Differential effects of p,p′-DDE on testis and liver mitochondria:Implications for reproductive toxicology

Abstract

a b s t r a c tThe release of environmental contaminants can contribute to impaired male fertility. The bioenergetics of isolated liver mitochondria have been used as a toxicological indicator, an inexpensive first line model to screen possible effects of several substances. Here we report the effects of 2,2-bis(4-chlorophenyl)-1,1-dichloro-ethylene (DDE) on the bioenergetical parameters of testicular mitochondria. A significant decrease in repolarization potential (after a phosphorylative cycle), state 3 respiration and uncoupled respiration, with a concomitant increase in lag phase was found, demonstrating a decrease in mitochondrial function. Importantly, there was also a clear increase in maximum potential in DDE-treated testis mitochondria, which was not mirrored by more commonly used liver mitochondria. Indeed, comparative studies showed that testis and liver mitochondria have strikingly different sensitivities and patterns of response to DDE, indicating that testis mitochondria should be used as a primary toxicological model for a proper evaluation of putative effects of environmental toxicants on the bioenergetics of spermatogenesis and male fertility.

Organochloride pesticides impaired mitochondrial function in hepatocytes and aggravated disorders of fatty acid metabolism

“…Our findings that OCPs decreased mitochondria number and ATP levels were consistent with previous observations in rats27. In addition, we provided new evidences for mitochondria dysfunction, including decreased membrane potential, defects in OCR and decreased ATP production in OCP exposure group.…”

Mitochondrial dysfunction induced by Bisphenol A is a factor of its hepatotoxicity in rats

“…EDCs have been reported to cause mitochondrial injury (Anjum et al, ; Mota et al, ; Kaur et al, ). Perturbation of mitochondrial respiratory chain and induction of oxidative stress are considered to be the major factors leading to mitochondrial injury (Indo et al, ; Anjum et al, ).…”

Mitochondria and mammalian reproduction

“…As a whole testis mitochondria have been shown to possess specific bioenergetical and controlled proton leak characteristics that distinguish them from mitochondria from other organs, consuming less oxygen in order to generate approximately the same maximum electric potential (Amaral et al, 2008aMota et al, 2009;Rodrigues et al, 2010). This suggests that, unlike what is usually the case, testicular mitochondria should be considered as the primary mitochondrial models to test the effect of distinct substances on male gametogenesis, and not be substituted by other in vitro models, such as commonly used liver mitochondria (Mota et al, 2011;Tavares et al, 2009).…”

“…It should noted that mitochondrial function is most often studied in terms of dysfunction induced by pathological conditions or toxic substances (pharmacological agents, environmental contaminants, distinct pathologies, etc. ), and how these dysfunctions may ultimately affect the reproductive system (Aly and Khafagy, 2011;Amaral et al, 2008aBanu et al, 2011;Miyamoto et al, 2010;Mota et al, 2011;Svechnikov et al, 2009;Wang et al, 2009Wang et al, , 2010. Using different aspects of mitochondrial function as damage indicators in several disease models and, conversely, as diagnostic tools in Assisted Reproductive Technologies (ART), has increased in recent years, in terms of functional sperm analysis (Aitken et al, 2012;Dorn and Scorrano, 2010;Gallon et al, 2006;Marchetti et al, 2002;Marchetti et al, 2012;Nakada et al, 2006;Ruiz-Pesini et al, 1998;Sanchez-Partida et al, 2008;Sousa et al, 2011), and oocyte quality assessment (Van Blerkom, 2011;Wang and Sun, 2007).…”