Rodents on a High-Fat Diet Born to Mothers with Gestational Diabetes Exhibited Sex- Specific Lipidomic Changes in Reproductive Organs, Hormonal Imbalances and Insulin Resistance

Abstract

Background: Maternal gestational diabetes mellitus (GDM) and offspring high-fat diet (HFD) have shown to have sex-specific detrimental effects on the health of offspring. Methods: A maternal GDM mice model was established by feeding maternal C57BL/6 mice HFD and then their offspring were exposed to either HFD or low-fat diet. Testes, ovaries, liver and gonadal adipose tissue were collected from offspring at 20 weeks, and their reproductive lipidomic profiles were characterized using gas chromatography-mass spectrometry. Findings: Male offspring following HFD had a substantially elevated body weight. In reproductive organs and hormones, male offspring from GDM mothers had decreased testes weights and testosterone levels, while female offspring from GDM mothers had increased ovary weights and estrogen levels. AKT pathway were increased in the offspring liver and gonadal adipose tissue of those fed with HFD. The fatty acid profiling showed that testes were prone to the effect of maternal GDM, whereas ovarian metabolite profiles were upregulated in maternal GDM and downregulated in offspring following HFD. Eicosapentaenoic acid were attenuated in both maternal serum and offspring testes under the impact of maternal GDM and in offspring following HFD. Interpretation: Maternal GDM and offspring HFD have different metabolic effects on offspring reproductive organs, and PUFAs may protect against detrimental outcomes in offspring such as obesity. Funding: the National Natural Science Foundation of China, The 111 Project, The National Key Research and Development Program of Reproductive Health & Major Birth Defects Control and Prevention, Chongqing Health Commission, Kuanren Talents Programs, and Chongqing Science & Technology Commission. Declaration of Interest: Andi Wang, Xinyang Yu, Zhu Chen, Yinyin Xia, Chang Chen, Hongbo Qi, Philip N. Baker, Richard Saffery, Ting-Li Han and Hua Zhang declare that they have no conflict of interest. Ethical Approval: All WT C57BL/6 mice in this study were purchased from the Model Animal Research Center of Nanjing University. All animal experiments complied with the ARRIVE guidelines and approved by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University (Batch number: 2020-41).