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Risk and mechanism of glucose metabolism disorder in the offspring conceived by female fertility maintenance technology
Cryobiology ( IF 2.3 ) Pub Date : 2020-10-01 , DOI: 10.1016/j.cryobiol.2020.08.001
Xue Zhou 1 , Bei Yan 2 , Xian Xu 3 , Xiao-Li Yu 3 , Xu-Feng Fu 3 , Yu-Fang Cai 3 , Yan-Yan Xu 3 , Yun-Ge Tang 4 , Xin-Zong Zhang 4 , Hong-Yan Wang 2
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Although female fertility maintenance technology (FFMT) provides an effective option for preserving fertility in patients with cancer suffering from fertility loss due to cancer treatment, previous studies have shown that the technique has certain potential risks and requires an assessment of the health status of the offspring since FFMT may lead to glucose metabolism disorder in offspring mice. The present animal study examined the glucose metabolism of adult mice offspring born from ovarian tissue cryopreservation and orthotopic allotransplantation. The mice were divided into three groups: normal, fresh ovary transplantation, and cryopreserved ovary transplantation. We recorded fasting blood glucose, glucose tolerance, and fasting serum insulin level for six months. Liver DNA, RNA, and proteins were extracted to detect the interaction between DNA methylation and Grb10 expression and insulin signaling pathway factors such as P-IGF1R, P-IRS2, P-AKT, and Grb10. Female recipient mice that received FFMT could successfully give birth after mating. The average litter size and total litter size of the cryopreserved and fresh groups showed marked differences compared with the normal group. Compared with the normal group, the fasting blood glucose and fasting serum insulin levels were higher in the cryopreserved and fresh groups. The mRNA and protein expressions of Grb10 were higher in the fresh and cryopreserved groups. Compared with the normal group, the DNA methylation status of four of the 11 sites of the Grb10 promoter was lower in the cryopreserved group. Grb10 overexpression inhibited the downstream phosphorylation protein factor expression (p-IGF-1R, p-IRS2, and p-Akt) of the IGF-1R signaling pathway. Female fertility maintenance technology (FFMT), including ovarian tissue cryopreservation (OTC), and orthotopic allotransplantation techniques might lead to glucose metabolism disorders in offspring mice.

中文翻译:

女性生育维持技术孕育后代糖代谢紊乱的风险及机制

尽管女性生育力维持技术(FFMT)为因癌症治疗导致生育能力丧失的癌症患者保留生育能力提供了有效的选择,但之前的研究表明该技术具有一定的潜在风险,需要对后代的健康状况进行评估。因为FFMT可能导致后代小鼠的糖代谢紊乱。本动物研究检查了从卵巢组织冷冻保存和原位同种异体移植出生的成年小鼠后代的葡萄糖代谢。将小鼠分为三组:正常、新鲜卵巢移植和冷冻卵巢移植。我们记录了六个月的空腹血糖、葡萄糖耐量和空腹血清胰岛素水平。肝脏 DNA、RNA、并提取蛋白质以检测DNA甲基化与Grb10表达与胰岛素信号通路因子如P-IGF1R、P-IRS2、P-AKT和Grb10之间的相互作用。接受 FFMT 的雌性受体小鼠在交配后可以成功分娩。与正常组相比,冷冻组和新鲜组的平均窝产仔数和总窝产仔数显示出显着差异。与正常组相比,冷冻组和新鲜组的空腹血糖和空腹血清胰岛素水平较高。Grb10的mRNA和蛋白表达在新鲜组和冷冻组中均较高。与正常组相比,冷冻保存组 Grb10 启动子 11 个位点中的 4 个位点的 DNA 甲基化状态较低。Grb10 过表达抑制了 IGF-1R 信号通路的下游磷酸化蛋白因子表达(p-IGF-1R、p-IRS2 和 p-Akt)。女性生育力维持技术 (FFMT),包括卵巢组织冷冻保存 (OTC) 和原位同种异体移植技术,可能会导致后代小鼠的葡萄糖代谢紊乱。
更新日期:2020-10-01
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