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Transient inhibitory effect of methoxychlor on testicular steroidogenesis in rat: an in vivo study
S Vaithinathan1, B Saradha, P P Mathur
1Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Pondicherry 605014, India.
Abstract:
Methoxychlor, an organochlorine pesticide, has been reported to induce reproductive abnormalities in male reproductive tract. To get more insight into the mechanism(s) of gonadal toxicity provoked by methoxychlor, we investigated whether treatment with methoxychlor at low observed adverse effect level (LOAEL) would alter the activities of steroidogenic enzymes such as Delta(5)3beta-hydroxysteroid dehydrogenase (3beta-HSD) and Delta(5)17beta-hydroxysteroid dehydrogenase (17beta-HSD), the expression levels of steroidogenic acute regulatory (StAR) protein and androgen binding protein (ABP) in the testis of adult male rats. The experimental rats were exposed to a single dose of methoxychlor (50 mg/kg body weight) orally. The rats were killed at 0, 3, 6, 12, 24 and 72 h following treatment using anesthetic ether and testes were collected, processed and used to measure the activities of 3beta-HSD, 17beta-HSD, levels of hydrogen peroxide produced and the expression levels of StAR protein, and ABP. Methoxychlor administration resulted in a sequential reduction in the expression of StAR protein and activities of 3beta-HSD, 17beta-HSD with concomitant increase in the levels of hydrogen peroxide in the testis. These changes were significant between 6-12 h following treatment. The levels of ABP declined at 6-12 h following exposure to methoxychlor. The present study demonstrates transient effect of methoxychlor at LOAEL on testicular steroidogenesis and the possible role of hydrogen peroxide in mediating these effects.
Insights
Methoxychlor exposure transiently reduces key steroidogenic enzymes and StAR protein in rat testes, increasing hydrogen peroxide. This pesticide
Area of Science:
- Toxicology
- Endocrinology
- Reproductive Biology
Background:
- Methoxychlor, an organochlorine pesticide, is linked to male reproductive abnormalities.
- Understanding methoxychlor's gonadal toxicity mechanisms is crucial for assessing reproductive health risks.
Purpose of the Study:
- To investigate methoxychlor's effects on testicular steroidogenic enzymes and protein expression at a low observed adverse effect level (LOAEL).
- To explore the role of hydrogen peroxide in mediating methoxychlor-induced testicular toxicity.
Main Methods:
- Adult male rats were orally administered a single dose of methoxychlor (50 mg/kg).
- Testes were collected at various time points (0-72 h) post-treatment.
- Assays measured Delta(5)3beta-hydroxysteroid dehydrogenase (3beta-HSD), Delta(5)17beta-hydroxysteroid dehydrogenase (17beta-HSD) activities, StAR protein, androgen binding protein (ABP) levels, and hydrogen peroxide production.
Main Results:
- Methoxychlor significantly reduced StAR protein expression and 3beta-HSD and 17beta-HSD activities between 6-12 hours.
- A concomitant increase in testicular hydrogen peroxide levels was observed.
- Androgen binding protein (ABP) levels declined within 6-12 hours post-exposure.
Conclusions:
- Methoxychlor exerts a transient inhibitory effect on testicular steroidogenesis at the LOAEL.
- Hydrogen peroxide may play a role in mediating the observed testicular toxicity.
- These findings highlight the potential endocrine-disrupting effects of methoxychlor on male reproductive health.
