A.A. Kamalov −
Dr. Sc. (Med.), Professor, Academician RAS, Director, Medical Research and Education Center
of Lomonosov Moscow State University; Head of Department of Urology and Andrology,
Faculty of Fundamental Medicine, Lomonosov Moscow State University
E-mail: armais.kamalov@rambler.ru
D.A. Ohobotov −
Ph.D. (Med.), Urologist, Medical Research and Education Center of Lomonosov Moscow State University;
Associate Professor, Department of Andrology and Urology, Faculty of Fundamental Medicine,
Lomonosov Moscow State University
E-mail: 14072003@rambler.ru
A.Yu. Efimenko −
Ph. D. (Med.), Senior Research Scientist, Institute for Regenerative Medicine,
Medical Research and Education Center of Lomonosov Moscow State University
E-mail: efimenkoan@gmail.com
G.D. Sagaradze −
Laboratory Assistant, Institute for Regenerative Medicine, Lomonosov Moscow State University
E-mail: georgysagaradze@gmail.com
M.E. Chaliy –
Dr.Sc. (Med.), Professor, Leading Research Scientist, Medical Research and Education Center
of Lomonosov Moscow State University;
E-mail: chalyy@bk.ru
A.N. Nizov –
Urologist, Junior Research Scientist, Moscow Research and Education Center
of Lomonosov Moscow State University,
E-mail: nizovale@gmail.com
V.K. Dzitiev –
Ph.D. (Med.), Head of Urological Service, Medical Research and Education Center
of Lomonosov Moscow State University
E-mail: vitdok@mail.ru
E.V. Afanasyevskaya –
Resident Physician, Department of Urology and Andrology, Faculty of Fundamental Medicine,
Lomonosov Moscow State University
E-mail: e.afanasyevskaya@mail.ru
A.A. Strigunov –
Resident Physician, Department of Urology and Andrology, Faculty of Fundamental Medicine,
Lomonosov Moscow State University
E-mail: an-strigunov@yandex.ru
O.Y. Nesterova –
Student, Faculty of Fundamental Medicine, Lomonosov Moscow State University
E-mail: oy.nesterova@gmail.com

Spermatogenesis is a process of division and differentiation of sperm, which includes three stages: spermatocytogenesis, meiosis and spermatogenesis. At the first stage there is a mitotic division of stem cells with the formation of primary spermatocytes. Meiosis leads to the formation of four haploid spermatids. Spermatogenesis consists in the differentiation of spherical sperm into mature cells in the absence of their division.

The most severe damage during spermatogenesis is observed at the stage of spermatocytogenesis. In addition to the effects of endogenous hormones, the spermatogenic epithelium is daily exposed to a number of exogenous factors. Male sex cells are extremely sensitive to elevated temperatures, malnutrition, androgenic drugs, toxic effects of metals, x-rays, dioxins, alcohol, infectious agents and other factors. These factors can cause a temporary or permanent response, characterized by a decrease in the total number of germ cells, both in absolute values and relative to Sertoli cells, as well as the formation of multinuclear giant layers.

With the development of pharmacotherapy, it became clear that many drugs, in addition to their main therapeutic action, can affect other organs, including the testes, providing spermatotoxic effect on the main stages of spermatogenesis. In addition to drugs, other substances contained in exhaust gases, tobacco smoke, water and even food have a negative impact on the development and differentiation of sperm. Due to the presence of such a variety of exogenous effects, we have analyzed the available literature data with a review of experimental models for the study of spermatotoxic action of drugs in order to develop a biological model of controlled toxic damage of spermatogenesis.

It was found that the most persistent and irreversible disorders occur against the background of taking anticancer drugs, busulfan, cytostatics, heavy metal salts, mycotoxins and polycyclic aromatic hydrocarbons. The other classes of pharmacotherapeutic agents cause temporary disorders that can be compensated after discontinuation of these drugs.

To assess the proposed protective mechanisms of action of new drugs for the recovery of spermatogenesis in toxic damage, it is most appropriate to use busulfan, cytostatic and heavy metal salt damage models, as the mechanisms of the damaging effects of these drugs are well described in the literature, the models are repeatable and allow to obtain a clear histomorphological picture.

1. Nishimura H., L’Hernault S.W. Spermatogenesis // Curr. Biol. England. 2017. V. 27. № 18. P. R988–R994.
2. Smith C.G. Drug effects on male sexual function // Clin. Obstet. Gynecol. United States. 1982. V. 25. № 3. P. 525–531.
3. Zhang X., Yamamoto N., Soramoto S., Takenaka I. Cisplatin-induced germ cell apoptosis in mouse testes // Arch. Androl. England. 2001. V. 46. № 1. P. 43–49.
4. Xie R., Chen L., Wu H., Chen T., Wang F., Chen X., Sun H., Li X. GnRH Antagonist Improves Pubertal Cyclophosphamide-Induced Long-Term Testicular Injury in Adult Rats // Int. J. Endocrinol. Egypt. 2018. V. 2018. P. 4272575.
5. Foresta C., Garolla A., Cosci I., Menegazzo M., Ferigo M., Gandin V., De Toni L. Role of zinc trafficking in male fertility: from germ to sperm // Hum. Reprod. England. 2014. V. 29. № 6. P. 1134–1145.
6. Cao Y., Wang X., Li S., Wang H., Yu L., Wang P. The Effects of l-Carnitine Against Cyclophosphamide-Induced Injuries in Mouse Testis // Basic Clin. Pharmacol. Toxicol. England. 2017. V. 120. № 2. P. 152–158.
7. Turgut G., Abban G., Turgut S., Take G. Effect of overdose zinc on mouse testis and its relation with sperm count and motility // Biol. Trace Elem. Res. United States. 2003. V. 96. № 1–3. P. 271–279.
8. Rivkees S.A., Crawford J.D. The relationship of gonadal activity and chemotherapy-induced gonadal damage // JAMA. United States. 1988.
   V. 259. № 14. P. 2123–2125.
9. Qu N., Kuramasu M., Hirayanagi Y., Nagahori K., Hayashi S., Ogawa Y., Terayama H., Suyama K., Naito M., Sakabe K., Itoh M. Gosha-Jinki-Gan Recovers Spermatogenesis in Mice with Busulfan-Induced Aspermatogenesis // Int. J. Mol. Sci. Switzerland. 2018. V. 19. № 9. P. 2606.
10. Skurikhin E.G., Pakhomova A.V., Pershina O.V., Ermolaeva L.A., Ermakova N.N., Krupin V.A., Pan E.S., Kudryashova A.I., Rybalkina O.Y., Zhdanov V.V., Goldberg V.E., Dygai A.M. Regenerative Potential of Stem and Progenitor Cells from Ischemic Testes of C57Bl/6 Mice in Culture and in the Model of Spermatogenesis Suppression Caused by Busulfan // Bull. Exp. Biol. Med. United States. 2017. V. 162. № 3. P. 400–405.
11. Panahi M., Keshavarz S., Rahmanifar F., Tamadon A., Mehrabani D., Karimaghai N., Sepehrimanesh M., Aqababa H. Busulfan induced azoospermia: Stereological evaluation of testes in rat // Vet. Res. forum an Int. Q. J. Iran. 2015. V. 6. № 4. P. 273–278.
12. Fang F., Ni K., Cai Y., Zhao Q., Shang J., Zhang X., Shen S., Xiong C. Busulfan administration produces toxic effects on epididymal morphology and inhibits the expression of ZO-1 and vimentin in the mouse epididymis // Biosci. Rep. England. 2017. V. 37. № 6. P. BSR20171059.
13. Cyr D.G., Gregory M., Dube E., Dufresne J., Chan P.T.K., Hermo L. Orchestration of occludins, claudins, catenins and cadherins as players involved in maintenance of the blood-epididymal barrier in animals and humans // Asian J. Androl. China. 2007. V. 9. № 4. P. 463–475.
14. Ramesh A., Walker S.A., Hood D.B., Guillen M.D., Schneider K., Weyand E.H. Bioavailability and risk assessment of orally ingested polycyclic aromatic hydrocarbons // Int. J. Toxicol. United States. 2004. V. 23. № 5. P. 301–333.
15. Perera F.P., Santella R.M., Brenner D., Young T.L., Weinstein I.B. Application of biological markers to the study of lung cancer causation and prevention // IARC Sci. Publ. France. 1988. № 89. P. 451–459.
16. Chao M.-R., Wang C.-J., Wu M.-T., Pan C.-H., Kuo C.-Y., Yang H.-J., Chang L.W., Hu C.-W. Repeated measurements of urinary methylated/oxidative DNA lesions, acute toxicity, and mutagenicity in coke oven workers // Cancer Epidemiol. Biomarkers Prev. United States. 2008.
    V. 17. № 12. P. 3381–3389.
17. Liu A.-L., Lu W.-Q., Wang Z.-Z., Chen W.-H., Lu W.-H., Yuan J., Nan P.-H., Sun J.-Y., Zou Y.-L., Zhou L.-H., Zhang C., Wu T.-C. Elevated levels of urinary 8-hydroxy-2 -deoxyguanosine, lymphocytic micronuclei, and serum glutathione S-transferase in workers exposed to coke oven emissions // Environ. Health Perspect. United States. 2006. V. 114. № 5. P. 673–677.
18. Park J.-H., Troxel A.B., Harvey R.G., Penning T.M. Polycyclic aromatic hydrocarbon (PAH) o-quinones produced by the aldo-keto-reductases (AKRs) generate abasic sites, oxidized pyrimidines, and 8-oxo-dGuo via reactive oxygen species // Chem. Res. Toxicol. United States. 2006.
    V. 19. № 5. P. 719–728.
19. Hsu P.-C., Chen I.-Y., Pan C.-H., Wu K.-Y., Pan M.-H., Chen J.-R., Chen C.-J., Chang-Chien G.-P., Hsu C.-H., Liu C.-S., Wu M.-T. Sperm DNA damage correlates with polycyclic aromatic hydrocarbons biomarker in coke-oven workers // Int. Arch. Occup. Environ. Health. Germany. 2006. V. 79. № 5. P. 349–356.
20. Xia Y., Han Y., Zhu P., Wang S., Gu A., Wang L., Lu C., Fu G., Song L., Wang X. Relation between urinary metabolites of polycyclic aromatic hydrocarbons and human semen quality // Environ. Sci. Technol. United States. 2009. V. 43. № 12. P. 4567–4573.
21. Godschalk R.W., Ostertag J.U., Zandsteeg A.M., Van Agen B., Neuman H.A., Van Straaten H., Van Schooten F.J. Impact of GSTM1 on aromatic-DNA adducts and p53 accumulation in human skin and lymphocytes // Pharmacogenetics. England. 2001. V. 11. № 6. P. 537–543.
22. Selevan S.G., Borkovec L., Slott V.L., Zudova Z., Rubes J., Evenson D.P., Perreault S.D. Semen quality and reproductive health of young Czech men exposed to seasonal air pollution // Environ. Health Perspect. United States. 2000. V. 108. № 9. P. 887–894.
23. Richburg J.H., Boekelheide K. Mono-(2-ethylhexyl) phthalate rapidly alters both Sertoli cell vimentin filaments and germ cell apoptosis in young rat testes // Toxicol. Appl. Pharmacol. United States. 1996. V. 137. № 1. P. 42–50.
24. Zhang L., Gao M., Zhang T., Chong T., Wang Z., Zhai X., Wu Z., Li H. Protective Effects of Genistein against Mono-(2-ethylhexyl) Phthalate-Induced Oxidative Damage in Prepubertal Sertoli Cells // Biomed Res. Int. United States. 2017. V. 2017. P. 2032697.
25. Ramesh A., Inyang F., Hood D.B., Archibong A.E., Knuckles M.E., Nyanda A.M. Metabolism, bioavailability, and toxicokinetics of benzo(alpha)pyrene in F-344 rats following oral administration // Exp. Toxicol. Pathol. Germany. 2001. V. 53. № 4. P. 275–290.
26. Georgellis A., Toppari J., Veromaa T., Rydstrom J., Parvinen M. Inhibition of meiotic divisions of rat spermatocytes in vitro by polycyclic aromatic hydrocarbons // Mutat. Res. Netherlands. 1990. V. 231. № 2. P. 125–135.
27. Gaspari L., Chang S.S., Santella R.M., Garte S., Pedotti P., Taioli E. Polycyclic aromatic hydrocarbon-DNA adducts in human sperm as a marker of DNA damage and infertility // Mutat. Res. Netherlands. 2003. V. 535. № 2. P. 155–160.
28. Leduc F., Nkoma G.B., Boissonneault G. Spermiogenesis and DNA repair: a possible etiology of human infertility and genetic disorders // Syst. Biol. Reprod. Med. England. 2008. V. 54. № 1. P. 3–10.
29. Grollman A.P., Moriya M. Mutagenesis by 8-oxoguanine: an enemy within // Trends Genet. England. 1993. V. 9. № 7. P. 246–249.
30. Abouzied M.M., Azcona J.I., Braselton W.E., Pestka J.J. Immunochemical assessment of mycotoxins in 1989 grain foods: evidence for deoxynivalenol (vomitoxin) contamination // Appl. Environ. Microbiol. United States. 1991. V. 57. № 3. P. 672–677.
31. Logrieco A., Moretti A., Castella G., Kostecki M., Golinski P., Ritieni A., Chelkowski J. Beauvericin production by Fusarium species // Appl. Environ. Microbiol. United States. 1998. V. 64. № 8. P. 3084–3088.
32. Shubina O.S., Dudenkova N.A. The effect of lead on the process of spermatogenesis in sex glands of male albino rats // Vet. world. India. 2016. V. 9. № 10. P. 1129–1134.
33. Aver'yanova A.Yu., Surikova N.E., Bakanovich I.B., Koval' K.G. Sudebno-medicinskoe znachenie lekarstvennyh preparatov, ugnetayushchih spermatogenez // Materialy VI Vserossijskogo s"ezda sudebnyh medikov. M.: Izdat. centr «Akademiya». 2005. S. 21.
34. Kushniruk Yu.I. Vliyanie nekotoryh antibiotikov na spermatogenez // Problemy seksopatologii i besplodiya: Materialy II respublikanskoj konferencii seksopatologov. Voroshilovgrad. 1972; Kiev. 1973. S. 209–214.
35. Lisakovskaya O.V. Vliyanie antibakterial'nyh preparatov na kachestvo eyakulyata muzhchin reproduktivnogo vozrasta // Tihookeanskij medicinskij zhurnal. 2003. № 3. S. 26–27.
36. Arabidze G.G. Arterial'naya gipertenziya: primenenie ingibitorov angiotenzinprevrashchayushchego fermenta // RMZh. 1999. № 15. S. 702–706.
37. Grimm R.H.J., Grandits G.A., Prineas R.J., McDonald R.H., Lewis C.E., Flack J.M., Yunis C., Svendsen K., Liebson P.R., Elmer P.J. Long-term effects on sexual function of five antihypertensive drugs and nutritional hygienic treatment in hypertensive men and women. Treatment of Mild Hypertension Study (TOMHS) // Hypertens. (Dallas, Tex. 1979). United States. 1997. V. 29. № 1. Pt. 1. P. 8–14.
38. Breikaa R.M., Mosli H.A., Abdel-Naim A.B. Influence of Onabotulinumtoxin A on testes of the growing rat // J. Biochem. Mol. Toxicol. 2016. V. 30. № 12. P. 608–613.
39. Miura T., Miura C., Konda Y., Yamauchi K. Spermatogenesis-preventing substance in Japanese eel. // Development. England. 2002. V. 129.
    № 11. P. 2689–2697.
40. Miura C., Kuwahara R., Miura T. Transfer of spermatogenesis-related cDNAs into eel testis germ-somatic cell coculture pellets by electroporation: methods for analysis of gene function // Mol. Reprod. Dev. United States. 2007. V. 74. № 4. P. 420–427.
41. Mouyis M., Flint J.D., Giles I.P. Safety of anti-rheumatic drugs in men trying to conceive: A systematic review and analysis of published evidence // Semin. Arthritis Rheum. United States. 2019. V. 48. № 5. P. 911–920.
42. Feagins L.A., Kane S.V. Sexual and reproductive issues for men with inflammatory bowel disease // Am. J. Gastroenterol. United States. 2009.
    V. 104. № 3. P. 768–773.
43. Fukushima T., Kato M., Adachi T., Hamada Y., Horimoto M., Komiyama M., Mori C., Horii I. Effects of sulfasalazine on sperm acrosome reaction and gene expression in the male reproductive organs of rats // Toxicol. Sci. United States. 2005. V. 85. № 1. P. 675–682.
44. Freeman J.G., Reece V.A., Venables C.W. Sulphasalazine and spermatogenesis // Digestion. Switzerland. 1982. V. 23. № 1. P. 68–71.
45. O’Morain C., Smethurst P., Dore C.J., Levi A.J. Reversible male infertility due to sulphasalazine: studies in man and rat // Gut. England. 1984.
    V. 25. № 10. P. 1078–1084.
46. Toovey S., Hudson E., Hendry W.F., Levi A.J. Sulphasalazine and male infertility: reversibility and possible mechanism // Gut. England. 1981.
    V. 22. № 6. P. 445–451.
47. Shin T., Okada H. Infertility in men with inflammatory bowel disease // World J. Gastrointest. Pharmacol. Ther. United States. 2016. V. 7. № 3. P. 361–369.
48. Stevison F., Jing J., Tripathy S., Isoherranen N. Role of Retinoic Acid-Metabolizing Cytochrome P450s, CYP26, in Inflammation and Cancer // Adv. Pharmacol. United States. 2015. V. 74. P. 373–412.
49. Hong N., Li M., He B., Hong Y. Biological Systems : Open Access Retinoic Acid Regulates Germ Gene Transcription In Vitro and Spermatogenesis in Testicular // Organ Culture. 2012. V. 1. № 1. P. 1–7.
50. Chung S.S.W., Wang X., Wolgemuth D.J. Prolonged Oral Administration of a Pan-Retinoic Acid Receptor Antagonist Inhibits Spermatogenesis in Mice With a Rapid Recovery and Changes in the Expression of Influx and Efflux Transporters // Endocrinology. United States. 2016. V. 157. № 4. P. 1601–1612.
51. Yoo Y.J., Kim H., Park S.R., Yoon Y.J. An overview of rapamycin: from discovery to future perspectives // J. Ind. Microbiol. Biotechnol. Germany. 2017. V. 44. № 4–5. P. 537–553.
52. Fan Y.L., Hou H.W., Tay H.M., Guo W.M., Berggren P.-O., Loo S.C.J. Preservation of Anticancer and Immunosuppressive Properties of Rapamycin Achieved Through Controlled Releasing Particles // AAPS PharmSciTech. United States. 2017. V. 18. № 7. P. 2648–2657.
53. Boobes Y., Bernieh B., Saadi H., Raafat Al Hakim M., Abouchacra S. Gonadal dysfunction and infertility in kidney transplant patients receiving sirolimus // Int. Urol. Nephrol. Netherlands. 2010. V. 42. № 2. P. 493–498.
54. Deutsch M.A., Kaczmarek I., Huber S., Schmauss D., Beiras-Fernandez A., Schmoeckel M., Ochsenkuehn R., Meiser B., Mueller-Hoecker J., Reichart B. Sirolimus-associated infertility: case report and literature review of possible mechanisms // Am. J. Transplant. United States. 2007.
    V. 7. № 10. P. 2414–2421.
55. Mukherjee A., Koli S., Reddy K.V.R. Rapamycin (Sirolimus) alters mechanistic target of rapamycin pathway regulation and microRNA expression in mouse meiotic spermatocytes // Andrology. England. 2015. V. 3. № 5. P. 979–990.
56. Kaczmarek I., Groetzner J., Adamidis I., Landwehr P., Mueller M., Vogeser M., Gerstorfer M., Uberfuhr P., Meiser B., Reichart B. Sirolimus impairs gonadal function in heart transplant recipients // Am. J. Transplant. United States. 2004. V. 4. № 7. P. 1084–1088.
57. Verhoeven G., Willems A., Denolet E., Swinnen J. V, De Gendt K. Androgens and spermatogenesis: lessons from transgenic mouse models // Philos. Trans. R. Soc. Lond. B. Biol. Sci. England. 2010. V. 365. № 1546. P. 1537–1556.
58. de Souza G.L., Hallak J. Anabolic steroids and male infertility: a comprehensive review // BJU Int. England. 2011. V. 108. № 11. P. 1860–1865.
59. Avant R.A., Charchenko C.M., Alom M., Westerman M.E., Maldonado F., Miest T., Trost L. Medication patterns and fertility rates in a cohort of anabolic steroid users // Transl. Androl. Urol. China. 2018. V. 7. № Suppl 2. P. S198–S204.
60. McBride J.A., Coward R.M. Recovery of spermatogenesis following testosterone replacement therapy or anabolic-androgenic steroid use // Asian J. Androl. China. 2016. V. 18. № 3. P. 373–380.
61. Constantin S. Progress and Challenges in the Search for the Mechanisms of Pulsatile Gonadotropin-Releasing Hormone Secretion // Front. Endocrinol. (Lausanne). Switzerland. 2017. V. 8. P. 180.
62. Rapoport L.M., Demidko Yu.L. Primenenie Buserelina-depo – agonista gonadotropin-rilizing-gormonov v lechenii raka prostaty // Andrologiya i genital'naya hirurgiya. 2014. № 3. S. 74–79.
63. Avakyan G.N., Badalyan O.L., Krikova E.V., Chukanova A.S., Burd S.G. Reproduktivnye narusheniya u muzhchin s epilepsiej // Epilepsiya i paroksizmal'nye sostoyaniya. 2010. V. 2. № 1. S. 30–36.
64. Bauer J., Klingmuller D. [Which antiepileptic drug for men with epilepsy? A critical epileptological and andrological review] // Nervenarzt. Germany. 2008. V. 79. № 12. P. 1407–1412, 1414–1415.
65. Morrell M.J., Montouris G.D. Reproductive disturbances in patients with epilepsy // Cleve. Clin. J. Med. United States. 2004. V. 71. Suppl 2.
    P. S19–24.
66. Sukhorum W., Iamsaard S. Changes in testicular function proteins and sperm acrosome status in rats treated with valproic acid // Reprod. Fertil. Dev. Australia. 2017. V. 29. № 8. P. 1585–1592.
67. Song B.-J., Moon K.-H., Upreti V. V, Eddington N.D., Lee I.J. Mechanisms of MDMA (ecstasy)-induced oxidative stress, mitochondrial dysfunction, and organ damage // Curr. Pharm. Biotechnol. Netherlands. 2010. V. 11. № 5. P. 434–443.
68. Sasikumar S., Dakshayani D., Sarasa D. An investigation of DNA fragmentation and morphological changes caused by bacteria and fungi in human spermatozoa // Int. J. Curr. Microbiol. App. Sci. India. 2013. V. 2. № 4. P. 84–96.
69. Khin N.A., Kronstein P.D., Yang P., Ishida E., Hung H.M.J., Mathis M. V, Unger E.F., Temple R.J. Regulatory and scientific issues in studies to evaluate sexual dysfunction in antidepressant drug trials // J. Clin. Psychiatry. United States. 2015. V. 76. № 8. P. 1060–1063.
70. Pourmasumi S., Sabeti P., Rahiminia T., Mangoli E., Tabibnejad N., Talebi A.R. The etiologies of DNA abnormalities in male infertility: An assessment and review // Int. J. Reprod. Biomed. (Yazd, Iran). Iran. 2017. V. 15. № 6. P. 331–344.
71. Tanrikut C., Feldman A.S., Altemus M., Paduch D.A., Schlegel P.N. Adverse effect of paroxetine on sperm // Fertil. Steril. United States. 2010.
    V. 94. № 3. P. 1021–1026.
72. Tanrikut C., Schlegel P.N. Antidepressant-associated changes in semen parameters // Urology. United States. 2007. V. 69. № 1. P. 185.e5–7.
73. Hanssens L., L’Italien G., Loze J.-Y., Marcus R.N., Pans M., Kerselaers W. The effect of antipsychotic medication on sexual function and serum prolactin levels in community-treated schizophrenic patients: results from the Schizophrenia Trial of Aripiprazole (STAR) study (NCT00237913) // BMC Psychiatry. England. 2008. V. 8. P. 95.
74. Dabbous Z., Atkin S.L. Hyperprolactinaemia in male infertility: Clinical case scenarios // Arab. J. Urol. United States. 2018. V. 16. № 1. P. 44–52.
75. Wieck A., Haddad P. Hyperprolactinaemia caused by antipsychotic drugs // BMJ (Clinical research ed.). England. 2002. V. 324. № 7332. P. 250–252.
76. Whirledge S., Cidlowski J.A. A role for glucocorticoids in stress-impaired reproduction: beyond the hypothalamus and pituitary // Endocrinology. United States. 2013. V. 154. № 12. P. 4450–4468.
77. Breen K.M., Thackray V.G., Hsu T., Mak-McCully R.A., Coss D., Mellon P.L. Stress levels of glucocorticoids inhibit LHbeta-subunit gene expression in gonadotrope cells // Mol. Endocrinol. United States. 2012. V. 26. № 10. P. 1716–1731.
78. Whirledge S., Cidlowski J.A. Glucocorticoids, stress, and fertility // Minerva Endocrinol. Italy. 2010. V. 35. № 2. P. 109–125.
79. Morais R.D.V.S., Nobrega R.H., Gomez-Gonzalez N.E., Schmidt R., Bogerd J., Franca L.R., Schulz R.W. Thyroid hormone stimulates the proliferation of Sertoli cells and single type A spermatogonia in adult zebrafish (Danio rerio) testis // Endocrinology. United States. 2013. V. 154. № 11. P. 4365–4376.
80. Laszczynska M., Sluczanowska-Glabowska S., Piasecka M., Skowron J., Debinska-Szymanska T. Germ cells with nuclear DNA fragmentation related to apoptotic cells in rat testis in experimental hyperprolactinemia induced by metoclopramide // Folia Histochem. Cytobiol. Poland. 2002.
    V. 40. № 2. P. 163–164.
81. Hori J.-I., Koga D., Kakizaki H., Watanabe T. Differential effects of depot formulations of GnRH agonist leuprorelin and antagonist degarelix on the seminiferous epithelium of the rat testis // Biomed. Res. Japan. 2018. V. 39. № 4. P. 197–214.
82. Amory J.K., Wang C., Swerdloff R.S., Anawalt B.D., Matsumoto A.M., Bremner W.J., Walker S.E., Haberer L.J., Clark R.V. The effect of 5alpha-reductase inhibition with dutasteride and finasteride on semen parameters and serum hormones in healthy men // J. Clin. Endocrinol. Metab. United States. 2007. V. 92. № 5. P. 1659–1665.
83. Nusier M.K., Bataineh H.N., Daradka H.M. Adverse effects of propranolol on reproductive function in adult male mice // Pakistan J. Biol. Sci. PJBS. Pakistan. 2007. V. 10. № 16. P. 2728–2731.
84. Kjaergaard N., Kjaergaard B., Lauritsen J.G. Prazosin, an adrenergic blocking agent inadequate as male contraceptive pill // Contraception. United States. 1988. V. 37. № 6. P. 621–629.
85. Hibi H., Yamamoto M., Miyake K. Effect of alpha-blockers on epididymal sperm concentration, motility and testicular productivity in the rat // Hinyokika Kiyo. Japan. 1996. V. 42. № 5. P. 357–360.
86. Millsop J.W., Heller M.M., Eliason M.J., Murase J.E. Dermatological medication effects on male fertility // Dermatol. Ther. United States. 2013.
    V. 26. № 4. P. 337–346.
87. Shin J.-H., Moon H.J., Kang I.H., Kim T.S., Kim I.Y., Park I.S., Kim H.S., Jeung E.B., Han S.-Y. Repeated 28-day oral toxicity study of ketoconazole in rats based on the draft protocol for the “Enhanced OECD Test Guideline No. 407” to detect endocrine effects // Arch. Toxicol. Germany. 2006. V. 80. № 12. P. 797–803.
88. Shayakhmetova G.M., Bondarenko L.B., Voronina A.K., Matvienko A. V, Kitam V., Kovalenko V.M. Repeated administration of ethambutol in therapeutic dose causes testes alteration and spermatogenesis disruption in Wistar rats // Hum. Exp. Toxicol. England. 2017. V. 36. № 5. P. 520–533.
89. Shayakhmetova G.M., Bondarenko L.B., Voronina A.K., Anisimova S.I., Matvienko A.V., Kovalenko V.M. Induction of CYP2E1 in testes of isoniazid-treated rats as possible cause of testicular disorders // Toxicol. Lett. Netherlands. 2015. V. 234. № 2. P. 59–66.
90. Bondarenko L.B., Shayakhmetova G.M., Byshovets T.F., Kovalenko V.M. Pyrazinamide-mediated changes in rat type I collagen and spermatogenesis indices // Acta Pol. Pharm. Poland. 2011. V. 68. № 2. P. 285–290.
91. Kul’chavenia E.V., Brizhitiuk E.V., Medvedev S.A. [Toxic effect of antituberculous drugs on spermatogenesis] // Probl. Tuberk. Russia (Federation). 2002. № 5. P. 29–32.
92. Pons-Rejraji H., Brugnon F., Sion B., Maqdasy S., Gouby G., Pereira B., Marceau G., Gremeau A.-S., Drevet J., Grizard G., Janny L., Tauveron I. Evaluation of atorvastatin efficacy and toxicity on spermatozoa, accessory glands and gonadal hormones of healthy men: a pilot prospective clinical trial // Reprod. Biol. Endocrinol. England. 2014. V. 12. P. 65.
93. Leite G.A.A., Rosa J. de L., Sanabria M., Cavariani M.M., Franci J.A.A., Pinheiro P.F.F., Kempinas W.D.G. Delayed reproductive development in pubertal male rats exposed to the hypolipemiant agent rosuvastatin since prepuberty // Reprod. Toxicol. United States. 2014. V. 44. P. 93–103.
94. Nna V.U., Udefa A.L., Ofutet E.O., Osim E.O. Testicular and Epididymal Histology of Rats Chronically Administered High Doses of Phosphodiesterase-5 Inhibitors and Tramadol // Niger. J. Physiol. Sci. Nigeria. 2017. V. 32. № 1. P. 55–61.
95. Salian S., Doshi T., Vanage G. Perinatal exposure of rats to Bisphenol A affects fertility of male offspring-an overview // Reprod. Toxicol. United States. 2011. V. 31. № 3. P. 359–362.
96. Tarapore P., Hennessy M., Song D., Ying J., Ouyang B., Govindarajah V., Leung Y.-K., Ho S.-M. High butter-fat diet and bisphenol A additively impair male rat spermatogenesis // Reprod. Toxicol. United States. 2017. V. 68. P. 191–199.
97. Ho S.-M., Cheong A., Lam H.-M., Hu W.-Y., Shi G.-B., Zhu X., Chen J., Zhang X., Medvedovic M., Leung Y.-K., Prins G.S. Exposure of Human Prostaspheres to Bisphenol A Epigenetically Regulates SNORD Family Noncoding RNAs via Histone Modification // Endocrinology. United States. 2015. V. 156. № 11. P. 3984–3995.
98. Heudorf U., Mersch-Sundermann V., Angerer J. Phthalates: toxicology and exposure // Int. J. Hyg. Environ. Health. Germany. 2007. V. 210.
    № 5. P. 623–634.
99. Moustafa G.G., Ahmed A.A.M. Impact of prenatal and postnatal exposure to bisphenol A on female rats in a two generational study: Genotoxic and immunohistochemical implications // Toxicol. reports. Ireland. 2016. V. 3. P. 685–695.