Abstract：
OBJECTIVE: What is the potential transmission of metabolic phenotype from IVF offspring to the subsequent generation?
METHODS: An IVF mouse model was established. The F1 generation mice were produced though IVF or natural mating and the F2 generation was obtained through the mating of F1 generation males with normal females. Their metabolic phenotype, including systemic and hepatic glucolipid metabolism, was examined.
RESULTS: It was found that IVF F1 males exhibited metabolic changes. Compared with the control group, the IVF F1 generation showed increased body weight, elevated fasting glucose and insulin, and increased serum triglyceride concentrations. IVF F1 mice also showed an increased expression of hepatic lipogenesis and autophagy genes. Moreover, IVF F1 males transmitted some metabolic changes to their own male progeny (IVF F2) in the absence of a dietary challenge. IVF F2 mice had increased peri-epididymal and subcutaneous fat and decreased insulin sensitivity. Under the \'second hit\' of a high-fat diet, IVF F2 mice further showed increased hepatic lipid deposition with unaltered autophagy levels.
CONCLUSIONS: 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.
METHODS: An IVF mouse model was established. The F1 generation mice were produced though IVF or natural mating and the F2 generation was obtained through the mating of F1 generation males with normal females. Their metabolic phenotype, including systemic and hepatic glucolipid metabolism, was examined.
RESULTS: It was found that IVF F1 males exhibited metabolic changes. Compared with the control group, the IVF F1 generation showed increased body weight, elevated fasting glucose and insulin, and increased serum triglyceride concentrations. IVF F1 mice also showed an increased expression of hepatic lipogenesis and autophagy genes. Moreover, IVF F1 males transmitted some metabolic changes to their own male progeny (IVF F2) in the absence of a dietary challenge. IVF F2 mice had increased peri-epididymal and subcutaneous fat and decreased insulin sensitivity. Under the \'second hit\' of a high-fat diet, IVF F2 mice further showed increased hepatic lipid deposition with unaltered autophagy levels.
CONCLUSIONS: 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.
摘要：
目的：从IVF后代到后代的代谢表型的潜在传递是什么？
方法：建立了IVF小鼠模型。通过IVF或自然交配产生F1代小鼠，并通过F1代雄性与正常雌性交配获得F2代小鼠。他们的代谢表型，包括全身和肝脏糖脂代谢，被检查过。
结果：发现IVFF1男性表现出代谢变化。与对照组相比,IVFF1一代显示体重增加，空腹血糖和胰岛素升高，和增加血清甘油三酯浓度。IVFF1小鼠还显示肝脏脂肪生成和自噬基因的表达增加。此外，在没有饮食挑战的情况下，IVFF1雄性将一些代谢变化传递给自己的雄性后代（IVFF2）。IVFF2小鼠的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，IVFF2小鼠进一步显示肝脏脂质沉积增加，自噬水平未改变。
结论：这项研究证明了IVF对连续两代后代肝脏糖脂代谢的影响，强调需要进一步调查。增强对IVF引起的多代效应传递的潜在机制的理解可能会导致对经历不孕症的个体的治疗干预措施的进步。
方法：建立了IVF小鼠模型。通过IVF或自然交配产生F1代小鼠，并通过F1代雄性与正常雌性交配获得F2代小鼠。他们的代谢表型，包括全身和肝脏糖脂代谢，被检查过。
结果：发现IVFF1男性表现出代谢变化。与对照组相比,IVFF1一代显示体重增加，空腹血糖和胰岛素升高，和增加血清甘油三酯浓度。IVFF1小鼠还显示肝脏脂肪生成和自噬基因的表达增加。此外，在没有饮食挑战的情况下，IVFF1雄性将一些代谢变化传递给自己的雄性后代（IVFF2）。IVFF2小鼠的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，IVFF2小鼠进一步显示肝脏脂质沉积增加，自噬水平未改变。
结论：这项研究证明了IVF对连续两代后代肝脏糖脂代谢的影响，强调需要进一步调查。增强对IVF引起的多代效应传递的潜在机制的理解可能会导致对经历不孕症的个体的治疗干预措施的进步。
