Dietary phytoestrogen, diosgenin interrupts metabolism, physiology and reproduction of the Swiss albino mice: possible mode of action as an emerging environmental contaminant, endocrine disruptor and reproductive toxicant

Dietary phytoestrogens are the main sources of environmental contamination because of their estrogen-mimic and endocrine-disrupting effects and pose a threat to microbial, soil, plant and animal health. Diosgenin, a phytosteroid saponin, is being used as nutraceuticals, dietary supplements, contraceptive, and in the hormone replacement therapy against numerous diseases and disorders. Due to the lack of research on the safety and probable adverse side effects of diosgenin, this work aimed to evaluate the endocrine disrupting and reproductive toxicity of diosgenin in the albino mice with respect to acute toxicity (OECD-423), repeated dose 90 days oral toxicity (OECD-468), and F 1 extended one generation reproductive toxicity (OECD-443) studies. Diosgenin is a slightly toxic compound and LD 50 for male and female mice is 546.26 and 538.72 mg/kg, respectively. Chronic exposure of diosgenin (10, 50, 100, and 200 mg/kg) generated oxidative stress, depleted antioxidant enzymes, disturbed homeostasis of the reproductive hormones, and interrupted steroidogenesis, germ cell apoptosis, gametogenesis, sperm quality, estrous cycle and reproductive performance in the F 0 and F 1 offspring. Long-term oral exposure of diosgenin to the mice interrupted the endocrine and reproductive functions, and triggered the transgenerational reproductive toxic effects in F 0 and F 1 offspring, validating the possible mode of action as an emerging environmental contaminant, endocrine disruptor and reproductive toxicant in Swiss albino mice.