Melatonin protects against ovarian damage by inhibiting autophagy in granulosa cells in rats

Liu, Yan; Zhu, Xihe; Wu, Chunli; Yan, Liang; Zhao, Wenjie; Li, Yanmin

doi:10.1016/j.clinsp.2022.100119

Cited by 7 publications

(2 citation statements)

References 41 publications

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“…In previous study, melatonin inhibited autophagy in mouse granulosa cells cultured in vitro (Shen et al., 2018). In rats, this hormone inhibits autophagy in rat ovarian granulosa cells through activation of the PI3K/Akt/mTOR pathway (Liu et al., 2022). In growing follicles, the TZPs between granulosa cells and oocytes allow the transfer of small metabolites, RNA, and signalling factors, ensuring proper oocyte development (Anderson & Albertini, 1976; Kidder & Vanderhyden, 2010).…”

Section: Discussionmentioning

confidence: 99%

Melatonin improves the viability and ultrastructure of bovine oocyte‐granulosa complexes of in vitro cultured early antral follicles

Silva,

Nascimento,

Costa

et al. 2024

Reprod Domestic Animals

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This study aims to investigate the effects of melatonin on follicular growth, viability and ultrastructure, as well as on the levels of mRNA for antioxidant enzymes, reactive oxygen species (ROS) and meiotic progression in oocytes from in vitro cultured bovine early antral follicles. To this end, isolated early antral follicles (500–600 μm) were cultured in TCM‐199+ alone or supplemented with 10−6, 10−7 or 10−8 M melatonin at 38.5°C with 5% CO2 for 8 days. Follicle diameters were evaluated at days 0, 4 and 8 of culture. At the end of culture, ultrastructure, chromatin configuration, viability (calcein‐AM and ethidium homodimer‐1 staining), and the levels of ROS and mRNA for catalase (CAT), superoxide dismutase (SOD) and peroxiredoxin 6 (PRDX6) and glutathione peroxidase (GPx) were investigated in oocyte‐granulosa cell complexes (OGCs). The results showed that early antral follicles cultured with 10−6 and 10−8 M melatonin had a progressive and significant increase in their diameters throughout the culture period (p < .05). Additionally, oocytes from follicles cultured with 10−7 or 10−8 M melatonin had increased fluorescence for calcein‐AM, while those cultured with 10−6 or 10−7 M had reduced fluorescence for ethidium homodimer‐1. Different from follicles cultured in other treatments, those cultured with 10−8 M melatonin had well‐preserved ultrastructure of oocyte and granulosa cells. Melatonin, however, did not influence the levels of ROS, the mitochondrial activity, oocyte meiotic resumption and expression mRNA for SOD, CAT, GPX1 and PRDX6. In conclusion, the presence of 10−8 M melatonin in culture medium improves viability and preserves the ultrastructure of oocyte and granulosa cells of early antral follicles cultured in vitro.

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Section: Discussionmentioning

confidence: 99%

Melatonin improves the viability and ultrastructure of bovine oocyte‐granulosa complexes of in vitro cultured early antral follicles

Silva,

Nascimento,

Costa

et al. 2024

Reprod Domestic Animals

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show abstract

“…This hormone has antioxidant activities of scavenging free radicals and reducing oxidative stress injuries in human oocytes and granulosa cells [122]. Melatonin's ability to protect the ovarian reserve against ovarian damage caused by gonadotoxic chemotherapies was recently proposed: Liu et al demonstrated Melatonin inhibits granulosa cell autophagy by activating the PI3K/Akt/MTOR signaling pathway, thereby exerting a protective effect against ovarian damage [123]. Barberino et al have shown that pretreatment with Melatonin prevents PMF loss and reduces apoptosis and oxidative damage in the mouse ovary following exposure to Cy [124].…”

Section: Prevention Of Chemotherapy-induced Ovarian Damagementioning

confidence: 99%

Overactivation or Apoptosis: Which Mechanisms Affect Chemotherapy-Induced Ovarian Reserve Depletion?

Kashi,

Meirow

2023

IJMS

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Dormant primordial follicles (PMF), which constitute the ovarian reserve, are recruited continuously into the cohort of growing follicles in the ovary throughout female reproductive life. Gonadotoxic chemotherapy was shown to diminish the ovarian reserve pool, to destroy growing follicle population, and to cause premature ovarian insufficiency (POI). Three primary mechanisms have been proposed to account for this chemotherapy-induced PMF depletion: either indirectly via over-recruitment of PMF, by stromal damage, or through direct toxicity effects on PMF. Preventative pharmacological agents intervening in these ovotoxic mechanisms may be ideal candidates for fertility preservation (FP). This manuscript reviews the mechanisms that disrupt follicle dormancy causing depletion of the ovarian reserve. It describes the most widely studied experimental inhibitors that have been deployed in attempts to counteract these affects and prevent follicle depletion.

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Ochratoxin A induces mitochondrial dysfunction, oxidative stress, and apoptosis of retinal ganglion cells (RGCs), leading to retinal damage in mice

Fu,

Chen,

Yang

2024

Int Ophthalmol

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Purpose Ochratoxin A (OTA) contamination of food and feed is a serious problem worldwide. OTA is considered a carcinogen and immunotoxic, nephrotoxic, and neurotoxic mycotoxin. The present study aims to determine the toxic effects of OTA on retinal ganglion cells (RGCs) and assess the resulting impairment of retinal function in mice. Methods RGC-5 cells were exposed to OTA (100 and 200 μg/L) for 3 days, and the mice were fed OTA-contain (100 and 200 μg/kg) diets for 4 weeks. Antioxidant indices were detected by spectrophotometer. The apoptosis of RGC-5 cells was determined by flow cytometry. Mitochondrial morphology and mitochondrial membrane potential were detected by immunofluorescence. RGC survival was determined by immunofluorescence staining with Brn3a. Flash electroretinography (ERG) was conducted to assess visual function. Results The oxidative-antioxidant balance suggested that OTA-induced severe oxidative stress, including increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels in the OTA-exposed RGC-5 cells, and the reduced activity of superoxide dismutase (SOD) and glutathione-S-transferase (GST) in the OTA exposed group. Furthermore, OTA exposure led to remarkable apoptosis in RGC-5 cells. The mitochondrial detection showed that OTA caused significant mitochondrial membrane potential reduction and mitochondrial fragmentation, which may be the cause of apoptosis of RGC-5 cells. Additionally, in vivo experiments demonstrated that OTA resulted in significant death of RGCs and subsequent retinal dysfunction in mice. Conclusion Ochratoxin A induces mitochondrial dysfunction, oxidative stress, and RGCs death in mice.

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Melatonin protects against ovarian damage by inhibiting autophagy in granulosa cells in rats

Cited by 7 publications

References 41 publications

Melatonin improves the viability and ultrastructure of bovine oocyte‐granulosa complexes of in vitro cultured early antral follicles

Melatonin improves the viability and ultrastructure of bovine oocyte‐granulosa complexes of in vitro cultured early antral follicles

Overactivation or Apoptosis: Which Mechanisms Affect Chemotherapy-Induced Ovarian Reserve Depletion?

Ochratoxin A induces mitochondrial dysfunction, oxidative stress, and apoptosis of retinal ganglion cells (RGCs), leading to retinal damage in mice

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