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Early physical and motor development of mouse offspring exposed to valproic acid throughout intrauterine development
Jelena Podgorac1, Vesna Pešić2, Željko Pavković2
1Department of Neurophysiology, Institute for Biological Research "Siniša Stanković", University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia.
Insights
Prenatal exposure to valproic acid (VPA) delays physical development and motor maturation in mice offspring, with effects intensifying at higher doses. Continuous monitoring of VPA-exposed offspring is crucial for early detection of developmental issues.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Prenatal exposure to antiepileptic drugs (AEDs), specifically valproic acid (VPA), is linked to developmental delays and physical malformations in children.
- The precise early signs, postnatal evolution, and dose-dependent effects of VPA on neurodevelopment remain incompletely understood.
Purpose of the Study:
- To investigate the impact of maternal VPA exposure across a range of doses on the early physical and neuromotor development of mouse offspring.
- To assess dose-specific effects of VPA on somatic growth and motor system maturation during the early postnatal period.
Main Methods:
- Mice dams were administered varying doses of VPA (50, 100, 200, 400mg/kg/day) during breeding and gestation.
- Offspring were evaluated for body weight gain, eye opening, surface righting reflex (SRR), and tail suspension test (TST) at postnatal days 5, 10, and 15.
Main Results:
- All VPA doses reduced offspring body weight and delayed eye opening.
- VPA-exposed offspring exhibited delayed righting reflexes (SRR) and increased time to completion.
- Tail suspension test (TST) showed dose-dependent alterations in immobilization latency and atypical motor activity (swinging, curling) at higher VPA doses.
Conclusions:
- Maternal VPA exposure during gestation results in delayed somatic development and postponed neuromotor maturation in offspring, irrespective of dose.
- Higher VPA doses exacerbate these developmental deficits.
- Early and continuous monitoring of general health and motor milestones in prenatally VPA-exposed offspring is recommended for identifying developmental irregularities.
Abstract:
Clinical research has identified developmental delay and physical malformations in children prenatally exposed to the antiepileptic drug (AED) valproic acid (VPA). However, the early signs of neurodevelopmental deficits, their evolution during postnatal development and growth, and the dose effects of VPA are not well understood. The present study aimed to examine the influence of maternal exposure to a wide dose range (50, 100, 200 and 400mg/kg/day) of VPA during breeding and gestation on early physical and neuromotor development in mice offspring. Body weight gain, eye opening, the surface righting reflex (SRR) and tail suspension test (TST) were examined in the offspring at postnatal days 5, 10 and 15. We observed that: (1) all tested doses of VPA reduced the body weight of the offspring and the timing of eye opening; (2) offspring exposed to VPA displayed immature forms of righting and required more time to complete the SRR; (3) latency for the first immobilization in the TST is shorter in offspring exposed to higher doses of VPA; however, mice in all groups exposed to VPA exhibited atypical changes in this parameter during the examined period of maturation; (4) irregularities in swinging and curling activities were observed in animals exposed to higher doses of VPA. This study points to delayed somatic development and postponed maturation of the motor system in all of the offspring prenatally exposed to VPA, with stronger effects observed at higher doses. The results implicate that the strategy of continuous monitoring of general health and achievements in motor milestones during the early postnatal development in prenatally VPA-exposed offspring, irrespectively of the dose applied, could help to recognize early developmental irregularities.
