Exogenous oestradiol benzoate induces male mice azoospermia through modulation of oxidative stress and testicular metabolic cooperation

  • Authors:
    • Jianghua Le
    • Xiaocan Lei
    • Yanping Ren
    • Zhipeng Li
    • Haoyan Tu
    • Fangya Ding
    • Xiaodong Yi
    • Yi Zhou
    • Qingyou Liu
    • Shun Zhang
  • View Affiliations

  • Published online on: April 16, 2019     https://doi.org/10.3892/mmr.2019.10169
  • Pages: 4955-4963
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Abstract

In most cases, exogenous oestradiol benzoate (EB) inhibits spermatogenesis, however, the mechanism underlying this process has not been fully elucidated. The present study investigated the effect of EB on redox equilibrium and glycometabolism in mouse testes. Male Kunming mice were divided into 3 groups and injected with 0, 5 and 10 mg/kg EB, respectively. Histological analysis revealed no sperm and far fewer spermatogenic cells in the testes of EB‑treated mice. Additionally, transmission electron microscopy revealed that mitochondria in Sertoli cells were transformed to vacuoles with irregular cristae in the EB‑treated group. EB also significantly decreased the activities and mRNA expression of catalase, superoxide dismutase, and glutathione peroxidase and increased the activity of nitric oxide synthase and nitric oxide concentration in the testes compared with the control. These results indicated that oxidative damage was caused by EB treatment. With regard to glycometabolism, ATP content and activities of hexokinase and pyruvate kinase were significantly reduced in the EB‑treated group. Although glucose and pyruvate concentrations were significantly increased by EB treatment, levels of lactate, the main energy source of spermatogenic cells, were unchanged. Monocarboxylate transporter 2 (MCT2) and MCT4, which are responsible for lactate transportation, were downregulated by EB. In conclusion, the results of the present study indicated that azoospermia induced by EB in male mice was associated with oxidative damage and the disorder of testicular metabolic cooperation.

References

1 

O'Donnell L, Robertson KM, Jones ME and Simpson ER: Estrogen and spermatogenesis. Endocr Rev. 22:289–318. 2001. View Article : Google Scholar : PubMed/NCBI

2 

Pavlovich CP, King P, Goldstein M and Schlegel PN: Evidence of a treatable endocrinopathy in infertile men. J Urol. 165:837–841. 2001. View Article : Google Scholar : PubMed/NCBI

3 

Jensen TK, Toppari J, Keiding N and Skakkebaek NE: Do environmental estrogens contribute to the decline in male reproductive health? Clin Chem. 41:1896–1901. 1995.PubMed/NCBI

4 

Li X, Li H, Jia L, Li X and Rahman N: Oestrogen action and male fertility: Experimental and clinical findings. Cell Mol Life Sci. 72:3915–3930. 2015. View Article : Google Scholar : PubMed/NCBI

5 

Giwercman A: Estrogens and phytoestrogens in male infertility. Curr Opin Urol. 21:519–526. 2011. View Article : Google Scholar : PubMed/NCBI

6 

LaRocca J, Boyajian A, Brown C, Smith SD and Hixon M: Effects of in utero exposure to Bisphenol A or diethylstilbestrol on the adult male reproductive system. Birth Defects Res B Dev Reprod Toxicol. 92:526–533. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Vitku J, Sosvorova L, Chlupacova T, Hampl R, Hill M, Sobotka V, Heracek J, Bicikova M and Starka L: Differences in bisphenol A and estrogen levels in the plasma and seminal plasma of men with different degrees of infertility. Physiol Res. 64 (Suppl 2):S303–S311. 2015.PubMed/NCBI

8 

Chaki SP, Misro MM, Gautam DK, Kaushik M, Ghosh D and Chainy GB: Estradiol treatment induces testicular oxidative stress and germ cell apoptosis in rats. Apoptosis. 11:1427–1437. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Walker DM, Kermath BA, Woller MJ and Gore AC: Disruption of reproductive aging in female and male rats by gestational exposure to estrogenic endocrine disruptors. Endocrinology. 154:2129–2143. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Reilly MP, Weeks CD, Topper VY, Thompson LM, Crews D and Gore AC: The effects of prenatal PCBs on adult social behavior in rats. Horm Behav. 73:47–55. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Lei X, Cui K, Liu Q, Zhang H, Li Z, Huang B and Shi D: Exogenous estradiol benzoate induces spermatogenesis disorder through influencing apoptosis and oestrogen receptor signalling pathway. Reprod Domest Anim. 51:75–84. 2016. View Article : Google Scholar : PubMed/NCBI

12 

Cairns RA, Harris IS and Mak TW: Regulation of cancer cell metabolism. Nat Rev Cancer. 11:85–95. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Patnaik A, Locasale JW and Cantley LC: Cancer cell metabolism. Springer; US: 76. pp. 299–311. 2012

14 

Rato L, Alves MG, Socorro S, Duarte AI, Cavaco JE and Oliveira PF: Metabolic regulation is important for spermatogenesis. Nat Rev Urol. 9:330–338. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Oliveira PF and Alves MG: Sertoli Cell Metabolism and Spermatogenesis. Springerbriefs in Cell Biology. 1st. Springer International Publishing; pp. 982015

16 

Martins AD, Alves MG, Simões VL, Dias TR, Rato L, Moreira PI, Socorro S, Cavaco JE and Oliveira PF: Control of Sertoli cell metabolism by sex steroid hormones is mediated through modulation in glycolysis-related transporters and enzymes. Cell Tissue Res. 354:861–868. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Putz O, Schwartz CB, Kim S, LeBlanc GA, Cooper RL and Prins GS: Neonatal low- and high-dose exposure to estradiol benzoate in the male rat: I. Effects on the prostate gland. Biol Reprod. 65:1496–505. 2001. View Article : Google Scholar : PubMed/NCBI

18 

National Research Council (US) Institute for Laboratory Animal Research, . Guide for the Care and Use of Laboratory Animals. Astronomy & Astrophysics. 327:963–965. 2004.

19 

Gouyandeh J, Modaresi M, Mansouri S and Najafabadi FY: Long-term effects of betamethasone on epididymal tissue, epididymal sperm counts and fertility in male mice. J Chem Health Risks. 5:295–300. 2015.

20 

Clermont Y and Perey B: The stages of the cycle of the seminiferous epithelium of the rat: Practical definitions in PA-Schiff-hematoxylin and hematoxylin-eosin stained sections. Rev Can Biol. 16:451–462. 1957.PubMed/NCBI

21 

Nikolaidou B, Nouris C, Lazaridis A, Sampanis C and Doumas M: Diabetes mellitus and erectile dysfunction. Springer International Publishing; pp. 119–128. 2015

22 

Welborn JP, Davis MG, Ebers SD, Stodden GR, Hayashi K, Cheatwood JL, Rao MK and MacLean JA III: Rhox8 ablation in the sertoli cells using a tissue-specific RNAi approach results in impaired male fertility in mice. Biol Reprod. 93:82015. View Article : Google Scholar : PubMed/NCBI

23 

Sharpe RM: Environmental estrogens and male infertility. Pure App Chem. 70:1685–1701. 1998. View Article : Google Scholar

24 

Rochester JR: Bisphenol A and human health: A review of the literature. Reprod Toxicol. 42:132–155. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Rao MV and Chinoy NJ: Effect of oestradiol benzoate on reproductive organs and fertility in the male rat. Eur J Obstet Gynecol Reprod Biol. 15:189–198. 1983. View Article : Google Scholar : PubMed/NCBI

26 

Jin P, Wang X, Chang F, Bai Y, Li Y, Zhou R and Chen L: Low dose bisphenol A impairs spermatogenesis by suppressing reproductive hormone production and promoting germ cell apoptosis in adult rats. J Biomed Res. 27:135–144. 2013.PubMed/NCBI

27 

Samhan-Arias AK, Tyurina YY and Kagan VE: Lipid antioxidants: Free radical scavenging versus regulation of enzymatic lipid peroxidation. J Clin Biochem Nutr. 48:91–95. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Goc Z, Szaroma W, Kapusta E and Dziubek K: Protective effects of melatonin on the activity of SOD, CAT, GSH-Px and GSH content in organs of mice after administration of SNP. Chin J Physiol. 60:1–10. 2017. View Article : Google Scholar : PubMed/NCBI

29 

Omar SS, Aly RG and Badae NM: Vitamin E improves testicular damage in streptozocin-induced diabetic rats, via increasing vascular endothelial growth factor and poly(ADP-ribose) polymerase-1. Andrologia. 50:2018. View Article : Google Scholar : PubMed/NCBI

30 

Wiktorowska-Owczarek A, Berezińska M and Nowak JZ: PUFAs: Structures, metabolism and functions. Adv Clin Exp Med. 24:931–941. 2015. View Article : Google Scholar : PubMed/NCBI

31 

Schroeder F, Kier AB and Sweet WD: Role of polyunsaturated fatty acids and lipid peroxidation in LM fibroblast plasma membrane transbilayer structure. Arch Biochem Biophys. 276:55–64. 1990. View Article : Google Scholar : PubMed/NCBI

32 

Sakamoto M, Ueno T, Nakamura T, Sakata R, Hasimoto O, Torimura T and Sata M: Improvement of portal hypertension and hepatic blood flow in cirrhotic rats by oestrogen. Eur J Clin Invest. 35:220–225. 2015. View Article : Google Scholar

33 

Nevzati E, Shafighi M, Bakhtian KD, Treiber H, Fandino J and Fathi AR: Estrogen induces nitric oxide production via nitric oxide synthase activation in endothelial cells. Acta Neurochir Suppl. 120:141–145. 2015.PubMed/NCBI

34 

Al-Gubory KH: Mitochondria: Omega-3 in the route of mitochondrial reactive oxygen species. Int J Biochem Cell Biol. 44:1569–1573. 2012. View Article : Google Scholar : PubMed/NCBI

35 

Stepien KM, Heaton R, Rankin S, Murphy A, Bentley J, Sexton D and Hargreaves IP: Evidence of oxidative stress and secondary mitochondrial dysfunction in metabolic and non-metabolic disorders. J Clin Med. 6(pii): E712017. View Article : Google Scholar : PubMed/NCBI

36 

Liang H, Remmen HV, Frohlich V, Lechleiter J, Richardson A and Ran Q: GSH-Px4 protects mitochondrial ATP generation against oxidative damage. Biochem Biophys Res Commun. 356:893–898. 2007. View Article : Google Scholar : PubMed/NCBI

37 

Ke R, Xu Q, Li C, Luo L and Huang D: Mechanisms of AMPK in the maintenance of ATP balance during energy metabolism. Cell Biol Int. 42:384–392. 2018. View Article : Google Scholar : PubMed/NCBI

38 

Zhang J, Wang X, Vikash V, Ye Q, Wu D, Liu Y and Dong W: Ros and ros-mediated cellular signaling. Oxid Med Cell Longev. 2016:43509652016. View Article : Google Scholar : PubMed/NCBI

39 

Kishimoto A, Ishiguro-Oonuma T, Takahashi R, Maekawa M, Toshimori K, Watanabe M and Iwanaga T: Immunohistochemical localization of GLUT3, MCT1, and MCT2 in the testes of mice and rats: The use of different energy sources in spermatogenesis. Biomed Res. 36:225–234. 2015. View Article : Google Scholar : PubMed/NCBI

40 

D'Cruz SC, Jubendradass R and Mathur PP: Bisphenol A induces oxidative stress and decreases levels of insulin receptor substrate 2 and glucose transporter 8 in rat testis. Reprod Sci. 19:163–172. 2012. View Article : Google Scholar : PubMed/NCBI

41 

Rato L, Alves MG, Dias TR, Cavaco JE and Oliveira PF: Testicular metabolic reprogramming in neonatal streptozotocin-induced type 2 diabetic rats impairs glycolytic flux and promotes glycogen synthesis. J Diabetes Res. 2015:9731422015. View Article : Google Scholar : PubMed/NCBI

42 

Tavares RS, Portela JMD, Sousa MI, Mota PC, Ramalho-Santos J and Amaral S: High glucose levels affect spermatogenesis: An in vitro approach. Reprod Fertil Dev. 29:1369–1378. 2016. View Article : Google Scholar

43 

Oliveira PF and Alves MG: Modulation of sertoli cell metabolism. Springer International Publishing; pp. 57–71. 2015

44 

Oishi S: Effects of phthalic acid esters on testicular mitochondrial functions in the rat. Arch Toxicol. 64:143–147. 1990. View Article : Google Scholar : PubMed/NCBI

45 

Oliveira PF, Martins AD, Moreira AC, Cheng CY and Alves MG: The warburg effect revisited-lesson from the sertoli cell. Med Res Rev. 35:126–151. 2015. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
APA
Le, J., Lei, X., Ren, Y., Li, Z., Tu, H., Ding, F. ... Zhang, S. (2019). Exogenous oestradiol benzoate induces male mice azoospermia through modulation of oxidative stress and testicular metabolic cooperation. Molecular Medicine Reports, 19, 4955-4963. https://doi.org/10.3892/mmr.2019.10169
MLA
Le, J., Lei, X., Ren, Y., Li, Z., Tu, H., Ding, F., Yi, X., Zhou, Y., Liu, Q., Zhang, S."Exogenous oestradiol benzoate induces male mice azoospermia through modulation of oxidative stress and testicular metabolic cooperation". Molecular Medicine Reports 19.6 (2019): 4955-4963.
Chicago
Le, J., Lei, X., Ren, Y., Li, Z., Tu, H., Ding, F., Yi, X., Zhou, Y., Liu, Q., Zhang, S."Exogenous oestradiol benzoate induces male mice azoospermia through modulation of oxidative stress and testicular metabolic cooperation". Molecular Medicine Reports 19, no. 6 (2019): 4955-4963. https://doi.org/10.3892/mmr.2019.10169