Effects of Bisphenol A and Diethylstilbestrol on Estrogen Receptor Expression and Male Fertility
DOI:
https://doi.org/10.18192/riss-ijhs.v2i1.1523Keywords:
Bisphenol A, diethylstilbestrol, Endocrine Disrupting Chemicals (EDCs), xenoestrogens, male infertility, spermatogenesis, Estrogen Receptor Alpha (ERα), Estrogen Receptor Beta (ERβ), G-protein Coupled Receptor (GPR30)Abstract
Infertility is defined as a couple’s inability to conceive after one year of unprotected intercourse. Male reproductive pathologies are the predominate cause of at least 20% of cases of infertility; making male infertility is an important issue in overall population health. Endocrine disrupting chemicals (EDCs) can impair spermatogenesis by creating hormonal imbalances and morphological changes. DES and BPA are both exogenous estrogens, also known as xenoestrogens. Estrogen has an important role in fertility of males as well as females: it has a role in the overall endocrine balance required to allow spermatogenesis. Effects on the hypothalamic-pituitary-gonadal axis may be monitored by assessing for upregulation of estrogen receptors α and -B (ERα and ERβ), as well as the novel estrogen receptor g-protein coupled receptor 30 (GPR30). Controversy surrounds the mechanisms endocrine disruption associated with these chemicals, and whether the negative effects on fertility are relevant at low doses, or only at high doses which are systemically toxic. Analysis of literature associated with this ongoing research will enrich our understanding of the molecular bases for impairment of spermatogenesis and male fertility associated with exposure to EDCs, specifically DES and BPA. Once completed, this study will contribute to knowledge in the fields of population health, environmental health, and molecular genetics. With a more thorough understanding of the impact of EDCs on fertility, it is hoped that governments will further prevent exposure by better regulating the use of compounds such as DES and BPA.
References
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Aikawa, H., Koyama, S., Matsuda, M., Nakahashi, K., Akazome, Y., & Mori, T. (2004). Relief effect of vitamin A on the decreased motility of sperm and the increased incidence of malformed sperm in mice exposed neonatally to bisphenol A. Cell and Tissue Research, 315(1), 119-24. doi: 10.1007/ s00441-003-0806-1
Akingbemi, B. T. (2005). Estrogen regulation of testicular function. Reproductive Biology and Endocrinology, 3, 51-64. doi: 10.1186/1477-7827-3-51
Anahara, R., Yoshida, M., Toyama, Y., Maekawa, M., Kai, M., Ishino, F.... & Mori, C. (2006). Estrogen agonists, beta-estradiol, bisphenol A, and diethylstilbestrol, decrease cortactin expression in the mouse testis. Archives of Histology and Cytology, 69(2), 101-107. doi: 10.1679/ aohc.69.101
Benachour, N., Moslemi, S., Sipahutar, H., & Seralini, G. E. (2007). Cytotoxic effects and aromatase inhibition by xenobiotic endocrine disrupters alone and in combination. Toxicology and Applied Pharmacology, 222(2), 129- 140. doi: 10.1016/j.taap.2007.03.033
Cederroth, C. R., Schaad, O., Descombes, P., Chambon, P., Vassalli, J. D., & Nef, S. (2007). Estrogen receptor alpha is a major contributor to estrogen-mediated fetal testis dysgenesis and cryptorchidism. Endocrinology, 148(11), 5507- 5519. doi: 10.1210/en.2007-0689
Filardo, E., Quinn, J., Pang, Y., Graeber, C., Shaw, S., Dong, J., & Thomas, P. (2007). Activation of the novel estrogen receptor G protein-coupled receptor 30 (GPR30) at the plasma membrane. Endocrinology, 148(7), 3236-3245. doi: 10.1210/en.2006-1605
Foster, W. G., Neal, M. S., Han, M. S., & Dominguez, M. M. (2008). Environmental contaminants and human infertility: Hypothesis or cause for concern? Journal of Toxicology and Environmental Health. Part B Critical Reviews, 11(3-4), 162-176. doi: 10.1080/10937400701873274
Funakoshi, T., Yanai, A., Shinoda, K., Kawano, M. M., & Mizukami, Y. (2006). G protein-coupled receptor 30 is an estrogen receptor in the plasma membrane. Biochemical and Biophysical Research Communications, 346(3), 904- 910. doi: 10.1016/j.bbrc.2006.05.191
Heindel, J. J. (2003). Endocrine Disruptors and Human Health. World Health Organization. Report of the joint IPCS-Japan workshop on “Endocrine disruptors: Research needs and future directions,” 19-22. Retrieved from http://www.who.int/ipcs/publications/endocrine_disruptors/en/ japan_workshop_report.pdf
Hendry, W. J. 3rd, Weaver, B.P., Naccarato, T. R., & Khan, S. A. (2006) Differential progression of neonatal diethyl-stilbestrol-induced disruption of the hamster testis and seminal vesicle. Reproductive Toxicology, 21(3), 225-240. doi: 10.1016/j.reprotox.2005.09.014
Hong, Y., Wang, J., Zhang, P., Yang, S., Song, K., Yu, F., & Liu, W. (2010) Histopathological and gene expression analysis of mice exposed to diethylstilbestrol. Toxicology Mechanisms and Methods, 20(3), 105-111. doi: 10.3109/15376510903572631
Kato, H., Furuhashi, T., Tanaka, M., Katsu, Y., Watanabe, H., Ohta, Y., & Iguchi, T. (2006). Effects of bisphenol A given neonatally on reproductive functions of male rats. Reproductive Toxicology, 22(1), 20-29. doi: 10.1016/ j.reprotox.2005.10.003
Kobayashi, T., Shirai, M., Sakaue, M., Murakami, M., Ochiai, H., Arishima, K., & Yamamoto, M. (2009). Effects of maternal exposure to low doses of DES on testicular steroidogenesis and spermatogenesis in male rat offspring. The Journal of Reproduction and Development, 55(6), 629-637. doi: 10.1262/jrd.20223
Koh, K. B., Toyama, Y., Komiyama, M., Adachi, T., Fukata, H., & Mori, C. (2006). Neonatal administration of diethylstilbestrol has adverse effects on somatic cells rather than germ cells. Reproductive Toxicology, 22(4), 746-53. doi: 10.1016/j.reprotox.2006.07.006.
Li, D., Zhou, Z., Qing, D., He, Y., Wu, T., Miao, M...& Yuan W. (2009). Occupational exposure to bisphenol-A (BPA) and the risk of self-reported male sexual dysfunction. Human Reproduction, 25(2), 519-527. doi: 10.1093/humrep/dep381
Ma, A., Yang, X., Wang, Z., Shi, D., & Chen, Y. (2008). Adult exposure to diethylstilbestrol induces spermatogenic cell apoptosis in vivo through increased oxidative stress in male hamster. Reproductive Toxicology, 25(3), 367-373. doi: 10.1016/j.reprotox.2007.12.007
Merck Sharp & Dohme Corp (2006a). Bisphenol A product monograph. In the Merck Index Online. Retrieved from https://www.rsc.org/merck-index/
Merck Sharp & Dohme Corp (2006b). Diethylstilbestrol product monograph. In the Merck Index Online. Retrieved from https://www.rsc.org/merck-index/
Mikkilä, T. F., Toppari, J., & Paranko, J. (2006). Effects of neonatal exposure to 4-tert-octylphenol, diethylstilbestrol, and flutamide on steroidogenesis in infantile rat testis. Toxicological Sciences: an official journal of the Society of Toxicology, 91(2), 456-466. doi: 10.1093/toxsci/kfj156
Nakamura, D., Yanagiba, Y., Duan, Z., Ito, Y., Okamura, A., Asaeda, N... & Nakajima, T. (2010). Bisphenol A may cause testosterone reduction by adversely affecting both testis and pituitary systems similar to estradiol. Toxicology Letters, 194(1-2), 16-25. doi: 10.1016/j.toxlet.2010.02.002
O’Donnell, L., Robertson, K. M., Jones, M. E., & Simpson, E. R. (2001). Estrogen and spermatogenesis. Endocrine Reviews, 22(3), 289-318. doi: 10.1210/er.22.3.289
Otto, C., Fuchs, I., Kauselmann, G., Kern, H., Zevnik, B., Andreasen, P.,... Fritzemeier, K.H. (2009). GPR30 does not mediate estrogenic responses in reproductive organs in mice. Biology of Reproduction, 80(1), 34-41. doi: 10.1095/biolreprod.108.071175
Phillips, K. P., & Foster, W. G. (2008a). Endocrine toxicants with emphasis on human health risks. Journal of Toxicology and Environmental Health. Part B Critical Reviews, 11(3-4), 149-151. doi: 10.1080/00927870701873115
Phillips, K. P., & Foster, W. G. (2008b). Key developments in endocrine disrupter research and human health. Journal of Toxicology and Environmental Health. Part B Critical Reviews, 11(3-4), 322-344. doi: 10.1080/10937400701876194
Phillips, K. P., Foster, W. G., Leiss, W., Sahni, V., Karyakina, N., Turner, M. C... & Krewski, D. (2008). Assessing and managing risks arising from exposure to endocrine-active chemicals. Journal of Toxicology and Environmental Health. Part B Critical Reviews, 11(3-4), 351-372. doi: 10.1080/10937400701876657
Phillips, K. P., & Tanphaichitr N. (2008). Human exposure to endocrine disrupters and semen quality. Journal of Toxicology and Environmental Health. Part B, Critical Reviews, 11(3-4), 188-220. doi: 10.1080/10937400701873472
Salian, S., Doshi, T., & Vanage, G. (2009a). Impairment in protein expression profile of testicular steroid receptor coregulators in male rat offspring perinatally exposed to bisphenol A. Life Sciences, 85(1-2), 11-18. doi: 10.1016/ j.lfs.2009.04.005
Salian, S., Doshi, T., & Vanage, G. (2009b). Neonatal exposure of male rats to bisphenol A impairs fertility and expression of sertoli cell junctional proteins in the testis. Toxicology, 265(1- 2), 56-67. doi: 10.1016/j.tox.2009.09.012
Salian, S., Doshi, T., & Vanage, G. (2009c). Perinatal exposure of rats to bisphenol A affects the fertility of male off- spring. Life Sciences, 85(21- 22), 742-752. doi: 10.1016/ j.lfs.2009.10.004
Shin, J. H., Kim, T. S., Kang, I. H., Kang, T. S., Moon, H. J., & Han, S. Y. (2009). Effects of postnatal administration of diethylstilbestrol on puberty and thyroid function in male rats. Journal of Reproduction and Development, 55(5), 461-466. doi: 10.1262/jrd.20169
Tyl, R. W., Myers, C. B., Marr, M. C., Sloan, C. S., Castillo, N. P., Veselica, M. M.... & Waechter, J. M. Jr. (2008). Two-generation reproductive toxicity study of dietary bisphenol A in CD-1 (Swiss) mice. Toxicological Sciences, 104(2), 362 -384. doi: 10.1093/toxsci/kfn084
Tyshenko, M. G., Phillips, K. P., Mehta, M., Poirier, R., & Leiss W. (2008). Risk communication of endocrine-disrupting chemicals: improving knowledge translation and transfer. Journal of Toxicology and Environmental Health. Part B Critical Reviews, 11(3-4), 345-350. doi: 10.1080/10937400701876293
Volle, D. H., Decourteix, M., Garo, E., McNeilly, J., Fenichel, P., Auwerx, J... & Benahmed, M. (2009). The orphan nuclear receptor small heterodimer partner mediates male infertility induced by diethylstilbestrol in mice. The Journal of Clinical Investigation, 119(12), 3752-3764. doi: 10.1172/JCI38521
Warita, K., Sugawara, T., Yue, Z. P., Tsukahara, S., Mutoh, K., Hasegawa, Y... & Hoshi, N. (2006). Progression of the dose-related effects of estrogenic endocrine disruptors, an important factor in declining fertility, differs between the hypothalamo-pituitary axis and reproductive organs of male mice. Journal of Veterinary Medical Science, 68(12), 1257-1267. doi: 10.1292/jvms.68.1257
Aikawa, H., Koyama, S., Matsuda, M., Nakahashi, K., Akazome, Y., & Mori, T. (2004). Relief effect of vitamin A on the decreased motility of sperm and the increased incidence of malformed sperm in mice exposed neonatally to bisphenol A. Cell and Tissue Research, 315(1), 119-24. doi: 10.1007/ s00441-003-0806-1
Akingbemi, B. T. (2005). Estrogen regulation of testicular function. Reproductive Biology and Endocrinology, 3, 51-64. doi: 10.1186/1477-7827-3-51
Anahara, R., Yoshida, M., Toyama, Y., Maekawa, M., Kai, M., Ishino, F.... & Mori, C. (2006). Estrogen agonists, beta-estradiol, bisphenol A, and diethylstilbestrol, decrease cortactin expression in the mouse testis. Archives of Histology and Cytology, 69(2), 101-107. doi: 10.1679/ aohc.69.101
Benachour, N., Moslemi, S., Sipahutar, H., & Seralini, G. E. (2007). Cytotoxic effects and aromatase inhibition by xenobiotic endocrine disrupters alone and in combination. Toxicology and Applied Pharmacology, 222(2), 129- 140. doi: 10.1016/j.taap.2007.03.033
Cederroth, C. R., Schaad, O., Descombes, P., Chambon, P., Vassalli, J. D., & Nef, S. (2007). Estrogen receptor alpha is a major contributor to estrogen-mediated fetal testis dysgenesis and cryptorchidism. Endocrinology, 148(11), 5507- 5519. doi: 10.1210/en.2007-0689
Filardo, E., Quinn, J., Pang, Y., Graeber, C., Shaw, S., Dong, J., & Thomas, P. (2007). Activation of the novel estrogen receptor G protein-coupled receptor 30 (GPR30) at the plasma membrane. Endocrinology, 148(7), 3236-3245. doi: 10.1210/en.2006-1605
Foster, W. G., Neal, M. S., Han, M. S., & Dominguez, M. M. (2008). Environmental contaminants and human infertility: Hypothesis or cause for concern? Journal of Toxicology and Environmental Health. Part B Critical Reviews, 11(3-4), 162-176. doi: 10.1080/10937400701873274
Funakoshi, T., Yanai, A., Shinoda, K., Kawano, M. M., & Mizukami, Y. (2006). G protein-coupled receptor 30 is an estrogen receptor in the plasma membrane. Biochemical and Biophysical Research Communications, 346(3), 904- 910. doi: 10.1016/j.bbrc.2006.05.191
Heindel, J. J. (2003). Endocrine Disruptors and Human Health. World Health Organization. Report of the joint IPCS-Japan workshop on “Endocrine disruptors: Research needs and future directions,” 19-22. Retrieved from http://www.who.int/ipcs/publications/endocrine_disruptors/en/ japan_workshop_report.pdf
Hendry, W. J. 3rd, Weaver, B.P., Naccarato, T. R., & Khan, S. A. (2006) Differential progression of neonatal diethyl-stilbestrol-induced disruption of the hamster testis and seminal vesicle. Reproductive Toxicology, 21(3), 225-240. doi: 10.1016/j.reprotox.2005.09.014
Hong, Y., Wang, J., Zhang, P., Yang, S., Song, K., Yu, F., & Liu, W. (2010) Histopathological and gene expression analysis of mice exposed to diethylstilbestrol. Toxicology Mechanisms and Methods, 20(3), 105-111. doi: 10.3109/15376510903572631
Kato, H., Furuhashi, T., Tanaka, M., Katsu, Y., Watanabe, H., Ohta, Y., & Iguchi, T. (2006). Effects of bisphenol A given neonatally on reproductive functions of male rats. Reproductive Toxicology, 22(1), 20-29. doi: 10.1016/ j.reprotox.2005.10.003
Kobayashi, T., Shirai, M., Sakaue, M., Murakami, M., Ochiai, H., Arishima, K., & Yamamoto, M. (2009). Effects of maternal exposure to low doses of DES on testicular steroidogenesis and spermatogenesis in male rat offspring. The Journal of Reproduction and Development, 55(6), 629-637. doi: 10.1262/jrd.20223
Koh, K. B., Toyama, Y., Komiyama, M., Adachi, T., Fukata, H., & Mori, C. (2006). Neonatal administration of diethylstilbestrol has adverse effects on somatic cells rather than germ cells. Reproductive Toxicology, 22(4), 746-53. doi: 10.1016/j.reprotox.2006.07.006.
Li, D., Zhou, Z., Qing, D., He, Y., Wu, T., Miao, M...& Yuan W. (2009). Occupational exposure to bisphenol-A (BPA) and the risk of self-reported male sexual dysfunction. Human Reproduction, 25(2), 519-527. doi: 10.1093/humrep/dep381
Ma, A., Yang, X., Wang, Z., Shi, D., & Chen, Y. (2008). Adult exposure to diethylstilbestrol induces spermatogenic cell apoptosis in vivo through increased oxidative stress in male hamster. Reproductive Toxicology, 25(3), 367-373. doi: 10.1016/j.reprotox.2007.12.007
Merck Sharp & Dohme Corp (2006a). Bisphenol A product monograph. In the Merck Index Online. Retrieved from https://www.rsc.org/merck-index/
Merck Sharp & Dohme Corp (2006b). Diethylstilbestrol product monograph. In the Merck Index Online. Retrieved from https://www.rsc.org/merck-index/
Mikkilä, T. F., Toppari, J., & Paranko, J. (2006). Effects of neonatal exposure to 4-tert-octylphenol, diethylstilbestrol, and flutamide on steroidogenesis in infantile rat testis. Toxicological Sciences: an official journal of the Society of Toxicology, 91(2), 456-466. doi: 10.1093/toxsci/kfj156
Nakamura, D., Yanagiba, Y., Duan, Z., Ito, Y., Okamura, A., Asaeda, N... & Nakajima, T. (2010). Bisphenol A may cause testosterone reduction by adversely affecting both testis and pituitary systems similar to estradiol. Toxicology Letters, 194(1-2), 16-25. doi: 10.1016/j.toxlet.2010.02.002
O’Donnell, L., Robertson, K. M., Jones, M. E., & Simpson, E. R. (2001). Estrogen and spermatogenesis. Endocrine Reviews, 22(3), 289-318. doi: 10.1210/er.22.3.289
Otto, C., Fuchs, I., Kauselmann, G., Kern, H., Zevnik, B., Andreasen, P.,... Fritzemeier, K.H. (2009). GPR30 does not mediate estrogenic responses in reproductive organs in mice. Biology of Reproduction, 80(1), 34-41. doi: 10.1095/biolreprod.108.071175
Phillips, K. P., & Foster, W. G. (2008a). Endocrine toxicants with emphasis on human health risks. Journal of Toxicology and Environmental Health. Part B Critical Reviews, 11(3-4), 149-151. doi: 10.1080/00927870701873115
Phillips, K. P., & Foster, W. G. (2008b). Key developments in endocrine disrupter research and human health. Journal of Toxicology and Environmental Health. Part B Critical Reviews, 11(3-4), 322-344. doi: 10.1080/10937400701876194
Phillips, K. P., Foster, W. G., Leiss, W., Sahni, V., Karyakina, N., Turner, M. C... & Krewski, D. (2008). Assessing and managing risks arising from exposure to endocrine-active chemicals. Journal of Toxicology and Environmental Health. Part B Critical Reviews, 11(3-4), 351-372. doi: 10.1080/10937400701876657
Phillips, K. P., & Tanphaichitr N. (2008). Human exposure to endocrine disrupters and semen quality. Journal of Toxicology and Environmental Health. Part B, Critical Reviews, 11(3-4), 188-220. doi: 10.1080/10937400701873472
Salian, S., Doshi, T., & Vanage, G. (2009a). Impairment in protein expression profile of testicular steroid receptor coregulators in male rat offspring perinatally exposed to bisphenol A. Life Sciences, 85(1-2), 11-18. doi: 10.1016/ j.lfs.2009.04.005
Salian, S., Doshi, T., & Vanage, G. (2009b). Neonatal exposure of male rats to bisphenol A impairs fertility and expression of sertoli cell junctional proteins in the testis. Toxicology, 265(1- 2), 56-67. doi: 10.1016/j.tox.2009.09.012
Salian, S., Doshi, T., & Vanage, G. (2009c). Perinatal exposure of rats to bisphenol A affects the fertility of male off- spring. Life Sciences, 85(21- 22), 742-752. doi: 10.1016/ j.lfs.2009.10.004
Shin, J. H., Kim, T. S., Kang, I. H., Kang, T. S., Moon, H. J., & Han, S. Y. (2009). Effects of postnatal administration of diethylstilbestrol on puberty and thyroid function in male rats. Journal of Reproduction and Development, 55(5), 461-466. doi: 10.1262/jrd.20169
Tyl, R. W., Myers, C. B., Marr, M. C., Sloan, C. S., Castillo, N. P., Veselica, M. M.... & Waechter, J. M. Jr. (2008). Two-generation reproductive toxicity study of dietary bisphenol A in CD-1 (Swiss) mice. Toxicological Sciences, 104(2), 362 -384. doi: 10.1093/toxsci/kfn084
Tyshenko, M. G., Phillips, K. P., Mehta, M., Poirier, R., & Leiss W. (2008). Risk communication of endocrine-disrupting chemicals: improving knowledge translation and transfer. Journal of Toxicology and Environmental Health. Part B Critical Reviews, 11(3-4), 345-350. doi: 10.1080/10937400701876293
Volle, D. H., Decourteix, M., Garo, E., McNeilly, J., Fenichel, P., Auwerx, J... & Benahmed, M. (2009). The orphan nuclear receptor small heterodimer partner mediates male infertility induced by diethylstilbestrol in mice. The Journal of Clinical Investigation, 119(12), 3752-3764. doi: 10.1172/JCI38521
Warita, K., Sugawara, T., Yue, Z. P., Tsukahara, S., Mutoh, K., Hasegawa, Y... & Hoshi, N. (2006). Progression of the dose-related effects of estrogenic endocrine disruptors, an important factor in declining fertility, differs between the hypothalamo-pituitary axis and reproductive organs of male mice. Journal of Veterinary Medical Science, 68(12), 1257-1267. doi: 10.1292/jvms.68.1257
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