Toxic effects of sodium fluoride on cell proliferation and apoptosis of Leydig cells from young mice

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ORIGINAL PAPER

Toxic effects of sodium fluoride on cell proliferation and apoptosis of Leydig cells from young mice Guo hua Song & Rui Li Wang & Zhao Yang Chen & Bin Zhang & Hai Long Wang & Mao Lin Liu & Ji Ping Gao & Xiao Yan Yan

Received: 25 October 2013 / Accepted: 1 July 2014 / Published online: 30 July 2014 # University of Navarra 2014

Abstract The biological effects of fluoride on human health are often extensive, either beneficial or detrimental. Among the various effects of fluoride exposure in different organs, the reproductive tract is particularly susceptible to disruption by fluoride at a sufficient concentration. It has attracted much attention to the effect of sodium fluoride on male fertility, gestational female, and offspring. Herein, we applied a widespread natural compound sodium fluoride (NaF) and investigated the effects of acute NaF exposure on Leydig cells, including their proliferation, apoptosis, and signal pathway changes. Our results demonstrated that high dosage of NaF could inhibit cell proliferation by stress-induced apoptosis, which was confirmed by cellular and molecular evidences. We found that fluoride exposure affected the expression levels of stress response factors, signal transduction components, and apoptosis-related proteins, including caspase3/caspase-9, B-cell lymphoma 2 (Bcl-2), and Bax. This study suggests that the complex effects of fluoride on Leydig cells are closely related to its dosage. Keywords Sodium fluoride . Leydig cell . Apoptosis . Caspase-3 . Caspase-9 G. Song (*) : R. L. Wang : Z. Y. Chen : B. Zhang : H. L. Wang : M. L. Liu : J. P. Gao Laboratory Animal Center, Shanxi Medical University, Road Xinjian 56, Taiyuan 030001, China e-mail: [email protected] X. Y. Yan Department of Biology, Taiyuan Normal University, Taiyuan 030031, China

Introduction Fluoride, an essential mineral element for mammals and humans, has a disruptive effect on various tissues in the body. The latest report showed that around 200 million people from 25 countries around the world are affected by fluoride toxicity [19], and China is one of the most populous countries in the world and threatened by the dreadful fate of fluorosis [3]. It is well known that the effects of fluoride on biological tissues are often extensive. In recent years, damage by fluoride to hard tissues and brain tissue in animals has been studied [9]. Although fluoride can cause the different effects on different organ systems of the body, the reproductive tract is susceptible to be disrupted by a high concentration of fluoride [9]. In the reproductive system, sperm counts and sperm volume in healthy men are reported to have declined, which are correlated with the increase of environmental pollutants [15]. It has been reported that fluoride-induced testicular oxidative stress resulted in the damage of sperm cell membrane, which might be accountable for the inhibition of testicular spermatogenesis and reduced sperm activity [16]. Some studies in animals indicated that the occurrence of adverse reproductive and develo