Asian-Australasian Journal of Animal Sciences

Asian Australasian Association of Animal Production Societies (아세아태평양축산학회)
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Hemicastration induced spermatogenesis-related DNA methylation and gene expression changes in mice testis

  • Wang, Yixin (Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University) ;
  • Jin, Long (Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University) ;
  • Ma, Jideng (Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University) ;
  • Chen, Li (Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University) ;
  • Fu, Yuhua (Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University) ;
  • Long, Keren (Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University) ;
  • Hu, Silu (Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University) ;
  • Song, Yang (Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University) ;
  • Shang, Dazhi (Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University) ;
  • Tang, Qianzi (Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University) ;
  • Wang, Xun (Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University) ;
  • Li, Xuewei (Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University) ;
  • Li, Mingzhou (Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University)
  • Received : 2017.07.10
  • Accepted : 2017.09.21
  • Published : 2018.02.01
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Abstract

Objective: Hemicastration is a unilateral orchiectomy to remove an injured testis, which can induce hormonal changes and compensatory hypertrophy of the remaining testis, and may influence spermatogenesis. However, the underlying molecular mechanisms are poorly understood. Here, we investigated the impact of hemicastration on remaining testicular function. Methods: Prepubertal mice (age 24 days) were hemicastrated, and their growth was monitored until they reached physical maturity (age 72 days). Subsequently, we determined testis DNA methylation patterns using reduced representation bisulfite sequencing of normal and hemicastrated mice. Moreover, we profiled the testicular gene expression patterns by RNA sequencing (RNA-seq) to examine whether methylation changes affected gene expression in hemicastrated mice. Results: Hemicastration did not significantly affect growth or testosterone (p>0.05) compared with control. The genome-wide DNA methylation pattern of remaining testis suggested that substantial genes harbored differentially methylated regions (1,139) in gene bodies, which were enriched in process of protein binding and cell adhesion. Moreover, RNA-seq results indicated that 46 differentially expressed genes (DEGs) involved in meiotic cell cycle, synaptonemal complex assembly and spermatogenesis were upregulated in the hemicastration group, while 197 DEGs were downregulated, which were related to arachidonic acid metabolism. Integrative analysis revealed that proteasome 26S subunit ATPase 3 interacting protein gene, which encodes a protein crucial for homologous recombination in spermatocytes, exhibited promoter hypomethylation and higher expression level in hemicastrated mice. Conclusion: Global profiling of DNA methylation and gene expression demonstrated that hemicastration-induced compensatory response maintained normal growth and testicular morphological structure in mice.

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References

  1. Barnes MA, Kazmer GW, Boockfor FR, et al. Testosterone, luteinizing hormone, follicle stimulating hormone, and prolactin response to unilateral castration in prepubertal Holstein bulls. Theriogenology 1983;19:635-46. https://doi.org/10.1016/0093-691X(83)90104-8
  2. Berger T, Conley A. Reduced endogenous estrogen and hemicastration interact synergistically to increase porcine sertoli cell proliferation. Biol Reprod 2014;90:114.
  3. Jacobsen KD, Theodorsen L, Fossa SD. Spermatogenesis after unilateral orchiectomy for testicular cancer in patients following surveillance policy. J Urol 2001;165:93-6. https://doi.org/10.1097/00005392-200101000-00023
  4. Naoman UT, Taha MB. Effect of hemi-castration on testicular growth and seminal characteristics of Iraqi male goats. Iraqi J Vet Sci 2010;24:71(En)-4(En). https://doi.org/10.33899/ijvs.2010.5589
  5. Luo Q, Li Z, Huang X, et al. Lycium barbarum polysaccharides: Protective effects against heat-induced damage of rat testes and $H_2O_2$-induced DNA damage in mouse testicular cells and beneficial effect on sexual behavior and reproductive function of hemicastrated rats. Life Sci 2006;79:613-21. https://doi.org/10.1016/j.lfs.2006.02.012
  6. Reizel Y, Spiro A, Sabag O, et al. Gender-specific postnatal demethylation and establishment of epigenetic memory. Genes Dev 2015;29:923-33. https://doi.org/10.1101/gad.259309.115
  7. Auger CJ, Coss D, Auger AP, Forbeslorman RM. Epigenetic control of vasopressin expression is maintained by steroid hormones in the adult male rat brain. Proc Natl Acad Sci USA 2011;108:4242-7. https://doi.org/10.1073/pnas.1100314108
  8. Ghahramani NM, Ngun TC, Chen PY, et al. The effects of perinatal testosterone exposure on the DNA methylome of the mouse brain are late-emerging. Biol Sex Differ 2014;5:8. https://doi.org/10.1186/2042-6410-5-8
  9. Cui LB, Zhou XY, Zhao ZJ, et al. The Kunming mouse: as a model for age-related decline in female fertility in human. Zygote 2013;21:367-76. https://doi.org/10.1017/S0967199412000123
  10. Frankel AI, Chapman JC, Cook B. Testes are asymmetric in the testicular hemicastration response of the male rat. J Endocrinol 1989;122:485-8. https://doi.org/10.1677/joe.0.1220485
  11. Gu H, Smith ZD, Bock C, et al. Preparation of reduced representation bisulfite sequencing libraries for genome-scale DNA methylation profiling. Nat Protoc 2011;6:468-81. https://doi.org/10.1038/nprot.2010.190
  12. Wang H, Wang Q, Zhao XF, et al. Cypermethrin exposure during puberty disrupts testosterone synthesis via downregulating StAR in mouse testes. Arch Toxicol 2010;84:53-61. https://doi.org/10.1007/s00204-009-0479-y
  13. Bello AA, Adama TZ. Studies on body weight and linear body measurements of castrates and non-castrate savannah brown goats. Asian J Anim Sci 2003;6:140-6.
  14. Mccormick JD, Valdez R, Rakestraw PC, et al. Effect of surgical technique for unilateral orchiectomy on subsequent testicular function in Miniature Horse stallions. Equine Vet J Suppl 2012;44(Suppl):100-4.
  15. Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet 2012;13:484-92. https://doi.org/10.1038/nrg3230
  16. Lie PP, Mruk DD, Lee WM, Cheng CY. Cytoskeletal dynamics and spermatogenesis. Philos Trans R Soc Lond B Biol Sci 2010;365(1546):1581-92. https://doi.org/10.1098/rstb.2009.0261
  17. Saitou M, Furuse M, Sasaki H, et al. Complex phenotype of mice lacking occludin, a component of tight junction strands. Mol Biol Cell 2000;11:4131-42.
  18. Korhonen HM, Yadav RP, Da Ros M, et al. DICER regulates the formation and maintenance of cell-cell junctions in the mouse seminiferous epithelium. Biol Reprod 2015;93:139.
  19. Kouznetsova A, Novak I, Jessberger R, Hoog C. SYCP2 and SYCP3 are required for cohesin core integrity at diplotene but not for centromere cohesion at the first meiotic division. J Cell Sci 2005;118:2271-8. https://doi.org/10.1242/jcs.02362
  20. Daniel K, Lange J, Hached K, et al. Meiotic homologous chromosome alignment and its surveillance are controlled by mouse HORMAD1. Nat Cell Biol 2011;13:599-610. https://doi.org/10.1038/ncb2213
  21. Li W, Tang W, Teves ME, et al. A MEIG1/PACRG complex in the manchette is essential for building the sperm flagella. Development 2015;142:921-30. https://doi.org/10.1242/dev.119834
  22. Salzberg Y, Eldar T, Karminsky OD, et al. Meig1 deficiency causes a severe defect in mouse spermatogenesis. Dev Biol 2010;338:158-67. https://doi.org/10.1016/j.ydbio.2009.11.028
  23. Mruk DD, Cheng CY. Sertoli-sertoli and sertoli-germ cell interactions and their significance in germ cell movement in the seminiferous epithelium during spermatogenesis. Endocr Rev 2004;25:747-806. https://doi.org/10.1210/er.2003-0022
  24. Vihko KK, Toppari J, Parvinen M. Stage-specific regulation of plasminogen activator secretion in the rat seminiferous epithelium. Endocrinology 1987;120:142-5.
  25. Frungieri MB, Calandra RS, Mayerhofer A, Matzkin ME. Cyclooxygenase and prostaglandins in somatic cell populations of the testis. Reproduction 2015;149:R169-80. https://doi.org/10.1530/REP-14-0392
  26. Aaronson DS, Iman R, Walsh TJ, Kurhanewicz J, Turek PJ. A novel application of 1H magnetic resonance spectroscopy: non-invasive identification of spermatogenesis in men with non-obstructive azoospermia. Hum Reprod 2010;25:847-52.
  27. Kang HA, Shin HC, Kalantzi AS, et al. Crystal structure of Hop2–Mnd1 and mechanistic insights into its role in meiotic recombination. Nucleic Acids Res 2015;43:3841-56. https://doi.org/10.1093/nar/gkv172
  28. Pezza RJ, Voloshin ON, Volodin AA, et al. The dual role of HOP2 in mammalian meiotic homologous recombination. Nucleic Acids Res 2014;42:2346-57. https://doi.org/10.1093/nar/gkt1234
  29. Petukhova GV, Romanienko PJ, Camerini-Otero RD. The Hop2 protein has a direct role in promoting interhomolog interactions during mouse meiosis. Dev Cell 2003;5:927-36. https://doi.org/10.1016/S1534-5807(03)00369-1
  30. Yamaguchi S, Hong K, Liu R, et al. Tet1 controls meiosis by regulating meiotic gene expression. Nature 2012;492:443-7. https://doi.org/10.1038/nature11709