Abstract
The diagnosis of azoospermia represents a major challenge to andrologists as this condition may occur despite normal spermatogenesis and genital tracts. Myeloid cell leukemia-1 (Mcl-1) is a member of the Bcl-2 family of proteins involved in regulation of apoptosis in various cell types. This study aimed to investigate the immunohistochemical expression of Mcl-1 in testicular biopsies of subjects with azoospermia. Eighty-six cases with azoospermia were obtained from 509 infertile patients admitted to the Andrology Unit of the Zagazig University Hospitals from January 2010 to December 2011. Biopsies were diagnosed and classified using H&E-stained slide sections. The specimens were subjected to immunohistochemical staining for Mcl-1 and examined through light microscopy. Forty-five cases of maturation arrest (25 at spermatids and 20 at the spermatocytes), 31 cases of hypospermatogenesis (20 moderate and 11 severe), 5 cases of Sertoli cell-only syndrome, 2 cases of basement membrane hyalinization, and 1 case of tubular and peritubular sclerosis were observed. Normal spermatogenesis was detected in 2 cases. A strong positive immunoreaction in Leydig cells was observed among all investigated specimens. A moderate reaction was detected in spermatocytes and spermatozoa in cases of normal spermatogenesis and hypospermatogenesis, but a negative reaction was detected in cases of maturation arrest and germ cell aplasia. Apoptosis was found to be associated with decreased rate of spermatogenesis. High apoptosis rates may result in azoospermia, which can occur despite normal spermatogenesis and absence of duct obstruction.
Similar content being viewed by others
References
Hetts SW. To die or not to die: an overview of apoptosis and its role in disease. JAMA 1998; 279(4): 300–307
Kerr JFR, Winterford CM, Harmon BV. Apoptosis. Its significance in cancer and cancer therapy. Cancer 1994; 73(8): 2013–2026
Brinkworth MH, Weinbauer GF, Bergmann M, Nieschlag E. Apoptosis as a mechanism of germ cell loss in elderly men. Int J Androl 1997; 20(4): 222–228
Dunkel L, Hirvonen V, Erkkilä K. Clinical aspects of male germ cell apoptosis during testis development and spermatogenesis. Cell Death Differ 1997; 4(3): 171–179
Hikim AP, Wang C, Lue Y, Johnson L, Wang XH, Swerdloff RS. Spontaneous germ cell apoptosis in humans: evidence for ethnic differences in the susceptibility of germ cells to programmed cell death. J Clin Endocrinol Metab 1998; 83(1): 152–156
Sinha Hikim AP, Swerdloff RS. Hormonal and genetic control of germ cell apoptosis in the testis. Rev Reprod 1999; 4(1): 38–47
Opferman JT, Iwasaki H, Ong CC, Suh H, Mizuno S, Akashi K, Korsmeyer SJ. Obligate role of anti-apoptotic MCL-1 in the survival of hematopoietic stem cells. Science 2005; 307(5712): 1101–1104
Lipshultz LI, Howards SS. Evaluation of the subfertile male. In: Lipshultz LI, Howards SS. Infertility in the Male. 3rd ed. St. Louis: Mosby-Year Book, Inc., 1997: 173–193
Coburn M, Kim ED, Wheeler TM. Testicular biopsy in male infertility evaluation. In: Lipshultz LI, Howards SS. Infertility in the Male. 3rd ed. St. Louis: Mosby-Year Book, Inc., 1997: 219–248
Kovacs G. Assessment of the male partner. In: Kovacs G. The Subfertility Handbook: a Clinician’s Guide. Cambridge: Cambridge University Press, 2010: 54–59
Boenisch T, Farmilo AJ, Stead RH, Key M, Welcher R, Harvey R, Atwood KN. Hand Book Immunochemical Staining Methods, 3rd ed. Carpinteria, California USA: DAKO Corporation, 2001: 1–62
Kukner A, Oner J, Oner H, Ozan E. Effect of vitamin E on expression of Appoptosis Related Proteins in Immobilized Rat testes. J Anim Vet Adv 2010; 9(1): 180–185
Sugiyama N, Obinata M, Matsui Y. Bcl-2 inhibits apoptosis of spermatogonia and growth of spermatogonial stem cells in a cellintrinsic manner. Mol Reprod Dev 2001; 58(1): 30–38
Rinkenberger JL, Horning S, Klocke B, Roth K, Korsmeyer SJ. Mcl-1 deficiency results in peri-implantation embryonic lethality. Genes Dev 2000; 14(1): 23–27
Yang T, Buchan HL, Townsend KJ, Craig RW. MCL-1, a member of the BLC-2 family, is induced rapidly in response to signals for cell differentiation or death, but not to signals for cell proliferation. J Cell Physiol 1996; 166(3): 523–536
Oldereid NB, Angelis PD, Wiger R, Clausen OP. Expression of Bcl-2 family proteins and spontaneous apoptosis in normal human testis. Mol Hum Reprod 2001; 7(5): 403–408
El-Fackahany HM, Sakkas D. Abortive apoptosis and sperm chromatin damage. In: Zini A, Agarwell A. Sperm Chromatin: Biological and Clinical Applications in Male Infertility. New York: Springer-Verlag New York, 2011
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hegazy, R., Hegazy, A., Ammar, M. et al. Immunohistochemical measurement and expression of Mcl-1 in infertile testes. Front. Med. 9, 361–367 (2015). https://doi.org/10.1007/s11684-015-0395-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11684-015-0395-x