IVF exposure induced intergenerational effects on metabolic phenotype in mice.

Reprod Biomed Online

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.. Electronic address:

Published: September 2024

Research Question: What is the potential transmission of metabolic phenotype from IVF offspring to the subsequent generation?

Design: 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.

Results: 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.

Conclusion: 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.

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http://dx.doi.org/10.1016/j.rbmo.2024.103992DOI Listing

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