A brief exposure to cadmium impairs Leydig cell regeneration in the adult rat testis

Xiaolong Wu,Huang Wang,Xiaoling Guo,Xiaomin Chen,Ren-Shan Ge,Jianpeng Liu,Songyi Zhou,Hong-Shan Ge,Lili Li,Guimin Wang

doi:10.1038/s41598-017-06870-0

Abstract

Cadmium is an endocrine disruptor, impairing male reproduction. The objective of this study is to investigate whether cadmium affects rat Leydig cell regeneration and to dissect the underlying mechanism. Adult male Sprague-Dawley rats received a single intraperitoneal injection (i.p.) of 0, 0.5 or 1.0 mg/kg of cadmium chloride, followed by ethane dimethane sulfonate (EDS) treatment to eliminate adult Leydig cells 20 days later. Compared to control (0 dose), cadmium treatment reduced serum testosterone levels by days 21, 35, and 56 after EDS treatment. Serum luteinizing hormone (LH) levels were also affected by day 56, the only time point examined. There were fewer regenerated Leydig cells in the cadmium-treated testis on days 35 and 56 after EDS treatment. Further studies demonstrated that the mRNA or protein levels of Leydig (Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b3, and Hsd11b1), non-Leydig (Fshr and Dhh), and gonadotroph (Lhb) cells were also significantly lower in cadmium-treated animals. Since LH and desert hedgehog (DHH) are critical factors for Leydig cell differentiation, our result demonstrated that the lower doses of cadmium exposure, even briefly, may permanently damage Leydig cell regeneration.

Highlights

In recent years, the increased incidence of human male infertility has been of a great concern
These indicate that the cadmium reduces the number of Leydig cells possibly before 35 days after ethane dimethane sulfonate (EDS), a stage for stem Leydig cells into immature Leydig cells
Adult population of Leydig cells in the testis are completely eliminated by a single intraperitoneal injection of 75 mg/kg EDS23

Summary

Introduction

The increased incidence of human male infertility has been of a great concern. Exposure to cadmium induced germ cell loss and decreased sperm production[4], which may account for the increased incidence of male infertility It seems that the testicular somatic cells such as Sertoli and Leydig cells are the targets of cadmium. The development or regeneration of Leydig cells are regulated by many factors, including gonadotroph-secreted LH and non-Leydig testicular cell factors (such as desert hedgehog, DHH, and anti-Müllerian hormone, AMH)[11, 12] Both the expressions and secretions of DHH and AMH are regulated by the gonadotroph-secreted follicle-stimulating hormone (FSH, encoded by Fshb), which binds to its receptor (FSHR, encoded by Fshr) on Sertoli cells[13, 14]. We investigated whether a brief exposure to lower doses of cadmium might affect Leydig cell regeneration in the adult rat testis and whether such effect, if arise, was caused by changes in the precursor cells or micro-environment that regulates the developmental cells

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