control group received 2 mL of saline). Injections were administered once per day for 5 days, followed by 5 days of rest. Each treatment was repeated for 6 estrus cycles in the rats for a total of 12 estrus cycles. Six months after the last day of the 12th cycle, the rats were euthanized. Bone marrow tissues were removed, and pluripotent reticulocyte cells with micronuclei, nuclear buds, and binuclear abnormalities were analyzed using an in situ micronuclei assay under light microscopy. The proportion of micro-nucleated cells, cells with anaphase bridge, nuclear buds, and other nuclear abnormalities were measured.RESULTS: The number of cells with nuclear buds and binuclear abnormalities in the hMG 225 and FB 225 groups was significantly higher (P < 0.05) than that from the hMG 150, FB 150, and control groups in the cytogenetic analysis of bone marrow stem cells. An increased rate of genotoxicity in all gonadotropin groups versus that of placebo was found.CONCLUSION: In rats, the micronucleus genotoxicity assay suggests a dose-dependent gonadotropin effect on genomic instability in bone marrow stem cells in vivo.
机译：背景：促性腺激素作为促排卵药已被广泛用于治疗不孕症。据报道，不育治疗与卵巢癌发展之间存在流行病学相关性。然而，促性腺激素在生殖道癌症形成中的作用是有争议的。目的：本研究的目的是确定促性腺激素对大鼠网织红细胞的体内遗传毒性。方法：在这项前瞻性，随机对照研究中，对大鼠进行了研究。随机分配给5组中的1组。分别注射计算得出的大鼠剂量的0.65人更年期促性腺激素（hMG），0.95 hMG，0.65促卵泡素β（FB），0.95 FB或生理盐水（对照组）。这些计算的大鼠剂量（U / g）是基于70公斤的女性在2 mL生理盐水中（对照组接受2 mL生理盐水）得出的人促性腺激素平均剂量150和225 IU / d。每天注射一次，持续5天，然后休息5天。在大鼠中，每种治疗重复6个发情周期，总共12个发情周期。在第十二个周期的最后一天六个月后，对大鼠实施安乐死。去除骨髓组织，并在光学显微镜下使用原位微核分析法分析具有微核，核芽和双核异常的多能网织红细胞。结果：hMG 225和FB 225组中有核芽和双核异常的细胞数量明显增加（P <0.05） ）较hMG 150，FB 150和对照组在骨髓干细胞的细胞遗传学分析中得到的结果更高。结论：在所有大鼠中，促性腺激素组的遗传毒性率均高于安慰剂组。结论：在大鼠中，微核遗传毒性试验表明，剂量依赖性促性腺激素对体内骨髓干细胞基因组不稳定的作用。

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