Effects of valproic acid on the reproductive functions of adult male Wistar rats and consequences for offspring

Introduction: Valproic acid can affect the nervous system as well as other systems such as the endocrine and reproductive systems. Exposure to valproic acid is not without harmful side effects. These undesirable effects can lead to infertility. Objective: To assess the effects of valproic acid on reproductive functions in adult male Wistar rats and consequences for offspring. Materials and methods: Twenty-four adult male Wistar rats, weighing between 100 and 300 g, were used. Treatment was administered orally for sixty days. For the study, three batches, each containing eight adult male Wistar rats, were formed and treated as follows: (1) a control batch given distilled water at 10 ml/kg; (2) and (3) batches treated with valproic acid at doses of 200 and 400 mg/kg respectively. The variables studied included physiological measurements, pedigree observations, sexual behavior, fertility, prolificacy and mortinality rates, spermogram and hormone levels. Results: Exposure of adult male Wistar rats to valproic acid at doses of 200 mg/kg and 400 mg/kg led to an alteration in body weight, a significant decrease in the weight of the prostate (p<0.05), testes (p<0.05) and epididymis (p<0.05). Decreases in fertility rate (25%), prolificacy rate (66.67 and 68.75%), and fecundity rate (250 and 275%), as well as an increase in mortinality rate (50 and 45.45%), were observed respectively in batches 2 and 3 treated with valproic acid. This exposure also led to an alteration in sperm parameters. This was illustrated by asthenospermia (p<0.0001), necrospermia (p<0.05), polyspermia (p<0.05) for the 200 mg/kg dose and oligospermia (p<0.05) for the 400 mg/kg dose. Batches treated with valproic acid showed a significant decrease in testosterone levels (p<0.0001) as well as abnormalities such as hemorrhagic syndrome in neonates born to untreated females and alopecia in the pedigree. Conclusion:Prolonged exposure to valproic acid in adult male Wistar rats at doses of 200 mg/kg and 400 mg/kg led to a reduction in prostate, testicular and epididymal weights. This exposure resulted in a decrease in fertility, prolificacy and fecundity and an increase in mortinality. Alterations in sperm parameters and depletion of testosterone levels were noted, as well as abnormalities in ascendants and descendants.