Melatonin potentially acts directly on swine ovary by modulating granulosa cell function and angiogenesis

Basini, Giuseppina; Bussolati, Simona; Ciccimarra, Roberta; Grasselli, Francesca

doi:10.1071/rd16513

Cited by 38 publications

(18 citation statements)

References 43 publications

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“…There was no difference in FF concentrations of estradiol and progesterone between the placebo and melatonin groups, suggesting that melatonin is not significantly associated with the synthesis of these hormones in the follicle. This is in contrast to previous findings in swine models ( 24 ).…”

Section: Discussioncontrasting

confidence: 99%

Melatonin in Assisted Reproductive Technology: A Pilot Double-Blind Randomized Placebo-Controlled Clinical Trial

et al. 2018

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Purpose: To explore in a small pilot study whether oral melatonin, administered during ovarian stimulation increases clinical pregnancy rate (CPR) after IVF and what dose might be most effective.Methods: Pilot double-blind, dose-finding, placebo-controlled randomized clinical trial in private IVF clinics in Australia between September 2014 and September 2016. One hundred and sixty women having their first cycle of IVF or ICSI were randomized to receive placebo (n = 40), melatonin 2 mg (n = 41), melatonin 4 mg (n = 39), or melatonin 8 mg (n = 40) twice per day (BD) during ovarian stimulation. The primary outcome was CPR. Secondary outcomes included serum and follicular fluid (FF) melatonin concentrations, oocyte/embryo quantity/quality, and live birth rate (LBR). Analysis was performed using the intention-to-treat principle.Results: There was no difference in CPR or LBR between any of the four groups (p = 0.5). When all the doses of melatonin were compared as a group with placebo, the CPR was 21.7% for the former and 15.0% for the latter [OR 1.57 (95% CI 0.59, 4.14), p = 0.4]. There were also no differences between the groups in total oocyte number, number of MII oocytes, number of fertilized oocytes, or the number or quality of embryos between the groups. This is despite mean FF melatonin concentration in the highest dose group (8 mg BD) being nine-fold higher compared with placebo (P < 0.001).Conclusion: No significant differences were observed in CPR or oocyte and embryo parameters despite finding a nine-fold increase in FF melatonin concentration. However, this study was not sufficiently powered to assess differences in CPR and therefore, these results should be interpreted with caution. Because this was a small RCT, a beneficial effect of melatonin on IVF pregnancy rates cannot be excluded and merits confirmation in further, larger clinical trials. ANZCTR (http://www.anzctr.org.au/ Project ID: ACTRN12613001317785).

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Section: Discussioncontrasting

confidence: 99%

Melatonin in Assisted Reproductive Technology: A Pilot Double-Blind Randomized Placebo-Controlled Clinical Trial

et al. 2018

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“…Papers performed in various mammalian species reported that melatonin protects the adult ovary from the harmful effects of a variety of treatments and compounds, including nicotine [ 30 , 32 – 34 , 36 , 42 ]. Melatonin is able to scavenge the most toxic free radical as a robust antioxidant [ 59 ].…”

Section: Discussionmentioning

confidence: 99%

Protective effects of melatonin against nicotine-induced disorder of mouse early folliculogenesis

Wang

Sun

Han

et al. 2018

Aging

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In this paper, we show that neonatal mice injected for five consecutive days with nicotine display impaired germ cell cyst breakdown and primordial follicle assembly resulting in decreased ovarian reserve lasting until sex maturation age. The effects of nicotine on the pups ovaries were associated with decreased expression of oocyte specific genes such as Nobox, Lhx8, Figlα and Sohlh2. Moreover, the ovaries of pups injected with nicotine showed increased level of cell oxidative stress and autophagic markers (upregulation of AMPKα-1, increased ratio LC3-II/LC3-I, downregulation of AKT and mTOR). Noteworthy, all these effects were counteracted by the administration of the hormone melatonin in 1 μM. In vitro culture of 0 dpp ovaries for 5 days in the presence of 10 μM nicotine reproduced its effect on germ cell cyst breakdown and primordial follicle assembly, furthermore it also revealing about 20% reduction of somatic cells proliferation, and these effects was prevented when melatonin was added to the medium. Taken together these results show that nicotine exposure can adversely affect the establishment of the ovarian reserve in the mouse likely by locally inducing cellular stress altering the primordial follicle assembly and that melatonin, however, is able to counteract such effects.

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“…α7 receptors are also involved in angiogenic and neurogenic activity, and have anti-apoptotic effects. As pineal MT upregulates the α7nAChR over the circadian rhythm [ 26 ], the role of the α7nAChR in modulation of the various facets of embryogenesis will be important to determine.…”

Section: Melatonin Synthesis and Signaling Ways Of Embryogenesismentioning

confidence: 99%

Melatonin, Its Beneficial Effects on Embryogenesis from Mitigating Oxidative Stress to Regulating Gene Expression

Ivanov

Mazzoccoli

Anderson³

et al. 2021

IJMS

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Embryogenesis is a complex multi-stage process regulated by various signaling molecules including pineal and extrapineal melatonin (MT). Extrapineal MT is found in the placenta and ovaries, where it carries out local hormonal regulation. MT is necessary for normal development of oocytes, fertilization and subsequent development of human, animal and avian embryos. This review discusses the role of MT as a regulator of preimplantation development of the embryo and its implantation into endometrial tissue, followed by histo-, morpho- and organogenesis. MT possesses pronounced antioxidant properties and helps to protect the embryo from oxidative stress by regulating the expression of the NFE2L2, SOD1, and GPX1 genes. MT activates the expression of the ErbB1, ErbB4, GJA1, POU5F1, and Nanog genes which are necessary for embryo implantation and blastocyst growth. MT induces the expression of vascular endothelial growth factor (VEGF) and its type 1 receptor (VEGF-R1) in the ovaries, activating angiogenesis. Given the increased difficulties in successful fertilization and embryogenesis with age, it is of note that MT slows down ovarian aging by increasing the transcription of sirtuins. MT administration to patients suffering from infertility demonstrates an increase in the effectiveness of in vitro fertilization. Thus, MT may be viewed as a key factor in embryogenesis regulation, including having utility in the management of infertility.

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Melatonin potentially acts directly on swine ovary by modulating granulosa cell function and angiogenesis

Cited by 38 publications

References 43 publications

Melatonin in Assisted Reproductive Technology: A Pilot Double-Blind Randomized Placebo-Controlled Clinical Trial

Melatonin in Assisted Reproductive Technology: A Pilot Double-Blind Randomized Placebo-Controlled Clinical Trial

Protective effects of melatonin against nicotine-induced disorder of mouse early folliculogenesis

Melatonin, Its Beneficial Effects on Embryogenesis from Mitigating Oxidative Stress to Regulating Gene Expression

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