(194) The Impact of Diet-Induced Obesity on Maternal Metabolism and Reproductive Function

Sameeksha Bhaye¹, Kassandra Sandoval², Chanaka Rabel¹, Malia D. Berg¹, Bruce Southey¹, Kelly S. Swanson^1,2 and Matthew Dean^1,2

¹ Department of Animal Sciences, College of Agricultural, Consumer and Environmental Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA
² Division of Nutritional Sciences, College of Agricultural, Consumer and Environmental Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA

Abstract Text:

Obesity is a common metabolic disorder associated with diabetes mellitus, cardiovascular disorders, and reduced fertility. It has a wide impact on both males and females. In females, obesity is related to menstrual disorders, anovulation, miscarriage, and infertility. Studies have shown that women with a high body mass index undergoing IVF had lower implantation and live birth rates. However, findings from diet-induced obese (DIO) mouse models are inconsistent, and many do not report a decline in fertility as observed in women. Additionally, many studies fail to characterize the metabolic phenotype in their DIO mouse model. Consequently, the link between obesity and fertility is elusive. Therefore, this study aimed to determine the effect of two high-fat diets on systemic metabolism and reproductive function relative to a low-fat diet in mice. Eight-week-old mice (n=64) were randomly divided into three groups and fed 10% kcal from fat (low-fat diet [LFD]), 45% kcal from fat (high-fat diet [HFD]), or 60% kcal from fat (very high-fat diet [VHFD]) for 18 weeks. Percent kcal energy from carbohydrates was adjusted based on the fat kcal percentage while keeping other components consistent. In the 18^th week, some mice were sacrificed in proestrus after fasting for 5-6 hours. To assess the metabolic dysfunction liver glycogen and triglyceride concentration were determined. Also, serum was analyzed for metabolites, reproductive hormones and subjected to intraperitoneal glucose tolerance tests in weeks 5,10, and 15. A significant increase in body weight was observed by the 9^th week of feeding in both high-fat diet groups. Additionally, mice from these groups had a higher adiposity index. Liver glycogen level was reduced in both high-fat diet groups, while liver triglyceride level increased in the VHFD group. The VHFD group showed reduced glucose tolerance from week 5, whereas the HFD group showed reduced tolerance in weeks 10 and 15. Serum metabolites analysis revealed that serum cholesterol was increased in both high-fat diet groups, while serum glycerol-3-phosphate was only increased in the VHFD group. Few metabolites were identified only in the high-fat diet groups. There was no difference in estrous cycle length among the groups. The ovary weight was reduced, whereas uterine weight remained unaffected in HFD and VHFD groups compared to the control. Serum testosterone concentration was reduced, and serum LH concentration was increased in the VHFD group. However, there was no difference in progesterone or FSH concentrations, and estradiol was undetectable. The LH/FSH ratio did not differ between groups. Other mice were housed with male mice for 60 days to assess fertility. The day a vaginal plug was found in the mouse was considered 0.5 days post coitum (DPC) and mice were sacrificed at 18.5 DPC. Mice were considered infertile if a vaginal plug was not observed after 60 days of housing with a male. VHFD group showed a 60% reduction in fertility. Litter size increased by 40% in the HFD group. Fetal mass, placental mass, and placental efficiency were unaffected by HFD or VHFD. In brief, 60% kcal from fat resulted in the greatest metabolic disturbance, reduced fertility, and mimicked some features observed in obese women. Further study will investigate how obesity affects ovarian and uterine morphology and functioning.

Keywords: Diet-Induced Obesity, Fertility, Adiposity, IPGTT, Placental Efficiency, Reproductive Hormones
Financial Support: This work is supported by the National Institute of Health [1R01HD111706-01]