The effects of melatonin on oxidative stress and prevention of primordial follicle loss via activation of mTOR pathway in the rat ovary

Abstract

Mammalian Target of Rapamycin (mTOR) signaling pathway has important roles in the regulation of puberty onset, gonadotropin secretion, follicular development and ovulation. Melatonin (N-acetyl-5-methoxytryptamine) is a lipophilic hormone has multiple functions in regulating the fertility. Recent studies have shown that melatonin affected the number or maturation of follicles in the ovary. The aim of this study was to investigate the effects of melatonin on mTOR expression and quantity of follicle in rat ovary. In the present study, a total of 45 female rats were randomly divided into three groups. Group 1; Control (C), Group 2: Vehicle (V) and Group 3; Melatonin (M). Melatonin was administered intraperitoneally at a dose of 50 mg/kg/day for 30 days in Melatonin group. The effects of Melatonin on the expression of mTOR and downstream components were determined by Western Blot and Reverse Transcriptase PCR analysis. Upon Western Blot and RT-PCR evaluations, we detected higher expression and activation of mTOR, P70S6K, PKCalpha, PCNA and higher numbers of primordial follicles in melatonin group compared with V and C group. In addition to this results, melatonin decreased oxidative stress markers, such as MDA, on the contrary, levels of antioxidative markers, such as CAT and GPx, were increased by melatonin in rat ovary. This study indicated that melatonin may have a significant protective effect on primordial follicles and increase the expression of mTOR and downstream components in rat ovary. Melatonin treatment may have a beneficial effect on fertility.

Identification of oxidative stress–related Xdh gene as a di(2‐ethylhexyl)phthalate (DEHP) target and the use of melatonin to alleviate the DEHP‐induced impairments in newborn mouse ovaries

“…Several researches demonstrated that melatonin can alleviate the decline of oocyte quality in mice induced by bisphenol A (BPA) and prevent premature ovarian failure during chemotherapy and the loss of dormant primordial follicles caused by cisplatin . Furthermore, melatonin may also protect primitive follicles by increasing the expression of components downstream of mTOR in adult rat ovaries …”

“…29 Furthermore, melatonin may also protect primitive follicles by increasing the expression of components downstream of mTOR in adult rat ovaries. 30 For these reasons, the present study re-examines the negative effects of DEHP on germ cell cyst breakdown and primordial follicle assembly in newborn mouse ovaries. To do so, we performed a transcriptome analysis which revealed downregulation of the oxidative stress-related gene Xdh (Xanthine dehydrogenase) as one of the major targets of DEHP.…”

Melatonin Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibiting Autophagy Via an AMPK/mTOR Signaling Pathway

“…A study by Behram et al showed that melatonin may have a significant protective effect on primordial follicles via activation of the mTOR pathway [25]. The findings of Kang, et al suggest that melatonin downregulates autophagy via activation of mTOR signaling which may in turn contribute to its protective effects in liver IRI [26].…”

Effect of Melatonin on Casein Expression in Buffalo Mammary Epithelial Cells

“…In bovines, major growth factors including insulin, prolactin, leptin, growth hormone and insulin-like growth factor increase protein synthesis through mTOR pathway. Recently, the role of melatonin in protecting the primodial follicles to oxidative stress via mTOR pathway has been described in rat ovaries (Behram-Kandemir et al, 2017). Similarly, melatonin induced cell death via the PI3K/Akt/mTOR pathway is accounted in melanoma cells (Kim et al, 2014).…”