Sex and timing of gonadectomy relative to puberty interact to influence weight, body composition, and feeding behaviors in mice

Gonadal sex steroids are important regulators of energy balance in adult rodents, and gonadectomy (GDX) has opposing effects on weight gain in sexually mature males and females. Puberty is associated with the emergence of sex differences in weight, body composition, and feeding behaviors, yet the role of gonadal hormones at puberty remains unclear. To address this, we performed GDX or sham surgery in male and female C57Bl/6 mice at postnatal day (P)25 (prepubertal) or P60 (postpubertal) timepoints and measured weight and body compo-sition for 35 days, after which ad libitum and operant food intake was measured using Feeding Experimentation Device 3 (FED3s) in the home cage. Consistent with previous studies, postpubertal GDX caused weight gain in females and weight loss in males and increased adiposity in both sexes. However, prepubertal GDX decreased weight gain and altered body composition across the adolescent transition (P25 to P60) in males but had no effect in females. Despite the varied effects on weight, GDX decreased food intake and motivation for food as assessed in operant tasks regardless of sex or timing of surgery relative to puberty. Our findings indicate that GDX interacts with both sex and age at surgery to influence weight, body composition, and feeding behavior.

Automated summary

Gonadal sex steroids play a crucial role in regulating energy balance in adult rodents and their effects on weight gain differ in sexually mature males and females after gonadectomy (GDX). However, the role of gonadal hormones during puberty remains uncertain. In this study, we performed GDX or sham surgery on male and female C57Bl/6 mice at prepubertal (P25) or postpubertal (P60) stages and measured weight, body composition, and feeding behaviors. Our results showed that postpubertal GDX led to weight gain in females and weight loss in males, while prepubertal GDX affected weight gain and body composition changes only in males. However, GDX decreased food intake and motivation for food in all groups regardless of sex or timing of surgery relative to puberty.