Protective effect of melatonin on alleviating early oxidative stress induced by DOX in mice spermatogenesis and sperm quality maintaining

Abstract

Doxorubicin (DOX) is an effective chemotherapy drug, but its clinical use has adverse effects on male reproduction. However, there are few studies about the specific biological processes related to male reproduction or strategies for improving fertility protection. In this paper, we examined the effects of DOX on spermatogenesis and sperm function, and tested the possible protective role of melatonin (MLT) against DOX’s reproductive toxicity. DOX-treated mice showed signs of significantly impaired spermatogenesis, including vacuolated epithelial cells, decreased testis weights, and lowered sperm counts and motility. DOX also reduced germ cell proliferation (PCNA) and meiosis-related proteins (SYCP3), but this effect could be partially improved with MLT administration. HSPA2 expression was maintained, which indicated that although MLT did not improve sperm motility, it did have a significant protective effect on elongated sperm. IVF results showed that MLT could partially promote two-cell and blastocyte development that was restricted by DOX. MLT reversed DOX-driven changes in the testes, including the antioxidant indices of SOD1, CAT and PRDX6, and the apoptotic indices of BAX and Caspase3. These results suggest that MLT effectively prevents DOX-induced early reproductive toxicity, and increase our understanding of the molecular mechanisms underlying DOX’s effects on male reproduction and the protective mechanism of MLT.

Protective effects of exogenous melatonin therapy against oxidative stress to male reproductive tissue caused by anti-cancer chemical and radiation therapy: a systematic review and meta-analysis of animal studies

“…The studies were published from Iran (n=11) ( 20 , 40 , 45 , 53 – 55 , 59 , 61 , 65 , 67 , 68 ), Turkey (n=9) ( 21 , 31 , 36 – 39 , 43 , 47 , 64 ), Egypt (n=9) ( 33 – 35 , 41 , 42 , 44 , 46 , 48 , 60 ), China (n=7) ( 14 , 19 , 32 , 49 , 62 , 63 , 66 ), India (n=4) ( 22 , 50 , 52 , 57 ), Thailand (n=1) ( 58 ), Nigeria (n=1) ( 56 ), and South Korea (n=1) ( 51 ). Studies employed rats (n=25) ( 20 – 22 , 31 , 34 – 37 , 39 , 41 – 44 , 46 – 48 , 51 , 56 – 58 , 61 , 62 , 64 , 65 , 68 ) and mice (n=18) ( 14 , 19 , 32 , 33 , 38 , 40 , 45 , 49 , 50 , 52 – 55 , 59 ,…”

Protective effects of melatonin against physical injuries to testicular tissue: A systematic review and meta-analysis of animal models

“…Melatonin protects the reproductive system against the toxicity of chemotherapeutic agents (87). Zi et al reported the favorable effects of melatonin on doxorubicin-induced impaired spermatogenesis and sperm quality, except for sperm motility (88). Melatonin also suppressed bleomycin, etoposide, and cisplatin-induced testicular damage by ameliorating histopathological alterations of testes, testicular weight, and sperm motility, viability, and morphology, but not sperm count and its progressive motility (89).…”

Melatonin improves the ability of spermatozoa to bind with oocytes in the mouse

“…Mice in the control group received an intraperitoneal injection of 100 μL normal saline (0.9% NaCl with 0.5% ethanol) daily for 35 days, while mice in the melatonin-treated group received an intraperitoneal injection of melatonin (10 mg/kg body weight, dissolved in 0.9% NaCl + 0.5% ethanol) daily for 35 days. The dosage and duration of melatonin treatment referred to our previous report (Wang et al 2022a;Zi et al 2022), and the administration of melatonin was performed at 9 am every day. On the 35th day, all mice were killed (1.25% 2,2,2-tribromoethanol sterile anesthetic, 0.2mL/kg, intraperitoneal injection), one of the testes and epididymides of each mouse were collected for fixation in Bouin's solution (HT10132, Sigma, St. Louis, MO, USA) for immunochemistry staining and microscopic evaluation, and the other testis and epididymis were collected for sperm preparation and mRNA and protein extraction.…”

“…For full list of author affiliations and declarations see end of paper Melatonin is synthesised not only by the pineal gland, but also by reproductive organs (Huai et al 2012). It is also thought to play an important role in reproductive development and regulation (Zi et al 2022). Due to living habits, work pressure, environmental pollution and other factors, more and more men have sub-health status, and the age of marriage and child bearing is getting older (Whiteford et al 2013).…”

“…Melatonin could ameliorate reproductive dysfunctions in males associated with pathological conditions and toxicant exposure (Rocha et al 2015). Melatonin also has been used to regulate sleep cycles and the other systemic diseases, and it also serves as a promising antioxidant for improving male sub-fertility (Tordjman et al 2017;Zi et al 2022). As a commonly used antioxidant, the effects of melatonin in reproductively normal males have received less attention.…”