Intergenerational Hyperglycemia Impairs Mitochondrial Function and Follicular Development and Causes Oxidative Stress in Rat Ovaries Independent of the Consumption of a High-Fat Diet

• Published in: Nutrients 2023-10, Vol.15 (20), p.4407
• Main Authors: Paula, Verônyca Gonçalves, Sinzato, Yuri Karen, Gallego, Franciane Quintanilha, Cruz, Larissa Lopes, Aquino, Ariana Musa de, Scarano, Wellerson Rodrigo, Corrente, José Eduardo, Volpato, Gustavo Tadeu, Damasceno, Débora Cristina
• Format: Article
• Language: English
• Subjects: Apoptosis; Cell growth; Diabetes; Diabetes therapy; Diet; Females; Fertility; Follicles; Glucose; Glucose tolerance tests; high-fat diet; Hormones; Hyperglycemia; Infertility; Insulin resistance; Kinases; Laboratory animals; Males; Mitochondria; Ovaries; ovary; Oxidative stress; Pregnancy; Process controls; Progesterone; Proteins; rats; Vagina; Weaning; Womens health
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu15204407

We analyzed the influence of maternal hyperglycemia and the post-weaning consumption of a high-fat diet on the mitochondrial function and ovarian development of the adult pups of diabetic rats. Female rats received citrate buffer (Control–C) or Streptozotocin (for diabetes induction–D) on postnatal day 5. These adult rats were mated to obtain female pups (O) from control dams (OC) or from diabetic dams (OD), and they received a standard diet (SD) or high-fat diet (HFD) from weaning to adulthood and were distributed into OC/SD, OC/HFD, OD/SD, and OD/HFD. In adulthood, the OGTT and AUC were performed. These rats were anesthetized and euthanized for sample collection. A high percentage of diabetic rats were found to be in the OD/HFD group (OD/HFD 40% vs. OC/SD 0% p < 0.05). Progesterone concentrations were lower in the experimental groups (OC/HFD 0.40 ± 0.04; OD/SD 0.30 ± 0.03; OD/HFD 0.24 ± 0.04 vs. OC/SD 0.45 ± 0.03 p < 0.0001). There was a lower expression of MFF (OD/SD 0.34 ± 0.33; OD/HFD 0.29 ± 0.2 vs. OC/SD 1.0 ± 0.41 p = 0.0015) and MFN2 in the OD/SD and OD/HFD groups (OD/SD 0.41 ± 0.21; OD/HFD 0.77 ± 0.18 vs. OC/SD 1.0 ± 0.45 p = 0.0037). The number of follicles was lower in the OD/SD and OD/HFD groups. A lower staining intensity for SOD and Catalase and higher staining intensity for MDA were found in ovarian cells in the OC/HFD, OD/SD, and OD/HFD groups. Fetal programming was responsible for mitochondrial dysfunction, ovarian reserve loss, and oxidative stress; the association of maternal diabetes with an HFD was responsible for the higher occurrence of diabetes in female adult pups.