High fructose diet is associated with the global metabolic syndrome (MtS) pandemic. MtS develops in early life, depending on prenatal and postnatal nutritional status. We hypothesized that ovariectomy increases the chances of developing MtS in adult offspring following high fructose intake by the mother. Pregnant C57BL/6J mouse dams drank water with or without 20% fructose during pregnancy and lactation. After weaning, the pups were fed regular chow. The offspring were evaluated until they were 7 months of age after the mice in each group, both sexes, were gonadectomized at 4 weeks of age. The offspring (both sexes) of the dams who had high fructose intake developed MtS. In the offspring of dams who drank tap water, orchiectomy increased the body weight gain and body fat accumulation, while ovariectomy increased the body fat accumulation as compared to the sham controls. In the offspring of dams with high fructose intake, orchiectomy decreased the body weight gain, body fat accumulation, visceral adiposity, and glucose intolerance, while ovariectomy exacerbated all of them as compared to the sham operations. These data indicate that ovariectomy encourages the development of MtS in adult offspring after maternal high fructose intake, while orchiectomy prevents the development of MtS. The sex difference indicates that male and female sex hormones play contradictory roles in the development of MtS.

Keywords: Fructose, Metabolic syndrome, Orchiectomy, Ovariectomy, Sex difference