Curtis S. Davis¹, Kara C. Phillips¹, David S. Hydock^1,

Despite its clinical use, the reversibility of gonadotropin-releasing hormone agonist (GnRHa) treatment after discontinuation remains poorly understood, particularly regarding offspring physical activity. Therefore, this study examined voluntary wheel-running activity as an assessment of physical activity in male and female offspring born to female rats that received GnRHa treatment early in life followed by its discontinuation. Four-week-old female Sprague-Dawley rats received either daily 100 µg subcutaneous injections of the gonadotropin releasing hormone agonist (GnRHa) triptorelin as a puberty blocker (P, n=6) or saline as a control (C, n=6) daily for 28 days. Injections then discontinued and female rats were paired with male rats for breeding. Male (M) and female (F) Offspring (O) from the P and C females were housed in cages outfitted with voluntary running wheels for 56 days (M WR (M+WR+PO, n=3; F+WR+PO, n=3; M+WR+CO, n=3; F+WR+CO, n=3). Wheel running activity was then assessed for 8 weeks. A significant main parent treatment effect (p=0.0213) and sex effect (p=0.0228) was observed for total WR distance (M+WR+PO, 158 ± 54 km; M+WR+CO, 378 ± 27 km; F+WR+PO 373 ± 58 km; F+WR+CO 738 ± 187 km), but there was no parent treatment x sex interaction (p=0.4988). No significant main effects or interactions were observed in weekly WR distances during Week 1, but significant parent treatment effects were observed in Weeks 2-5 (p=0.0157, p=0.0131, p=0.0114, p=0.0263, respectively) with significant main sex effects observed in Weeks 2, 3, and 4 (p=0.0026, p=0.0088 and p= 0.0169 respectively). No significant main effects or interactions were observed in WR distances for Weeks 6-8 (p>0.05). Male and female offspring from GnRHa treated and discontinued female rats had lower WR activity than their respective control counterparts suggesting that physical activity levels may be impacted by the temporary disruption in maternal reproductive development even after discontinuation of pubertal suppression.

discontinuation, gonadotropin-releasing hormone agonist, maternal, offspring, physical activity