Investigation into the effects of sodium valproate on prepubertal mouse gonads in vivo
Objective Sodium valproate (SV) is a widely used anti-epileptic drug with well-established reproductive and teratogenic effects, yet its impact on the developing prepubertal reproductive system remains poorly understood. This study investigated the effects of prepubertal SV exposure on gonadal development, including folliculogenesis, testicular architecture and steroidogenic gene expression in…
A recent study examined the effects of sodium valproate (SV) on the developing reproductive systems of prepubertal mice. The research aimed to understand how brief exposure to the anti-epileptic drug could influence the formation of ovarian follicles and testicular structures in both male and female mice.
CD1 mouse pups received intraperitoneal injections of either saline (used as a control) or low or high doses of SV (50 or 100 mg/kg) on specific postnatal days (PND) 6, 8, and 10. After 17 PND, the animals were euthanized, and their gonads were removed for examination.
The ovaries and testes were analyzed histologically using hematoxylin and eosin staining. Quantitative assessments of ovarian follicle number, stage, and health, as well as testicular tubule morphology and key cell counts (germ, Sertoli, spermatogonial stem cells, and interstitial/Leydig cells), were performed using immunofluorescence and automated image analysis.
Additionally, the expression of critical steroidogenic genes (CYP11A1, STAR, CYP19A1 in ovaries; INSL3, STAR, CYP11A1 in testes) was measured using reverse transcription quantitative PCR (RT-qPCR).
The results showed that SV exposure did not significantly affect ovarian follicle number, distribution, or health. Similarly, testicular morphology and the density of Sertoli, spermatogonial stem cells, and interstitial cells remained unaffected by SV exposure. However, a trend toward reduced germ cell density was observed in male mice at the high dose of SV, although this difference did not reach statistical significance (P = 0.058).
Crucially, SV exposure did not alter steroidogenic gene expression in either ovaries or testes across all treatment groups.
This study is the first to assess the short-term effects of prepubertal SV exposure on gonadal development in both sexes. While the findings suggest that brief SV exposure during the prepubertal window does not cause overt gonadotoxicity, the observed trend of reduced testicular germ cell density in males warrants further investigation using longer exposure durations and functional fertility endpoints.
This research aims to provide more comprehensive data to inform clinical risk assessments for pediatric patients receiving SV.
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