Development of a murine model to study the effect of metabolic syndrome on endometrial function and female fertility

CARNOVALE N; VELAZQUEZ C; ABRAMOVICH D; MASSILLO C; MADANES D; STELLA I; SCALISE G; MC CORMACK B; OLIVARES C; BILOTAS M; MERESMAN G

Congreso; LXV reunión anual de la sociedad argentina de investigación clínica (SAIC); 2020

The correct functioning of the reproductive axis depends on an adequate energy balance, therefore studying the influence of the physiological alterations associated with metabolic syndrome (MS) as a single entity is important to understand the associated female fertility problems. The aim of this study was to develop and characterize an optimal experimental in vivo model for MS with the future objective of studying the effect of MS on endometrial physiology and reproductive disorders. Twenty one-days-old female C57BL/6 mice were divided in two groups: one received a high fat diet (HF) and the other one, a control diet (CD) for 13 or 14 weeks. Animals were weighed weekly and a significant increase in weight of HF mice was observed at week 11 (p˂0,05). On the last day of experiment, glycemia was measured using a glucometer with One Touch test strips at two fasting times: 4 h and 6 h, observing a significant increase in HF group after the longer fast (p˂ 0,01). Animals were sacrificed at estrus and the blood was collected by cardiac puncture for biochemical analyses of cholesterol, triglycerides, HDL and LDL. The uterine horns, the adipose tissue and the liver were removed and fixed. Significant changes in cholesterol, LDL and HDL were observed in HF mice (p˂0,05), but no changes were found in triglycerides levels. Adipose tissues were weighed, seeing a significant increase in the weight of visceral and gonadal adipose tissue in HF mice (p˂0,05). Steatosis was evaluated by H-E staining in liver sections, observing a fatty liver in the HF group. As an approximation to study the reproductive profile, PCNA cell proliferation, was measured assessed by PCNA immunohistochemistry and endometrial glands and leukocytes were count in H-E stained uterine sections in a preliminary experiment, but no changes were observed between groups. These results are promising for the further efforts to evaluate the effect of MS on female reproduction.