Obesity, ovarian GLUT4 expression, and reproductive dysfunction: Insights from Zucker fatty rat

Abstract

The impact of obesity on female reproductive health is considerable; despite the well-established association between nutritional status, obesity, and reproductive health, the mechanisms through which obesity impacts the reproductive axis remain poorly understood. For this reason, this study aims to investigate the expression of protein glucose transporter 4 (GLUT4) in the ovary and their association with morphophysiological alterations in the ovaries and uterus in a genetic obesity model, the Zucker fatty (fa/fa) rat. Various parameters were evaluated, including zoometric and metabolic measurements, estrous cyclicity, ovulation, and follicular development. The ovaries and uterus were histologically analyzed using hematoxylin-eosin staining. Furthermore, ovarian GLUT4 protein levels were estimated by Western blotting and fluorescence microscopy to investigate its association with metabolic and reproductive dysfunctions observed in this model. Zucker fatty rats exhibited significant body weight and adiposity index increases, accompanied by elevated cholesterol, triglycerides, and insulin levels. Conversely, progesterone levels were found to be significantly reduced. Histological analysis of ovarian morphology revealed pre-cystic follicles, a diminished follicular population, and a reduced number of corpora lutea. Additionally, a decrease in ovarian GLUT4 protein expression was observed. The uterine analysis demonstrated a smaller overall area, with notable reductions in both endometrial and myometrial thickness and fewer uterine glands. These findings indicate that in Zucker fatty rats, decreased ovarian GLUT4 protein expression and impaired glucose homeostasis are strongly associated with significant morphological alterations in the ovaries and uterus.