Abstract

This study investigated the relationship between germ and Leydig cell death, testosterone, and adiponectin levels in cadmium-mediated acute toxicity. Cadmium chloride was administered in a single dose to five groups of rats: G1 (0.9% NaCl) and G2 to G5 (0.67, 0.74, 0.86, and 1.1 mg Cd/kg). After 7 days, the animals were euthanized, and the testosterone and testes were analyzed. Dose-dependent Cd accumulation in the testes was identified. At 0.86 and 1.1 mg/kg, animals exhibited marked inflammatory infiltrate and disorganization of the seminiferous epithelium. While Leydig cells were morphologically resistant to Cd toxicity, massive germ cell death and DNA oxidation and fragmentation were observed. Although numerical density of Leydig cells was unchanged, testosterone levels were significantly impaired in animals exposed to 0.86 and 1.1 mg Cd/kg, occurring in parallel with the reduction in total adiponectins and the increase in high-molecular weight adiponectin levels. Our findings indicated that Leydig and germ cells exhibit differential microstructural resistance to Cd toxicity. While germ cells are a primary target of Cd-induced toxicity, Leydig cells remain resistant to death even when exposed to high doses of Cd. Despite morphological resistance, steroidogenesis was drastically impaired by Cd exposure, an event potentially related to the imbalance in adiponectin production.

Highlights

  • As life-threatening inorganic pollutants are widely distributed in soil, water, and food, heavy metal poisoning is a serious public health problem worldwide [1]

  • Adiponectins present with potent immunomodulation and antiapoptotic and antioxidant properties [54, 55], our findings suggest that testicular adiponectins can have a role other than attenuation of inflammatory damage and germ cell death

  • Our findings indicate that Cd-mediated toxicity is associated with morphological and functional testis damage

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Summary

Introduction

As life-threatening inorganic pollutants are widely distributed in soil, water, and food, heavy metal poisoning is a serious public health problem worldwide [1]. Cadmium-mediated toxicity has been associated with inhibition of expression of important regulatory molecules, such as focal adhesion kinase, Src kinases, and tyrosine phosphatase SHP2; these are essential for maintaining the morphofunctional integrity of the germinative epithelium, especially the Sertoli cell barrier and Sertoli-germ cell interactions [7,8,9,10] These changes are related to molecular imbalance of the testis microenvironment and have a Oxidative Medicine and Cellular Longevity negative impact on steroidogenesis and spermatogenesis; this results in severe consequences such as hypogonadal syndromes and disturbance of male fertility [11, 12]. Investigation of the relationship between adiponectins, testis structure, and function can introduce a new perspective on the regulatory mechanisms activated in the testes in response to Cd toxicity

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