Maternal metformin treatment in obese pregnant dams normalizes neonatal sensory-motor reflexes
Abstract
Background: Maternal overweight and obesity have reached epidemic proportions over recent decades, with detrimental effects on offspring metabolism and neurodevelopment. Metformin, commonly used to treat type 2 diabetes mellitus and gestational diabetes, is being investigated for use in maternal obesity due to its weight-loss-promoting, glucose-lowering, and insulin-sensitizing effects. Metformin may improve maternal metabolic state and support early sensory-motor development in offspring.
Methods: Three-week-old female C57BL/6NCrl mice were fed either a standard diet (SD, 9 kJ% fat, low sucrose content; CO group) or a Western-style diet (WSD, 45 kJ% fat, high sucrose content; OB group) from weaning through mating, gestation, and lactation. A subgroup of pregnant WSD-fed mice received metformin hydrochloride (target dose 380 mg/kg/d; OB + M group), dissolved in drinking water during gestation. At mid-gestation, a small cohort of pregnant dams was assessed for their metabolic profile. After delivery, pups were culled to six per litter at postnatal day (P) 2, and reflex ontogeny - such as righting, negative geotactic, and cliff-avoidance responses - was evaluated until P9 as a measure of early neurodevelopment.
Results: Feeding a WSD resulted in approximately 20% heavier dams in the OB group by the time of mating. Metformin administration led to gestational weight gain of about 56%, compared to OB weight gain of approximately 64%. Plasma leptin levels, perigonadal white…
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Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
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