1α,25‐dihydroxyvitamin D₃ supplementation alleviates perfluorooctanesulfonate acid‐induced reproductive injury in male mice: Modulation of Nrf2 mediated oxidative stress response

Abstract

Perfluorooctanesulfonate acid (PFOS) is a typical persistent organic pollutant that widely exists in the environment. To clarify the toxic effects and mechanisms of PFOS and to find effective intervention strategies have been attracted global attention. Here, we investigated the effects of PFOS on the male reproductive system and explored the potential protective role of 1α,25-dihydroxyvitamin D 3 (1α,25(OH) 2 D 3 ).Our results showed that 1α,25(OH) 2 D 3 intervention significantly improved PFOSinduced sperm quality decline and testicular damage. Moreover, 1α,25(OH) 2 D 3 aggrandized the total antioxidant capacity. Furthermore, after PFOS exposure, the transcription factor nuclear factor erythroid-related factor 2 (Nrf2) was adaptively increased together with its target genes, such as HO-1, NQO1, and SOD2. Meanwhile, 1α,25(OH) 2 D 3 ameliorated PFOS-induced augment of Nrf2 and target genes.These findings indicated that 1α,25(OH) 2 D 3 might attenuate PFOS-induced reproductive injury in male mice via Nrf2-mediated oxidative stress. K E Y W O R D S 1α,25(OH) 2 D 3 , Nrf2, oxidative stress, perfluorooctanesulfonate acid, reproductive toxicity 1 | INTRODUCTION Perfluorooctanesulfonic acid (PFOS) is a representative synthetic organo-fluorine compound, which has been widely used as a stain repellent and anti-stick material due to its excellent hydrophobic and lipophobic properties. 1 However, PFOS is difficult to degrade and widely exists in water, dust, soil, and other environmental media. 2,3 Noteworthy, PFOS generates a bioaccumulation effect. Drinking water, contaminated food consumption, product usage, and occupational exposure are the main approaches to PFOS exposure. PFOS has been extensively detected in human blood, umbilical cord blood, breast milk, and other samples worldwide. 4 Therefore, PFOS exposure has become a global environmental problem, and it is of great importance to clarify the toxic effects and mechanisms of PFOS and to find effective intervention strategies.In human body, PFOS combines with proteins, such as liver fatty acid transporters in the liver and albumin in the plasma. Liver is the primary target of PFOS, which can cause typical hepatic toxicity by disrupting glucose and lipid metabolism. [5][6][7][8] Recent studies have discovered that PFOS can also induce immune toxicity, 9 cardiotoxicity, 10 and neurotoxicity. 11 Furthermore, PFOS has significant reproductive

Perfluorooctane sulfonate‐induced apoptosis in kidney cells by triggering the NOX4/ROS/JNK axis and antagonism of cannabidiol

“…5 In addition, PFOS induces astrocyte apoptosis and alters the dopamine system in mammals, leading to neurotoxicity. 6,7 For the human and animal reproductive systems, PFOS can cause reproductive toxicity by reducing the quality of germ cells, 8 and disrupting the normal structure of reproductive organs and embryonic development. 9,10 Experiments in animals and in vitro have as well shown the oxidative effects and toxicity of PFOS on tissues and cells, resulting in multiple organs (e.g., kidney, liver, heart, and lung) with severe damage.…”