Contemporary Comprehensive Review on Arsenic-Induced Male Reproductive Toxicity and Mechanisms of Phytonutrient Intervention

Abstract

Arsenic (As) is a poisonous metalloid that is toxic to both humans and animals. Drinking water contamination has been linked to the development of cancer (skin, lung, urinary bladder, and liver), as well as other disorders such as diabetes and cardiovascular, gastrointestinal, neurological, and developmental damage. According to epidemiological studies, As contributes to male infertility, sexual dysfunction, poor sperm quality, and developmental consequences such as low birth weight, spontaneous abortion, and small for gestational age (SGA). Arsenic exposure negatively affected male reproductive systems by lowering testicular and accessory organ weights, and sperm counts, increasing sperm abnormalities and causing apoptotic cell death in Leydig and Sertoli cells, which resulted in decreased testosterone synthesis. Furthermore, during male reproductive toxicity, several molecular signalling pathways, such as apoptosis, inflammation, and autophagy are involved. Phytonutrient intervention in arsenic-induced male reproductive toxicity in various species has received a lot of attention over the years. The current review provides an in-depth summary of the available literature on arsenic-induced male toxicity, as well as therapeutic approaches and future directions.

The impact of Annona muricata and metformin on semen quality and hormonal profile in Arsenic trioxide-induced testicular dysfunction in male Wistar rat

“…The study showed that arsenic trioxide depleted sperm morphology following its ingestion, which is linked to lipid peroxidation and ROS generation suppressing the hypothalamic Gonadal axis function (88)(89)(90) acting through the AKT signalling pathway. The study is in line with (56,(58)(59)(60)(91)(92)(93)(94), indicating a significant increase in abnormal sperm cells and significant decline in normal sperm cells. However, treatments with MET and ELAM in the ameliorative and protective phase improve sperm morphology.…”

“…Exposure to arsenic forms results in biological dysfunction processes that have resulted in cardiovascular diseases, diabetes, neurocognitive outcomes, and reproductive dysfunction (2,3) linked to oxidative stress. Arsenic-associated male infertility is caused by oxidative stress, which results to altered hormonal profiles, increased oxidative stress, DNA damage, and metabolic issues connected to spermatogenesis and steroidogeneses (4), which acts through the activation of the ERK/AKT/NF-kβ pathway been the primary molecular mechanisms in male infertility following arsenic trioxide exposure (5,6). Its exposure to humans is through drinking water, highly industrialized activities, cosmetics, smoking, and other air sources (7).…”

The Polymorphisms in GSTO Genes (GSTO1 rs4925, GSTO2 rs156697, and GSTO2 rs2297235) Affect the Risk for Testicular Germ Cell Tumor Development: A Pilot Study

“…Some of the most recognized comprise glutathione-dependent reduction reactions of pentavalent methylated arsenic species, monomethylarsenate V and dimethylarsenate V [ 17 , 44 , 45 ]. Arsenic is known for its high toxicity and carcinogenicity, raising the risk for bladder, lung, kidney, and liver cancer development [ 46 ]. Unfortunately, the environmental and occupational exposure to aforementioned arsenic compounds in the association with glutathione S-transferase O1 and O2 polymorphisms could not be assessed in this pilot study.…”

Heavy Metal Levels in Males With Idiopathic Hypogonadotropic Hypogonadism

“…Cd [ 5 ] and As [ 6 ] can disrupt the repair function of DNA damage, leading to genetic mutations and various cancers. Exposure to As may alter the hypothalamic-pituitary-gonadal (HPG) axis, decreasing testosterone synthesis and spermatogenesis [ 7 ]. As a nutritional antioxidant, zinc is crucial in maintaining various cellular pathways.…”