Abstract
The importance of sperm DNA integrity is hard to overestimate since the quality of the genetic material in a sperm population is the key point for successful fertilization, the embryonic and subsequent development of offspring, and, therefore, the male reproductive potential. Apoptosis is essential for male gametes in the period from the time of appearance of the gonadal anlagen in the embryo to the moment of fertilization. This mechanism of programmed cell death is necessary to maintain the appropriate ratio between the germ cells and the Sertoli cells during prenatal development. The damaged cells are removed from the testicles in the adult specimens by the apoptosis pathway. A range of unfavorable effects can intensify this process. In addition, mature spermatozoa undergo apoptosis and subsequent phagocytosis in the female reproductive tract in order to prevent the inflammatory response triggered by the dead gamete destruction. The impaired process of apoptosis may cause developmental abnormalities in male gametes, infertility, and fertilization of oocyte by sperm with DNA damage followed by subsequent offspring death. Therefore, recent studies show that apoptosis is one of the main causes of sperm DNA fragmentation, which tends to become a significant problem under conditions for the widespread use of assisted reproductive technologies.
Similar content being viewed by others
REFERENCES
Agger, K., Santoni-Rugiu, E., Holmberg, C., et al., Conditional E2F1 activation in transgenic mice causes testicular atrophy and dysplasia mimicking human cis, Oncogene, 2005, vol. 24, pp. 780–789.
Aitken, R.J., The capacitation-apoptosis highway: oxysterols and mammalian sperm function, Biol. Reprod., 2011, vol. 85, pp. 9–12.
Aitken, R.J., Reactive oxygen species as mediators of sperm capacitation and pathological damage, Mol. Reprod. Dev., 2017, vol. 84, no. 10, pp. 1039–1052.
Aitken, R.J. and Koppers, A.J., Apoptosis and DNA damage in human spermatozoa, Asian J. Androl., 2011, vol. 13, pp. 36–42.
Aitken, R.J., Findlay, J.K., Hutt, K.J., et al., Apoptosis in the germ line, Reproduction, 2011, vol. 141, pp. 139–150.
Aitken, R.J., Whiting, S., De Iuliis, G.N., et al., Electrophilic aldehydes generated by sperm metabolism activate mitochondrial reactive oxygen species generation and apoptosis by targeting succinate dehydrogenase, J. Biol. Chem., 2012, vol. 287, pp. 33048–33060.
Aitken, R.J., Baker, M.A., and Nixon, B., Are sperm capacitation and apoptosis the opposite ends of a continuum driven by oxidative stress?, Asian J. Androl., 2015, vol. 17, pp. 633–639.
Allan, D.J., Harmon, B.V., and Kerr, J.F.R., Cell death in spermatogenesis, in Perspectives on Mammalian Cell Death, Oxford: Univ. Press, London, 1987, pp. 229–258.
Amaral, A., Lourenco, B., Marques, M., et al., Mitochondria functionality and sperm quality, Reproduction, 2013, vol. 146, no. 5, pp. 163–174.
Anzar, M., He, L., Buhr, M.M., et al., Sperm apoptosis in fresh and cryopreserved bull semen detected by flow cytometry and its relationship with fertility, Biol. Reprod., 2002, vol. 66, pp. 354–360.
Baker, M.A., Weinberg, A., Hetherington, L., et al., Defining the mechanisms by which the reactive oxygen species by-product, 4-hydroxynonenal, affects human sperm cell function, Biol. Reprod., 2015, vol. 92, no. 4, p. 108.
Bartke, A., Apoptosis of male germ cells, a generalized or a cell type-specific phenomenon?, Endocrinology, 1995, vol. 136, no. 1, pp. 3–4.
Bejarano, I., Lozano, G.M., Ortiz, A., et al., Caspase 3 activation in human spermatozoa in response to hydrogen peroxide and progesterone, Fertil. Steril., 2008, vol. 90, pp. 1340–1347.
Boitseva, E.N., Denisenko, V.Yu., and Kuz’mina, T.I., Evaluation of indicators of postejaculation maturation of spermatozoa of Bos taurus using a chlortetracycline test, Russ. J. Dev. Biol., 2015, vol. 46, no. 6, pp. 362–367.
Boitseva, E.N., Bychkova, N.V., and Kuz’mina, T.I., Influence of highly dispersed silica nanoparticles on the apoptosis of Bos taurus sperm, Tsitologiya, 2017, vol. 59, no. 5, pp. 375–380.
Branco, C.S., Garcez, M.E., Pasqualotto, F.F., et al., Resveratrol and ascorbic acid prevent DNA damage induced by cryopreservation in human semen, Cryobiology, 2010, vol. 60, no. 2, pp. 235–237.
Cai, J. and Jones, D.P., Superoxide in apoptosis. Mitochondrial generation triggered by cytochrome c loss, J. Biol. Chem., 1998, vol. 273, pp. 11401–11404.
Chimento, A., Sirianni, R., Delalande, C., et al., 17 beta-estradiol activates rapid signaling pathways involved in rat pachytene spermatocytes apoptosis through GPR30 and ER alpha, Mol. Cell Endocrinol., 2010, vol. 320, pp. 136–144.
Correia, J., Michelangeli, F., and Publicover, S., Regulation and roles of Ca2+ stores in human sperm, Reproduction, 2015, vol. 150, no. 2, pp. R65–R76.
Dogan, S., Mason, M.C., Govindaraju, A., et al., Interrelationships between apoptosis and fertility in bull sperm, J. Reprod. Dev., 2013, vol. 59, no. 1, pp. 18–26.
Gallardo Bolaños, J.M., Miró Morán, Á., Balao da Silva, C.M., et al., Autophagy and apoptosis have a role in the survival or death of stallion spermatozoa during conservation in refrigeration, PLoS One, 2012, vol. 7, no. 1. e30688.
Grad, I., Cederroth, C.R., Walicki, J., et al., The molecular chaperone Hsp90ais required for meiotic progression of spermatocytes beyond pachytene in the mouse, PLoS One, 2010, vol. 5, no. 12. e15770.
Grunewald, S., Kriegel, C., Baumann, T., et al., Interactions between apoptotic signal transduction and capacitation in human spermatozoa, Hum. Reprod., 2009, vol. 24, no. 9, pp. 2071–2078.
De Iuliis, G.N., Thomson, L.K., Mitchell, L.A., et al., DNA damage in human spermatozoa is highly correlated with the efficiency of chromatin remodeling and the formation of 8-hydroxy-2'-deoxyguanosine, a marker of oxidative stress, Biol. Reprod., 2009, vol. 81, pp. 517–524.
Koppers, A.J., Mitchell, L.A., Wang, P., et al., Phosphoinositide 3-kinase signalling pathway involvement in a truncated apoptotic cascade associated with motility loss and oxidative DNA damage in human spermatozoa, Biochem. J., 2011, vol. 436, pp. 687–698.
Kosir, R., Juvan, P., Perse, M., et al., Novel insights into the downstream pathways and targets controlled by transcription factors CREM in the testis, PLoS One, 2012, vol. 7, no. 2. e31798.
Kostro, K., Krakowski, L., Lisiecka, U., et al., Flow cytometric evaluation of sperm apoptosis in semen of silver foxes in the breeding period, Anim. Reprod. Sci., 2014, vol. 144, pp. 54–58.
Krakowski, L., Obara, J., Wachocka, A., et al., Assessment of extent of apoptosis and DNA defragmentation in chilled semen of stallions during the breeding season, Reprod. Domest. Anim., 2013, vol. 48, no. 5, pp. 826–832.
Kushnareva, Y., Murphy, A.N., and Andreyev, A., Complex I-mediated reactive oxygen species generation: modulation by cytochrome c and NAD(P)+ oxidation–reduction state, Biochem. J., 2002, vol. 368, pp. 545–553.
Lasso, J.L., Noiles, E.E., Alvarez, J.G., et al., Mechanism of superoxide dismutase loss from human sperm cells during cryopreservation, J. Androl., 1994, vol. 15, no. 3, pp. 255–265.
Li, Z., Lin, Q., Liu, R., et al., Protective effects of ascorbate and catalase on human spermatozoa during cryopreservation, J. Androl., 2010, vol. 31, no. 5, pp. 437–444.
Lin, Y.C., Yao, P.L., and Richburg, J.H., FasL gene-deficient mice display a limited disruption in spermatogenesis and inhibition of mono-(2-ethylhexyl) phthalate-induced germ cell apoptosis, Toxicol. Sci., 2010, vol. 114, pp. 335–345.
Liu, Z., Zhou, S., Liao, L., et al., Jmjd1a demethylase-regulated histone modification is essential for camp-response element modulator-regulated gene expression and spermatogenesis, J. Biol. Chem., 2010, vol. 285, pp. 2758–2770.
Lu, C. and Thompson, C.B., Metabolic regulation of epigenetics, Cell Metab., 2012, vol. 16, pp. 9–17.
Maione, B., Pittoggi, C., Achene, L., et al., Activation of endogenous nucleases in mature sperm cells upon interaction with exogenous DNA, DNA Cell Biol., 1997, vol. 16, no. 9, pp. 1087–1097.
Marchetti, C., Obert, G., Deffosez, A., et al., Study of mitochondrial membrane potential, reactive oxygen species, DNA fragmentation and cell viability by flow cytometry in human sperm, Hum. Reprod., 2002, vol. 17, pp. 1257–1265.
Martí, E., Pérez‑Pé, R., Colás, C., et al., Study of apoptosis-related markers in ram spermatozoa, Anim. Reprod. Sci., 2008, vol. 106, nos. 1–2, pp. 113–132.
Martin, G., Sabido, O., Durand, P., et al., Cryopreservation induces an apoptosis-like mechanism in bull sperm, Biol. Reprod., 2004, vol. 71, pp. 28–37.
Martin, G., Cagnon, N., Sabido, O., et al., Kinetics of occurrence of some features of apoptosis during the cryopreservation process of bovine spermatozoa, Hum. Reprod., 2007, vol. 22, pp. 380–388.
Meditsinskaya khimiya i klinicheskoe primenenie dioksida kremniya (Medicinal Chemistry and Clinical Application of Silica), Chuiko, A.A., Ed., Kiev: Naukova Dumka, 2003.
Mendoza, N., Casao, A., Pérez-Pé, R., et al., New insights into the mechanisms of ram sperm protection by seminal plasma proteins, Biol. Reprod., 2013, vol. 88, no. 6, p. 149.
Miething, A., Germ-cell death during prespermatogenesis in the testis of the golden hamster, Cell Tissue Res., 1992, vol. 267, no. 3, pp. 583–590.
Muratori, M., Tamburrino, L., Marchiani, S., et al., Investigation on the origin of sperm DNA fragmentation: role of apoptosis, immaturity and oxidative stress, Mol. Med., 2015, vol. 21, pp. 109–122.
Nastasienko, N.S., Kuzema, P.O., Galagan, N.P., et al., Investigation of the biological activity of silica modified with di- and trimethylsilyl groups and sorbitol with respect to bovine sperm cells by photon correlation spectroscopy, Fizika Zhivogo, 2010, vol. 18, no. 3, pp. 99–106.
Novotny, G.W., Sonne, S.B., Nielsen, J.E., et al., Translational repression of E2F1 mRNA in carcinoma in situ and normal testis correlates with expression of the miR-17-92 cluster, Cell Death Differ., 2007, vol. 14, pp. 879–882.
Oehninger, S., Morshedi, M., Weng, S., et al., Presence and significance of somatic cell apoptosis markers in human ejaculated spermatozoa, Reprod. Biomed. Online, 2003, vol. 7, pp. 469–476.
Ortega-Ferrusola, C., Sotillo-Galan, Y., Varela-Fernandez, E., et al., Detection of “apoptosis-like” changes during the cryopreservation process in equine sperm, J. Androl., 2008, vol. 29, pp. 213–221.
Ortega-Ferrusola, C., Gonzalez Fernandez, L., Salazar Sandoval, C., et al., Inhibition of the mitochondrial permeability transition pore reduces “apoptosis like” changes during cryopreservation of stallion spermatozoa, Theriogenology, 2010, vol. 74, pp. 458–465.
Paasch, U., Grunewald, S., Fitzl, G., et al., Deterioration of plasma membrane is associated with activation of caspases in human spermatozoa, J. Androl., 2003, vol. 24, pp. 246–252.
Paasch, U., Sharma, R.K., Gupta, A.K., et al., Cryopreservation and thawing is associated with varying extent of activation of apoptotic machinery in subsets of ejaculated human spermatozoa, Biol. Reprod., 2004, vol. 71, no. 6, pp. 1828–1837.
Paoli, D., Lombardo, F., Lenzi, A., et al., Sperm cryopreservation: effects on chromatin structure, Adv. Exp. Med. Biol., 2014, vol. 791, pp. 137–150.
Pena, F.J., Johannisson, A., Wallgren, M., et al., Assessment of fresh and frozen-thawed boar semen using an annexin-V assay: a new method of evaluating sperm membrane integrity, Theriogenology, 2003, vol. 60, pp. 677–689.
Rotgers, E., Nurmio, M., Pietilä, E., et al., E2F1 controls germ cell apoptosis during the first wave of spermatogenesis, Andrology, 2015, vol. 3, no. 5, pp. 1000–1014.
Said, T.M., Gaglani, A., and Agarwal, A., Implication of apoptosis in sperm cryoinjury, Reprod. Biomed. Online, 2010, vol. 21, no. 4, pp. 456–462.
Sakkas, D., Mariethoz, E., Manicardi, G., et al., Origin of DNA damage in ejaculated human spermatozoa, Rev. Reprod., 1999a, vol. 4, pp. 31–37.
Sakkas, D., Mariethoz, E., and St. John, J.C., Abnormal sperm parameters in humans are indicative of an abortive apoptotic mechanism linked to the Fas-mediated pathway, Exp. Cell Res., 1999b, vol. 251, pp. 350–355.
Sakkas, D., Seli, E., Manicardi, G.C., et al., The presence of abnormal spermatozoa in the ejaculate: did apoptosis fail?, Hum. Fertil. (Camb.), 2004, vol. 7, pp. 99–103.
Shukla, K.K., Mahdi, A.A., and Rajender, S., Apoptosis, spermatogenesis and male infertility, Front. Biosci., 2012, vol. 4, pp. 746–754.
Stephan, H., Polzar, B., Rauch, F., et al., Distribution of deoxyribonuclease I (DNase I) and p53 in rat testis and their correlation with apoptosis, Histochem. Cell Biol., 1996, vol. 106, no. 4, pp. 383–393.
Taylor, S.L., Weng, S.L., Fox, P., et al., Somatic cell apoptosis markers and pathways in human ejaculated sperm: potential utility as indicators of sperm quality, Mol. Hum. Reprod., 2004, vol. 10, pp. 825–834.
Taylor, K., Roberts, P., Sanders, K., et al., Effect of antioxidant supplementation of cryopreservation medium on post-thaw integrity of human spermatozoa, Reprod. Biomed. Online, 2009, vol. 18, no. 2, pp. 184–189.
Thomson, L.K., Fleming, S.D., Aitken, R.J., et al., Cryopreservation-induced human sperm DNA damage is predominantly mediated by oxidative stress rather than apoptosis, Hum. Reprod., 2009, vol. 24, no. 9, pp. 2061–2070.
Tsounapi, P., Saito, M., Dimitriadis, F., et al., Antioxidant treatment with edaravone or taurine ameliorates diabetes-induced testicular dysfunction in the rat, Mol. Cell Biochem., 2012, vol. 369, pp. 195–204.
Del Valle, I., Mendoza, N., Casao, A., et al., Significance of non-conventional parameters in the evaluation of cooling-induced damage to ram spermatozoa diluted in three different media, Reprod. Domest. Anim., 2010, vol. 45, pp. e260–e268.
Varum, S., Bento, C., Sousa, A.P., et al., Characterization of human sperm populations using conventional parameters, surface ubiquitination, and apoptotic markers, Fertil. Steril., 2007, vol. 87, no. 3, pp. 572–583.
Vasicek, J., Pivko, J., and Chrenek, P., Reproductive performance of New Zealand White rabbits after depletion of apoptotic spermatozoa, Folia Biol. (Krakow), 2014, vol. 62, no. 2, pp. 109–117.
Vaux, D.L. and Korsmeyer, S.J., Cell death in development, Cell, 1999, vol. 96, pp. 245–254.
Weil, M., Jacobson, M.D., and Raff, M.C., Are caspases involved in the death of cells with a transcriptionally inactive nucleus? Sperm and chicken erythrocytes, J. Cell Sci., 1998, vol. 111, pp. 2707–2715.
Weng, S.L., Taylor, S.L., Morshedi, M., et al., Caspase activity and apoptotic markers in ejaculated human sperm, Mol. Hum. Reprod., 2002, vol. 8, no. 11, pp. 984–991.
Yamasaki, L., Jacks, T., Bronson, R., et al., Tumor induction and tissue atrophy in mice lacking E2F-1, Cell, 1996, vol. 85, pp. 537–548.
Youle, R.J. and Strasser, A., The BCL-2 protein family: opposing activities that mediate cell death, Nat. Rev. Mol. Cell Biol., 2008, vol. 9, no. 1, pp. 47–59.
Zeng, C., Tang, K., He, L., et al., Effects of glycerol on apoptotic signaling pathways during boar spermatozoa cryopreservation, Cryobiology, 2014, vol. 68, pp. 395–404.
ACKNOWLEDGMENTS
The survey was performed under the state task of the Ministry of Education of the Russian Federation according to project no. АААА-А18-118021590132-9 (registered in the Center of Information Technologies and Systems for Executive Power Authorities, Russia).
Author information
Authors and Affiliations
Corresponding authors
Additional information
Translated by O. Zhiryakova
Rights and permissions
About this article
Cite this article
Nakidkina, A.N., Kuzmina, T.I. Apoptosis in Spermatozoa and Its Role in Deteriorating Semen Quality. Russ J Dev Biol 50, 165–172 (2019). https://doi.org/10.1134/S1062360419040064
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1062360419040064