An overview of the toxic effect of potential human carcinogen Microcystin-LR on testis

Abstract

The worldwide occurrence of cyanobacterial blooms due to water eutrophication evokes extreme concerns. These blooms produce cyanotoxins which are hazardous to living organisms. So far among these toxins, Microcystin-LR (MC-LR) is the most toxic and the most frequently encountered toxin produced by the cyanobacteria in the contaminated aquatic environment. Microcystin-LR is a potential carcinogen for animals and humans, and the International Agency for Research on Cancer has classified Microcystin-LR as a possible human carcinogen. After liver, testis has been considered as one of the most important target organs of Microcystin-LR toxicity. Microcystin-LR crosses the blood-testis barrier and interferes with DNA damage repair pathway and also increases expression of the proto-oncogenes, genes involved in the response to DNA damage, cell cycle arrest, and apoptosis in testis. Toxicity of MC-LR disrupts the motility and morphology of sperm and also affects the hormone levels of male reproductive system. MC-LR treated mice exhibit oxidative stress in testis through the alteration of antioxidant enzyme activity and also affect the histopathology of male reproductive system. In the present review, an attempt has been made to comprehensively address the impact of MC-LR toxicity on testis.

Keywords: DNA damage; Microcystin-LR (MC-LR); Microcystins; Oxidative stress; Spermatogenesis; Testis.

Graphical abstract

Fig. 1

Microcystis aeruginosa bloom in Sagar lake water (A), sample of water containing Microcystis aeruginosa from a contaminated water reservoir (B), structure of microcystin-LR (C).

Fig. 2

HPLC chromatograms of (A) microcystin-LR standard; (B) microcystin extract containing microcystin-LR from microcystis bloom in Sagar lake water and were determined at PDA 238 nm. The injection volume was 20 μl and the retention time of Microcystin-LR was around 2.9.

Fig. 3

In testes, Microcystin-LR (MC-LR) crosses the blood–testis barrier and induces mitochondrial dependent apoptotic pathway in response to DNA damage and/or oxidative stress in spermatogenic cells, Sertoli cells and Leydig cells, resulting in disruption of cytoskeleton and testicular atrophy. At the hormonal level this results in decrease of testosterone level and overall decline in male reproductive potential. MC-LR also acts as a possible human carcinogen due to its potential carcinogenic activity via inhibition of protein phosphatases, which leads to the hyper-phosphorylation of cellular proteins.