The present study aimed to investigate the oral toxic effects of 1/10 LD50 and 1/5 LD50 of thiamethoxam (TMX), a neonicotinoid insecticide, on the reproductive system of female Wistar rats. Thirty female rats were divided into three groups and supplied orally with either; saline solution, 1/10 LD50 of TMX (156 mg/kg) or 1/5 LD50 of TMX (312 mg/kg). The daily administration was extended for 30 days. Investigating the parameters of oxidative stress, hormonal levels, histopathological alterations, and the apoptotic markers (P53, BAX, BCL-2, and caspase-3) was performed in the uterus and ovary of rats. Results showed significant changes in the body weight gain, and relative weight of the left and right ovaries and uterus. Moreover, luteinizing hormone (LH), estradiol (ED), and progesterone (PG) serum levels were not significantly altered following TMX oral administration. The level of follicle-stimulating hormone in the TMX-exposed group (156 mg/kg) was significantly increased; however, a significant decrease was observed in TMX-exposed animals (312 mg/kg). TMX induced significant oxidative stress in exposed groups by reducing the activities of superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT), and elevating malondialdehyde (MDA) levels. Following hematoxylin and eosin staining, the microscopic examination revealed deteriorated luteal cells with vacuolation in the corpus luteum, a follicle containing a degenerated oocyte and degeneration/necrosis of the circular muscle layer with a high rate of apoptotic cells in TMX-exposed animals. TMX induced transcriptional alterations in apoptosis-related genes shifting towards the activation of the intrinsic apoptotic pathway. Collectively, results suggest the toxic effect of the TMX on the reproductive health of female Wistar rats.

Neonicotinoid insecticides usage is currently widespread, but this poses a challenge when considering the potential for occupational and environmental contamination. One of the most extensively used insecticides is thiamethoxam (TMX), a second-generation neonicotinoid insecticide. This study aimed to see if sub-lethal dosages of TMX insecticide had any negative impacts on epididymal sperm parameters, serum hormones, oxidative status, and testicular histology. The experimental cohorts were given a low dose of TMX (156 mg/kg bw), a high dose of TMX (312 mg/kg bw), or an untreated control for eight weeks. The sperm count, percent of viability, motility, and motility progressing and fructose level significantly decreased in both TMX-treated groups compared to the control group. Furthermore, TMX administration induced sperm morphological defects, serum hormone disturbances as significant reduction testosterone level, oxidant/antioxidant status imbalance as significant decline in catalase (CAT) and glutagthione peroxidase (GSH) content and significant rise in malondialdehyde (MDA) level and testicular histopathological alternation. TMX caused significant increase DNA damage in testicular tissue represented in tail DNA percent, comet percent, comet length, tail moment, and Olive moment. In conclusion, TMX exposure may have a deleterious impact on male albino rats' fertility through spermatogenesis, steroidogenesis and testicular redox status disruption, and testicles DNA impairment.

P53 is the second most frequently mutated tumor suppressor gene representing about 40-60% of all cases of breast cancer (BC) patients. Even though BC can be considered a highly curable disease when detected early. It is often diagnosed at a later stage, due to fragile economic circumstances and lack of awareness. Thereby, the aim of the present study is to establish high resolution melting (HRM) assay as a rapid and economic screening tool for identifying presence of mutations in P53 gene among familial and non-familial BC patient hoping to assist in diagnosis and disease management. Blood samples were collected from preoperatively Egyptian BC women, and genomic DNA was extracted from 25 familial, 25 non-familial BC patients and 25 healthy volunteers. Real-time PCR amplicons for exons 5-8 in P53 gene have been performed, followed by HRM to detect mutations. Herein, we have detected 85 mutations in exons 5, 7, and 8. Our results have revealed that presence of positive variants in P53 exons as detected by HRM, were shown to be more frequent among BC patients than the control group (P =0.001). Moreover, percentage of BC patients who responded to hormonal therapy (HT) were found to be more among familial than non-familial group (P= 0.001). Furthermore, we have found that hormonal receptors estrogen (ER) and progestogen (PR) were more expressed among both familial and non-familial BC patients compared to expression of human epidermal receptor 2 (Her2) among the same groups. Interestingly and according to our results, patients with single mutation were found to be at lower tumor stage when compared to those with multiple exon mutations who had higher tumor stage (P=0.018). HRM was established as an economic prognostic tool for identifying mutations in the P53 gene, which might be correlated to the risk of Egyptian BC development in women. Yet, a larger sample size needs to be studied, since all research findings underline the importance of establishing an Egyptian BC database taking into consideration clinical and pathological criteria, that can play a crucial role in drug responsiveness and disease management.

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