Herpes Simplex Virus Type I Infection of Mice Testis and Effect on Fertility

Authors: Victor A. Naumenko, Yuriy A. Tyulenev, Alla A. Kushch

Abstract:

The objective of current issue was to develop a model of testicular herpes simplex virus (HSV) type I infection for assessment of viral effect on fertility. 56 male mice were inoculated intraperitoneally with different concentrations of HSV on 8 day post partum. It was revealed that the optimal dose was 100 plaque forming units per mice as it provided testicular infection in 100% of survivors. HSV proteins were detected both in somatic and germ cells (spermatogonia, spermatocytes, spermatides). Although DNA load in testis was descending from 3 to 28 days post infection only 12.5% of infected males had offspring after mating with uninfected females comparing to 87.5% in control (p=0.012). These results are the first direct evidence for HSV impact in male sterility. Prepuberal mice appeared to be a suitable model for investigation of pathogenesis of virus-associated fertility disorders.

Keywords: Herpes simplex virus type I, male fertility, prepuberal mice, spermatogenesis.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1056128

References:

[1] N. Kapranos, E. Petrakou, C. Anastasiadou and D. Kotronias, "Detection of herpes simplex virus, cytomegalovirus, and Epstein-Barr virus in the semen of men attending an infertility clinic," Fertil Steril., vol. 79, suppl. 79, pp. 1566-1570, Jun 2003.
[2] N. el Borai, M. Inoue, C. Lefevre, E. N. Naumova, B. Sato and M. Yamamura, "Detection of herpes simplex DNA in semen and menstrual blood of individuals attending an infertility clinic," J Obstet Gynaecol Res., vol. 23, pp. 17-24, Feb 1997.
[3] D. Kotronias and N. Kapranos, "Detection of herpes simplex virus DNA in human spermatozoa by in situ hybridization technique," In Vivo., vol. 12, pp 391-394, Jul-Aug 1998.
[4] G. Bezold, J.A. Politch, N.B. Kiviat, J. M. Kuypers, H. Wolff and D. J. Anderson, "Prevalence of sexually transmissible pathogens in semen from asymptomatic male infertility patients with and without leukocytospermia," Fertil Steril., vol. 87, pp. 1087-1097, May 2007.
[5] R. R. Klimova, E.V. Chichev, V. A. Naumenko, Z. S. Gadzhieva, A. S. Tsibisov, et al., "Herpes simplex virus and cytomegalovirus in male ejaculate: herpes simplex virus is more frequently encountered in idiopathic infertility and correlates with the reduction in sperm parameters," Vopr virusol., vol. 57, pp. 27-31, Jan 2010.
[6] E. N. Bocharova, L. E. Zavalishina, E. E. Bragina, R. R. Klimova, Y. K. Gusak, et al., "Detection of herpes simplex virus genomic DNA in spermatozoa of patients with fertility disorders by in situ hybridization," Dokl Biol Sci., vol. 412, pp. 82-86, Jan 2007.
[7] G. Bezold, A. Schuster-Grusser, M. Lange, H. Gall, H. Wolff, et al., "Prevalence of human herpesvirus types 1-8 in the semen of infertility patients and correlation with semen parameters," Fertil. Steril., vol. 76, pp. 416-418, Aug 2001.
[8] E. Neofytou, G. Sourvinos, M. Asmarianaki, D. A. Spandidos, A. Makrigiannakis, "Prevalence of human herpes virus types 1-7 in the semen of men attending an infertility clinic and correlation with semen parameters, " Fertil. Steril., vol. 91, pp. 2487-2494, Jun 2009.
[9] A. R. Bellve, J. C. Cavicchia, C. F. Millete, D. A. O'Brien, Y. M. Bhatnagar, et al., "Spermatogenic cells of the prepuberal mouse. Isolation and morphological characterization," J. Cell Biol., vol. 74, pp. 68-85, Jul 1977.
[10] S. V. Gribencha, E. E. Bragina, R. A. Abdumalikov, E. N. Bocharova, L. F. Kurilo, "Detection of type 2 herpes simplex virus in cells of spermatogenic epithelium in infected testis of guinea pigs", Bull. Exp. Biol. Med., vol. 144, pp. 73-76, Jul 2007.
[11] L. Tebourbi, A. M. Courtot, R. Duchateau, A. Loeuillet, J. Testart, et al., "Experimental inoculation of male mice with murine cytomegalovirus and effect on offspring," Hum. Reprod., vol. 16, pp. 2041-2049, Oct 2001.
[12] J. S. Burgos, C. Ramirez, I. Sastre, J. M. Alfaro, and F. Valdivieso, "Herpes simplex virus type 1 infection via the bloodstream with apolipoprotein E dependence in the gonads is influenced by gender, " J. Virol., vol. 79, pp. 1605-1612, Feb 2005.
[13] J. S. Burgos, C. Ramirez, F. Guzman-Sanchez, J. M. Alfaro, I. Sastre, et al., "Hematogenous vertical transmission of herpes simplex virus type 1 in mice," J. Virol., vol. 80, no. 6, pp. 2823-2831, Mar 2006.
[14] C. S. Miller, R. J. Danaher, R. J. Jacob, "Molecular aspects of herpes simplex virus I latency, reactivation, and recurrence," Crit Rev Oral Biol Med., vol. 9, no. 4, pp. 541-562, Jan 1998.
[15] C. Shaha, R. Tripathi, D. P. Mishra, "Male germ cell apoptosis: regulation and biology," Philos Trans R Soc Lond B Biol Sci., vol. 365, pp. 1501-1515, May 2010.
[16] M. Aubert, J. O'Toole, J. A. Blaho, "Induction and prevention of apoptosis in human HEp-2 cells by herpes simplex virus type 1," J Virol., vol. 73, no. 12, pp. 10359-10370, Dec 1999.
[17] A. P. Satie, S. Mazaud-Guittot, I. Seif, D. Mahé, Z. He, et al., "Excess type I interferon signaling in the mouse seminiferous tubules leads to germ cell loss and sterility," J Biol Chem., vol. 286, no. 26, pp. 23280- 23295, Jul 2011.
[18] O. Sarkar, J. Bahrainwala, S. Chandrasekaran, S. Kothari, P. P. Mathur, et al., "Impact of inflammation on male fertility," Front Biosci (Elite Ed)., vol. 1, no. 3, pp. 89-95, Jan 2011.
[19] S. Fountain, M. K. Holland, L. A. Hinds, P. A. Janssens, P. J. Kerr, "Interstitial orchitis with impaired steroidogenesis and spermatogenesis in the testes of rabbits infected with an attenuated strain of myxoma virus," J Reprod Fertil., vol. 110, no. 1, pp. 161-169, May 1997.