Tang WENHAO, Liu DE-FENG, Hong KAI, Zhao LIAN-MING, Mao JIA-MING, Zhuang XIN-JIE, Ma LU-LIN, Jiang HUI

miRNA-mediated regulation of heat shock proteins in human ejaculated spermatozoa

Background/aim: Heat shock proteins (HSPs) are expressed in human spermatozoa and play a role in sperm function. MicroRNAs (miRNAs) regulate gene expression, and the possible involvement of miRNAs in the regulation of HSP gene expression in sperm was investigated in this study. Materials and methods: miRNAs differentially expressed in 8 copies of an oligoasthenozoospermic semen group (OA) were identified by comparison with a normal male semen control group (NC) using microarray technology. Potential targets of HSP proteins among the differentially expressed miRNAs were further investigated. Results: HSP40, HSP60, HSP70, and HSP90 were all found to be expressed in human ejaculated spermatozoa. A total of 32 miRNAs showed significant differences in expression between the OA and NC groups. Ten of these miRNAs encoded potential targets of HSPs. Conclusion: These results show that specific miRNAs are expressed in human ejaculated spermatozoa. These miRNAs appear to be involved in regulating the expression of HSP40, HSP70, and HSP90, and this in turn affects sperm function.

Anahtar Kelimeler:

Heat-shock proteins, microRNAs, microarray, spermatozoa, infertility

miRNA-mediated regulation of heat shock proteins in human ejaculated spermatozoa

Keywords:

Heat-shock proteins, microRNAs, microarray, spermatozoa, infertility,

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Volpe S, Galeati G, Bernardini C, Tamanini C, Mari G, Zambelli D, Seren E, Spinaci M. Comparative immunolocalization of heat shock proteins (Hsp)-60, -70, -90 in boar, stallion, dog and cat spermatozoa. Reprod Domest Anim 2008; 43: 385–392. 2. Lachance C, Fortier M, Thimon V, Sullivan R, Bailey JL, Leclerc P. Localization of Hsp60 and Grp78 in the human testis, epididymis and mature spermatozoa. Int J Androl 2010; 33: 33–44.
Erata GO, Kocak Toker N, Durlanik O, Kadioglu A, Aktan G, Aykac Toker G. The role of heat shock protein 70 (Hsp 70) in male infertility: is it a line of defense against sperm DNA fragmentation? Fertil Steril 2008; 90: 322–327.
Miller D. Analysis and significance of messenger RNA in human ejaculated spermatozoa. Mol Reprod Dev 2000; 56: 259–264.
Ecroyd H, Jones RC, Aitken RJ. Tyrosine phosphorylation of HSP-90 during mammalian sperm capacitation. Biol Reprod 2003; 69: 1801–1807.
Doiguchi M, Kaneko T, Urasoko A, Nishitani H, Iida H. Identification of a heat-shock protein Hsp40, DjB1, as an acrosome- and a tail-associated component in rodent spermatozoa. Mol Reprod Dev 2007; 74: 223–232.
Hu Y, Zhou Z, Huang X, Xu M, Lu L, Xu Z, Li J, Sha J. Expression of a novel DnaJA1 alternative splicing in human testis and sperm. Int J Androl 2004; 27: 343–349.
Nonoguchi K, Tokuchi H, Okuno H, Watanabe H, Egawa H, Saito K, Oqawa O, Fujita J. Expression of Apg-1, a member of the Hsp110 family, in the human testis and sperm. Int J Urol 2001; 8: 308–314. 9. Beere HM. “The stress of dying”: the role of heat shock proteins in the regulation of apoptosis. J Cell Sci 2004; 117: 2641–2651.
Kotaja N. MicroRNAs and spermatogenesis. Fertil Steril 2014; 101: 1552–1562.
Gapp K, Jawaid A, Sarkies P, Bohacek J, Pelczar P, Prados J, Farinelli L, Miska E, Mansuy IM. Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice. Nat Neurosci 2014; 17: 667–669.
Wu W, Hu Z, Qin Y, Dong J, Dai J, Lu C, Zhang W, Shen H, Xia Y, Wang X. Seminal plasma microRNAs: potential biomarkers for spermatogenesis status. Mol Hum Reprod 2012; 18: 489– 497.
Contessi S, Comelli M, Cmet S, Lippe G, Mavelli I. IF(1) distribution in HepG2 cells in relation to ecto-F(0)F(1) ATPsynthase and calmodulin. J Bioenerg Biomembr 2007; 39: 291–300.
Salas-Huetos A, Blanco J, Vidal F, Mercader JM, Garrido N, Anton E. New insights into the expression profile and function of micro-ribonucleic acid in human spermatozoa. Fertil Steril 2014; 102: 213–222.
Adams BD, Furneaux H, White BA. The micro-ribonucleic acid (miRNA) miR-206 targets the human estrogen receptor-α (ERα) and represses ERα messenger RNA and protein expression in breast cancer cell lines. Mol Endocrinol 2007; 21: 1132–1147.
Son WY, Han CT, Hwang SH, Lee JH, Kim S, Kim YC. Repression of hspA2 messenger RNA in human testes with abnormal spermatogenesis. Fertil Steril 2000; 73: 1138–1144.
Austin CR. Activation and the correlation between male and female elements in fertilization. Nature 1951; 168: 558–559.
Martinez-Prado E, Camejo Bermudez MI. Expression of IL-6, IL-8, TNF-alpha, IL-10, HSP-60, anti-HSP-60 antibodies, and anti-sperm antibodies, in semen of men with leukocytes and/ or bacteria. Am J Reprod Immunol 2010; 63: 233–243.
Schlesinger MJ. Heat shock proteins. J Biol Chem 1990; 265: 12111–12114.
Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, Horvitz HR, Ruvkun G. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 2000; 403: 901–906.
Huang SY, Kuo YH, Tsou HL, Lee YP, King YT, Huang HC, Yang PC, Lee WC. The decline of porcine sperm motility by geldanamycin, a specific inhibitor of heat-shock protein 90 (HSP90). Theriogenology 2000; 53: 1177–1184.
Christians ES, Zhou Q, Renard J, Benjamin IJ. Heat shock proteins in mammalian development. Semin Cell Dev Biol 2003; 14: 283–290.
Mosser DD, Caron AW, Bourget L, Denis-Larose C, Massie B. Role of the human heat shock protein hsp70 in protection against stress-induced apoptosis. Mol Cell Biol 1997; 17: 5317– 5327.
Georgopoulos C, Welch WJ. Role of the major heat shock proteins as molecular chaperones. Annu Rev Cell Biol 1993; 9: 601–634.
Ohtsuka K, Hata M. Mammalian HSP40/DNAJ homologs: cloning of novel cDNAs and a proposal for their classification and nomenclature. Cell Stress Chaperones 2000; 5: 98–112.
Zhou X, Kudo A, Kawakami H, Hirano H. Immunohistochemical localization of androgen receptor in mouse testicular germ cells during fetal and postnatal development. Anat Rec 1996; 245: 509–518.
Terada K, Mori M. Human DnaJ homologs dj2 and dj3, and bag-1 are positive cochaperones of hsc70. J Biol Chem 2000; 275: 24728–24734.
Guan J, Yuan L. A heat-shock protein 40, DNAJB13, is an axoneme-associated component in mouse spermatozoa. Mol Reprod Dev 2008; 75: 1379–1386.
Banecki B, Liberek K, Wall D, Wawrzynow A, Georgopoulos C, Bertoli E, Tanfani F, Zylicz M. Structure-function analysis of the zinc finger region of the DnaJ molecular chaperone. J Biol Chem 1996; 271: 14840–14848.