State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Shandong, China.; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Shandong, China.; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Shandong, China.; Shandong Technology Innovation Center for Reproductive Health, Shandong, China.; Shandong Provincial Clinical Research Center for Reproductive Health, Shandong, China.; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.; Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No. 2021RU001), Shandong, China.
National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Shandong, China.; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Shandong, China.; Shandong Technology Innovation Center for Reproductive Health, Shandong, China.; Shandong Provincial Clinical Research Center for Reproductive Health, Shandong, China.; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.; Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No. 2021RU001), Shandong, China.; State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, The Second Hospital, Shandong University, Shandong, China..
Reprod Biomed Online. 2024 Sep;49(3):103992. doi: 10.1016/j.rbmo.2024.103992. Epub 2024 Apr 13.
What is the potential transmission of metabolic phenotype from IVF offspring to the subsequent generation?
An IVF mouse model was established. The F generation mice were produced though IVF or natural mating and the F generation was obtained through the mating of F generation males with normal females. Their metabolic phenotype, including systemic and hepatic glucolipid metabolism, was examined.
It was found that IVF F males exhibited metabolic changes. Compared with the control group, the IVF F generation showed increased body weight, elevated fasting glucose and insulin, and increased serum triglyceride concentrations. IVF F mice also showed an increased expression of hepatic lipogenesis and autophagy genes. Moreover, IVF F males transmitted some metabolic changes to their own male progeny (IVF F) in the absence of a dietary challenge. IVF F mice had increased peri-epididymal and subcutaneous fat and decreased insulin sensitivity. Under the 'second hit' of a high-fat diet, IVF F mice further showed increased hepatic lipid deposition with unaltered autophagy levels.
This research demonstrates the impact of IVF on hepatic glucose-lipid metabolism in two successive generations of offspring, highlighting the need for additional investigation. Enhanced understanding of the mechanisms underlying the transmission of multigenerational effects induced by IVF could potentially lead to the advancement of therapeutic interventions for individuals experiencing infertility.
体外受精后代的代谢表型向后代传递的潜在可能性是什么？
建立了一个 IVF 小鼠模型。通过 IVF 或自然交配产生 F1 代小鼠，通过 F1 代雄性与正常雌性交配获得 F2 代。检查它们的代谢表型，包括全身和肝糖脂代谢。
发现 IVF F1 雄性表现出代谢变化。与对照组相比，IVF F 代体重增加，空腹血糖和胰岛素升高，血清甘油三酯浓度升高。IVF F 代小鼠的肝脂肪生成和自噬基因表达也增加。此外，IVF F 雄性在没有饮食挑战的情况下将一些代谢变化传递给它们自己的雄性后代（IVF F）。IVF F 代小鼠附睾周围和皮下脂肪增加，胰岛素敏感性降低。在高脂肪饮食的“第二次打击”下，IVF F 代小鼠的肝脂质沉积进一步增加，自噬水平不变。
这项研究表明 IVF 对两代后代肝糖脂代谢的影响，强调需要进一步研究。增强对 IVF 诱导的多代效应传递机制的理解，可能为治疗不孕个体提供潜在的治疗干预措施。
