ORIGINAL ABSTRACT

Kalach (KL) is a glyphosate (G)-based herbicide extensively used in agricultural and urban areas in Tunisia. It has been reported that G crosses the placenta in pregnant rats, potentially disrupting organ function in offspring. The present study examined the effects of prenatal and lactational exposure to KL on thyroid function, bone integrity, and phosphocalcic homeostasis in rat offspring. Pregnant rats were divided into two groups, group A (control group) and group B, exposed to KL (each mother rat received 0.07 mL of KL diluted in 1 mL of water by gavage). On postnatal day 14, plasma samples were analyzed for thyroid hormones, calcium, and phosphorus. Histology and immunohistochemical study of bone and thyroid, Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy assessed alterations. Additionally, we complemented the in vivo study with an in silico study. We found that KL induced hypothyroidism, necrosis in thyroid tissue, and phosphocalcic imbalance, leading to skeletal abnormalities. Structural and mineralization defects in bone were confirmed by FTIR and XRD analysis. The in silico study revealed that G bids to growth hormone receptors and thyroglobulin with good affinity, corroborating the in vivo findings. In conclusion, KL may interfere with bone tissue, growth hormone receptors, and thyroglobulin, impair hypothyroidism, and function as an endocrine disruptor exposure. Consequently, KL induces disorganization of the femoral growth plate.