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N-acetyl-l-cysteine modulates multiple signaling pathways to rescue male germ cells from apoptosis induced by chronic hCG administration to rats

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Abstract

The present study was aimed to investigate the beneficial effects of N-acetyl-l-cysteine (NAC, 150 mg/kg bw twice/week) against testicular germ cell apoptosis in rats induced by chronic hCG administration (100 IU/rat/day for 30 days). NAC co-treatment improved serum testosterone, prevented rise in lipid peroxidation, intracellular H2O2 and the activities of antioxidant enzymes in germ cells. Replenishment of intracellular GSH and total antioxidant capacity was seen. There was a marked reduction in TUNEL positive germ cells and expression of caspase-3 (p < 0.01) and PARP cleavage. Pro-apoptotic markers Fas, FasL, caspase-8 were also significantly downregulated. While Bcl-2 was fully restored, rise in Bax, caspase-9, phospho-JNK/JNK and phospho-c-Jun/c-Jun expression was significantly arrested. Anti-apoptotic phospho-Akt/Akt and NF-κB were otherwise found upregulated. Taken together, the above findings demonstrate that NAC intervention rescued the testicular germ cells from demise following chronic hCG treatment through regulation of multiple signaling mechanisms of metazoan apoptosis.

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Acknowledgments

Senior Research Fellowship (SRF) to Ankur Maheshwari from Council of Scientific and Industrial Research (CSIR), New Delhi, India is greatly acknowledged. The study was funded jointly by CSIR and NIHFW.

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No potential conflicts of interest to disclose.

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Authors and Affiliations

  1. Department of Reproductive Biomedicine, National Institute of Health and Family Welfare, Baba Gang Nath Marg, Munirka, New Delhi, 110067, India

    Ankur Maheshwari, M. M. Misro & Archana Aggarwal

  2. Department of Zoology, Kurukshetra University, Kurukshetra, 136119, India

    Ankur Maheshwari & Rajnesh K. Sharma

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  1. Ankur Maheshwari
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  2. M. M. Misro
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  3. Archana Aggarwal
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Correspondence to M. M. Misro.

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Maheshwari, A., Misro, M.M., Aggarwal, A. et al. N-acetyl-l-cysteine modulates multiple signaling pathways to rescue male germ cells from apoptosis induced by chronic hCG administration to rats. Apoptosis 17, 551–565 (2012). https://doi.org/10.1007/s10495-012-0703-8

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