Early-life exposure to dimethoate-induced reproductive toxicity: evaluation of effects on pituitary-testicular axis of mice.

In utero and lactational exposure to organophosphate dimethoate exerted toxic impact on the reproductive system of male mice. Pregnant mice were exposed to 4, 8, and 16 mg/kg of the pesticide, the sublethal doses (2.5, 5, and 10% of Lethal Dose(50) [LD(50)]), via gavaging from gestation day (GD) 6 to postnatal day (PND) 21. The effects on the male reproductive system were evaluated at two stages: at prepubertal age (PND 22) and at the postpubertal age of PND 63. Gonadal inhibition was reflected in the significant reduction of weight and distinct histopathological alteration of testis and epididymis as well as in decreased sperm counts, which could be linked to hormonal imbalance caused by dimethoate interference of reproductive axis. Disruption of pituitary-testicular axis was shown in the weak immunointensity of luteinizing hormone (LH) cells, reduction in their size and number, and lowered plasma LH and testosterone levels as observed in the neonates exposed to two higher tested doses. In addition, the direct toxic impact of the pesticide on the testicular Leydig cells and inhibition of steroidogenesis could be suggested. Drastic reduction in the testosterone level (approximately 70%) was suggestive of this effect. The adverse effects were persisted in the young adult mice. Developmental toxicity was evident in the highest dose-exposed (10% LD(50)) group where GD length and stillbirths were significantly increased along with a decrease of body weight and anogenital distance of the fetus. Maternal exposure of pesticide during gestation and lactation periods thus adversely affected the pituitary-testicular axis of mice neonates, which further caused reproductive dysfunctioning of young adult mice.