Chronic chromium exposure-induced changes in testicular histoarchitecture are associated with oxidative stress: Study in a non-human primate (Macaca radiata Geoffroy)

Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, India.
Human Reproduction (Impact Factor: 4.57). 11/2005; 20(10):2801-13. DOI: 10.1093/humrep/dei148
Source: PubMed


Reproductive toxicity of chromium is in dispute despite positive findings in rodents. Recently we reported epididymal toxicity of hexavalent chromium (CrVI) in bonnet monkeys and in this paper we report its testicular toxicity.
Adult monkeys (Macaca radiata) were given drinking water containing CrVI (100, 200, 400 p.p.m.) for 6 months and testes were removed for ultrastructural and biochemical analyses.
CrVI treatment disrupted spermatogenesis, leading to accumulation of prematurely released spermatocytes, spermatids and uni- and multinucleate giant cells in the lumen of seminiferous tubules. Transmission electron microscopy revealed granulation of chromatin and vacuolation between acrosomal cap and manchette microtubules of elongated spermatids and in the Golgi area of round spermatids. Pachytene spermatocytes had fragmented chromatin and swollen mitochondria with collapsed cristae. Spermatocytes and spermatogonia in the basal compartment were unaffected. Macrophages containing phagocytosed sperm and dense inclusions in Sertoli cells were seen. Specific activities of the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase and concentrations of the non-enzymatic antioxidants glutathione, vitamins A, C and E decreased, while concentrations of H(2)O(2) and hydroxyl radicals increased in the testis of chromium-treated monkeys. Withdrawal of chromium treatment for 6 months normalized spermatogenesis and the status of pro- and antioxidants in the testis.
CrVI disrupts spermatogenesis by inducing free radical toxicity, and supplementation of antioxidant vitamins may be beneficial to the affected subjects.

Download full-text


Available from: Subramanian Senthivinayagam
  • Source
    • "Several studies reported OS as a common cause of infertility and altered spermatogenesis in men (Tremellen, 2008; Turner and Lysiak, 2008; Aruldhas et al., 2005). The objectives of our study were to examine OS-related biochemical aspects, essential metals and androgenic status, as well as morphological changes of the testes of male Wistar rats subacutely intraperitoneally (i.p.) exposed to Cd. Focusing on testicular toxicity of Cd, we assessed OS by measuring superoxide anion radical (O 2 À ), activities of total SOD and GST; CAT; lipid peroxidation (LPO); reduced glutathione (GSH) and oxidized glutathione (GSSG); the status of certain biometals [zinc (Zn), copper (Cu), iron (Fe) and magnesium (Mg)]; and testosterone level in the testes. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The objective of our study was to examine testicular toxicity of cadmium (Cd), focusing on oxidative stress (OS), essential metals and androgenic status and morphological changes. Male Wistar rats [controls and four Cd-subgroups (n = 6) organized according to the exposure (1, 3, 10 and 21 days)] were intraperitoneally (i.p.) treated with 1 mg CdCl2/kg/day. Testicular Cd deposition was noticed from the 1st day. After 10 and 21 days, copper (Cu) and iron (Fe) increased by 60-109% and 43-67%, respectively, while zinc (Zn) decreased by 24-33%. During 1-21 days of the exposure, decrease in testicular total superoxide dismutase (SOD) and total glutathione-s-transferase (GST) activities occurred gradually by 30-78% and 15-84%, respectively, while superoxide anion radical (O2-) increased gradually by 114-271%. After 10-21 days, decrease in testicular catalase (CAT) activity appeared by 13-31%. After 21 days, malondialdehyde (MDA) decreased by 44% and the ratio of oxidized glutathione/reduced glutathione (GSSG/GSH) increased by 130% in testes of the rats exposed to Cd. Additionally, decreased testicular testosterone level and the relative testes mass, along with induced microscopic and macroscopic changes were occured, what can be explained as the consequence of instantly developed OS, impaired essential metals status and Cd testicular deposition.
    Full-text · Article · Sep 2015 · Food and Chemical Toxicology
  • Source
    • "The decrease in testicular activities of these enzymatic antioxidants in exercised rats may be due to increased ROS production (Seema et al., 2007). In the present study, the decreased GSH level induced by exhaustive exercise seriously impaired the catalytic activities of GSH-dependent enzymes like GPx and GST (Aruldhas et al., 2005; Flora et al., 2008). The testicular GSH/GSSG ratio, an index of oxidative stress (Chainy et al., 1997), also decreased in the exercised animals. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Prolonged and strenuous exercise has been proposed as a possible source of male-factor infertility. Forced intensive swimming has also been identified as one source of a dysfunctional male reproduction system. The present study evaluated the possible protective role of α-lipoic acid and N-acetylcysteine (NAC) on intensive swimming-induced germ-cell depletion in adult male rats. Forced exhaustive swimming of 1 hr/day, 6 days/week for 8 consecutive weeks resulted in a significant (P < 0.05) reduction in epididymal sperm; testicular androgenic enzyme activities; and plasma and intra-testicular testosterone; and produced different types of germ cells in the seminiferous epithelium cycle. Conversely, plasma corticosterone levels and sperm-head abnormalities increased. Western-blot analysis showed a considerable decrease in testicular StAR protein expression whereas reverse-transcriptase PCR analysis showed no significant change in cytochrome P450scc (Cyp11a1) gene expression. Significant (P < 0.05) elevation in testicular reactive oxygen species (ROS), lipid peroxidation, protein carbonyl content versus reduction in glucose-6-phosphate dehydrogenase, glutathione peroxidase, glutathione S-transferase, and caspase-3 activities along with a depletion in the glutathione pool, mitochondrial membrane potential (▵ψm), and intracellular ATP generation. A considerable level of DNA damage in testicular spermatogenic cells were also noted following forced extensive swimming. Alpha-lipoic acid and NAC supplementation prevented the swimming-induced testicular spermatogenic and steroidogenic disorders by lowering ROS generation. We therefore conclude that intensive forced swimming causes germ-cell depletion through the generation of ROS and depletion of steroidogenesis in the testis, which can be protected by the co-administration of α-lipoic acid and NAC. Mol. Reprod. Dev. 2014. © 2014 Wiley Periodicals, Inc.
    Full-text · Article · Sep 2014 · Molecular Reproduction and Development
  • Source
    • "Reproductive toxicity of hexavalent chromium [Cr (VI)] in mammals including human beings has recently been reported. Chromium (VI)-induced testicular as well as ovarian toxicity has been demonstrated in laboratory mammals (Murthy et al., 1996; Elbetieha and Al-Hamood, 1997; Aruldhas et al., 2005; Acharya et al., 2006; Subramanian et al., 2006). A few reports correlated chronic occupational chromium exposures to abnormal semen quality in men (Li et al., 2001; Danadevi et al., 2003; Kumar et al., 2005). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Exposure to sublethal hexavalent chromium (as 2 and 4 mg L⁻¹ potassium dichromate for 1 and 2 months) during late preparatory to mid prespawning phase of annual reproductive cycle severely affected the pituitary-ovarian axis of a teleost Channa punctatus. Gonadosomatic index (GSI), ovarian histopathology, immunocytochemistry of the pituitary gonadotrophs (LHβ-immunoreactive cells), and serum 17β-estradiol level revealed distinct dose and duration-dependent effects. Gonadosomatic index was declined. Diameter of ovary as well as ovarian follicles was reduced along with a distinct variation in the percentage of follicles. The greater percentage of previtellogenic follicles (stage I) and decline in vitellogenic ones (stage II and stage III) compared to control indicated the arrest of follicular development. The percentage of atretic follicles was also increased indicating toxic impact of metal on ovary. Decreased serum level of ovarian steroid 17β-estradiol further indicated the same. Chromium interference of the pituitary was demonstrated as atrophy and less immunointensity of LH-immunoreactive gonadotrophs. Thus, the hexavalent chromium impaired the pituitary-ovarian axis affecting at the sites of both pituitary and ovary.
    Full-text · Article · Jul 2012 · Environmental Toxicology
Show more