TSitologiya i Genetika 2024, vol. 58, no. 5, 92-93
Cytology and Genetics 2024, vol. 58, no. 5, 476–485, doi: https://www.doi.org/10.3103/S0095452724050128

Arecoline hydrobromide promotes the apoptosis of male germ cells

Sun J., Xu S., Ye M., Wang C., Liu L., Ding B., Li X., Wang X., Zhang F., Liang M.

  1. First Affiliated Hospital, Bengbu Medical College, 233030 Bengbu, China
  2. School of Life Science, Bengbu Medical College, 233030 Bengbu, China

Arecoline hydrobromide has been demonstrated to regulate cellular survival and male reproduction. However, the specific roles and regulated genes of arecoline hydrobromide in spermatogenesis are poorly understood. This study aimed to investigate the effects of arecoline hydrobromide on spermatogenesis and associated transcriptome changes. The spermatogenic cell line GC­1 cells were treated with arecoline hydrobromide to determine the effects of proliferation and apoptosis for arecoline hydrobromide in vitro. The ICR mice were treated with arecoline hydrobromide by intragastric administration. The testes and epididymis were used for sperm count, HE staining, apoptosis detection and transcriptome analysis. Cellular morphology was significantly altered and the number of apoptotic cells increased with increasing concentration and duration of arecoline hydrobromide treatment, and cell proliferation was inhibited. Animal experiments showed that the spermatozoa in the experimental groups were significantly reduced compared with that in the control group. Transcriptome sequencing was executed for testes of four­week arecoline hydrobromide treated mice, which identified 181 significant up­regulated genes and 159 significant down­regulated genes which were then analyzed with gene ontology (GO) and revealed some testicular development and hormone­related pathways. The results verified that arecoline hydrobromide inhibited the proliferation and promoted the apoptosis of GC­1 cells, and caused a decrease in the number of spermatozoa and an increase in level of testosterone in mice.

Keywords: Arecoline hydrobromide; GC­1 cells; Apoptosis; Spermatogenesis

TSitologiya i Genetika
2024, vol. 58, no. 5, 92-93

Current Issue
Cytology and Genetics
2024, vol. 58, no. 5, 476–485,
doi: 10.3103/S0095452724050128

Full text and supplemented materials

References

Abbas, G., Kashif, M., Mudassar, et al., Cytotoxic, embryotoxic, insecticidal and anti–microbial activities of standardized Areca catechu nut, Pak. J. Pharm. Sci., 2018, vol. 31, no. 2, pp. 385–392.

Asadi, A., Ghahremani, R., Abdolmaleki, A., et al., Role of sperm apoptosis and oxidative stress in male infertility: A narrative review, Int. J. Reprod. Biomed., 2021, vol. 19, no. 6, pp. 493–504. https://doi.org/10.18502/ijrm.v19i6.9371

Chang, B.E., Liao, M.H., Kuo, M.Y., et al., Developmental toxicity of arecoline, the major alkaloid in betel nuts, in zebrafish embryos, Birth Defects Res., Part A, 2004, vol. 70, no. 1, pp. 28–36. https://doi.org/10.1002/bdra.10136

Chen, X., He, Y., and Deng, Y., Chemical composition, pharmacological, and toxicological effects of betel nut, Evidence Based Complementary Altern. Med., 2021, vol. 2021, p. 1808081. https://doi.org/10.1155/2021/1808081

Di Guardo, F., Vloeberghs, V., Bardhi, E., et al., Low testosterone and semen parameters in male partners of infertile couples undergoing IVF with a total sperm count greater than 5 million, J. Clin. Med., 2020, vol. 9, no. 12, p. 3824. https://doi.org/10.3390/jcm9123824

Ezzatabadipour, M., Azizollahi, S., Sarvazad, A., et al., Effects of concurrent chronic administration of alcohol and nicotine on rat sperm parameters, Andrologia, 2012, vol. 44, no. 5, pp. 330–336. https://doi.org/10.1111/j.1439-0272.2012.01284.x

Fainberg, J. and Kashanian, J.A., Recent advances in understanding and managing male infertility, F1000Research, 2019, vol. 8, pp. 1–8. https://doi.org/10.12688/f1000research.17076.1

Hu, K., He, C., Ren, H., et al., LncRNA Gm2044 promotes 17β–estradiol synthesis in mpGCs by acting as miR–138–5p sponge, Mol. Reprod. Dev., 2019, vol. 86, no. 8, pp. 1023–1032. https://doi.org/10.1002/mrd.23179

Jenardhanan, P., Panneerselvam, M., and Mathur, P.P., Effect of environmental contaminants on spermatogenesis, Semin. Cell Dev. Biol., 2016, vol. 59, pp. 126–140. https://doi.org/10.1016/j.semcdb.2016.03.024

Keskin, M.Z., Budak, S., Zeyrek, T., et al., The relationship between serum hormone levels (follicle–stimulating hormone, luteinizing hormone, total testosterone) and semen parameters, Arch. Ital. Urol. Androl., 2015, vol. 87, no. 3, pp. 194–197. https://doi.org/10.4081/aiua.2015.3.194

Kumar, S., Tobacco and areca nut chewing–reproductive impairments: an overview, Reprod. Toxicol., 2013, vol. 36, pp. 12–17. https://doi.org/10.1016/j.reprotox.2012.11.007

Li, W.Q., Wang. F., Liu Z.M., et al., Gold nanoparticles elevate plasma testosterone levels in male mice without affecting fertility, Small, 2013, vol. 9, nos. 9–10, pp. 1708–1714. https://doi.org/10.1002/smll.201201079

Liu, Y.J., Peng, W., Hu, M.B., et al., The pharmacology, toxicology and potential applications of arecoline: a review, Pharm. Biol., 2016, vol. 54, no. 11, pp. 2753–2760. https://doi.org/10.3109/13880209.2016.1160251

Miyaso, H., Ogawa, Y., and Itoh, M., Microenvironment for spermatogenesis and sperm maturation, Histochem. Cell. Biol., 2022, vol. 157, no. 3, pp. 273–285. https://doi.org/10.1007/s00418-021-02071-z

Neto, F.T., Bach, P.V., Najari, B.B., et al., Spermatogenesis in humans and its affecting factors, Semin. Cell. Dev. Biol., 2016, vol. 59, pp. 10–26. https://doi.org/10.1016/j.semcdb.2016.04.009

Oliveira, P.F., Sousa, M., Silva, B.M., et al., Obesity, energy balance and spermatogenesis, Reproduction, 2017, vol. 153, no. 6, pp. 173–185. https://doi.org/10.1530/REP-17-0018

Peng, W., Liu, Y.J., Wu, N., et al., Areca catechu L. (Arecaceae): a review of its traditional uses, botany, phytochemistry, pharmacology and toxicology, J. Ethnopharmacol., 2015, vol. 164, pp. 340–356. https://doi.org/10.1016/j.jep.2015.02.010

Ramaswamy, S. and Weinbauer, G.F., Endocrine control of spermatogenesis: Role of FSH and LH/testosterone, Spermatogenesis, 2015, vol. 4, no. 2, p. e996025. https://doi.org/10.1080/21565562.2014.996025

Saha, I., Chatterjee, A., Mondal, A., et al., Arecoline augments cellular proliferation in the prostate gland of male Wistar rats, Toxicol. Appl. Pharmacol., 2011, vol. 255, no. 2, pp. 160–168. https://doi.org/10.1016/j.taap.2011.06.010

Shih, Y.T., Chen, P.S., Wu, C.H., et al., Arecoline, a major alkaloid of the areca nut, causes neurotoxicity through enhancement of oxidative stress and suppression of the antioxidant protective system, Free Radical Biol. Med., 2010, vol. 49, no. 10, pp. 1471–1479. https://doi.org/10.1016/j.freeradbiomed.2010.07.017

Volgin, A.D., Bashirzade, A., Amstislavskaya, T.G., et al., DARK classics in chemical neuroscience: arecoline, ACS Chem. Neurosci., 2019, vol. 10, no. 5, pp. 2176–2185. https://doi.org/10.1021/acschemneuro.8b00711

Wang, K., Gao, Y., Wang, C., et al., Is parthanatos involved in varicocele?, DNA Cell Biol., 2022, vol. 41, no. 10, pp. 861–870. https://doi.org/10.1089/dna.2022.0289