Chronic administration of sodium valproic acid slows pubertal maturation in inbred DBA/2J mice: skeletal, histological, and endocrinological evidence.
Sodium valproic acid (VPA) has been reported to occasionally delay pubertal maturation in children. In the current study, we sought to establish a valid animal model with which to further investigate the neuroendocrinological sequelae of VPA administration. Male and female DBA/2J mice were weaned at 2 weeks of age and administered either VPA (17-20 mg/kg/day) or control solution via drinking water. Animals were weighed and sacrificed via decapitation at 4, 6, or 8 weeks of age. Testes and ovaries were prepared for histological analyses. In addition, the length of the left humerus bone from each animal was obtained as an index of skeletal growth, and trunk blood was assayed for circulating follicle-stimulating hormone (FSH) and prolactin (PRL). For males, testicular weights of the animals receiving VPA were significantly lower than those of control animals at all three sampling ages. No between-group differences were found for body weight at any sampling age, and yet the rate of skeletal maturation (as indexed by humerus length) was decreased significantly for the VPA-treated males at all three sampling periods. Additionally, while hormone levels did not consistently differ, histological analyses of the gonadal tissue demonstrated significantly decreased rats of spermatogenesis at all sampling points for VPA-treated animals. For females, chronic VPA administration led to a significant reduction in uterine weight at the 4 and 6 week sampling periods, and yet by 8 weeks of age the uterine weights for the two groups did not differ.(ABSTRACT TRUNCATED AT 250 WORDS)
Snyder
P J
PJ
Department of Psychiatry, Medical College of Pennsylvania, Pittsburgh, USA.
Badura
L L
LL
D000818:Animals; D005260:Female; D006066:Gonads / Q000187:drug effects / Q000473:pathology; D006128:Growth / Q000187:drug effects; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009929:Organ Size / Q000187:drug effects; D012741:Sexual Maturation / Q000187:drug effects*; D013997:Time Factors; D014635:Valproic Acid / Q000494:pharmacology*
D014635:Valproic Acid