Gestational or lactational exposure to L-mimosine in rats: maternal toxicity, fetal growth retardation, and compromised skeletal development

Abstract

L-mimosine, a compound found in legumes of the Leucaena genus, is known for its ability to disrupt the cell cycle and its toxic properties. Its effects during critical periods such as gestation and lactation remain poorly understood. This study aimed to evaluate the potential toxic effects of L-mimosine in rats exposed during these periods, as well as its transfer through biological fluids, such as milk, to offspring. Oral doses of 140, 240, or 340 mg/kg of maternal body weight were administered, and a control group (CO), which received only the vehicle, was included. During gestation, dams received L-mimosine from gestational days 6–21, whereas exposure through lactation occurs from postnatal days (PNDs) 1–21. Maternal and offspring body weight gain (BWG), maternal food consumption, and clinical signs were monitored, and offspring physical and reflex development was also assessed. Milk and maternal blood samples were collected for L-mimosine quantification, and the phytotoxin was detected in both biological fluids. Following in utero exposure, marked toxic effects were observed, especially at the 240 mg/kg dose. In dams, significant reductions (P < 0.05) in total BWG and food intake, alopecia, decreased relative right kidney weight, increased relative thymus weight, and splenic lymphoid hyperplasia were recorded. The offspring presented significant reductions (P < 0.05) in litter weight at birth and at PND 42, an increased number of stillbirths, delayed incisor eruption, and physical malformations. Histopathological analyses revealed mild to moderate alterations in the kidneys and spleen. In contrast, lactational exposure resulted in no noteworthy maternal or offspring effects, despite confirmed L-mimosine excretion in milk. These findings underscore the pronounced vulnerability of the developing organism to L-mimosine when exposure occurs in utero, emphasizing the importance of gestational periods as critical windows for toxicological risk.