Melatonin regulates oxidative stress and apoptosis in fetal hearts of pinealectomised RUPP rats

Doğanlar, Oğuzhan; Doğanlar, Zeynep Banu; Ovalı, Mehmet Akif; Güçlü, Orkut; Demir, Ufuk; Doğan, Ayten; Uzun, Metehan

doi:10.1080/10641955.2020.1802595

Cited by 5 publications

(6 citation statements)

References 58 publications

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“…Unfortunately, clinical trials in PE patients and animal models have demonstrated that melatonin exerts a relatively weak effect on the alleviation of hypertension and proteinuria. Further, long‐term melatonin supplementation also results in decreased fetal birth weight 9,11,13,31–34,58,59 . The elucidation of the orchestrated feedback network comprising T 0 , E 2 , and melatonin in the present study sheds light on the underlying mechanisms responsible for this effect.…”

Section: Discussionmentioning

confidence: 54%

“…Further, long-term melatonin supplementation also results in decreased fetal birth weight. 9,11,13,[31][32][33][34]58,59 The elucidation of the orchestrated feedback network comprising T 0 , E 2 , and melatonin in the present study sheds light on the underlying mechanisms responsible for this effect. As summarized in Figure 7, in PE placenta, a decrease in melatonin levels is, at least in part, the consequence of androgen excess and the subsequent repression of E 2 -GPER1-PKA signaling.…”

Section: Discussionmentioning

confidence: 69%

“…However, most clinical studies and animal experiments have yielded disappointing results. 9,11,[31][32][33][34] For instance, while melatonin supplementation reduces the need for higher doses of antihypertensive medication, it also leads to lower fetal birth weight and exerts an insignificant effect on repressing the production of soluble fms-like tyrosine kinase (sFlt-1) and soluble endoglin (sEng). 34 sFlt-1 and sEng are antagonistic receptors for vascular endothelial growth factor/placental growth factor (PlGF) and TGF-β, respectively.…”

Section: Introductionmentioning

confidence: 99%

“…Considering the common reduction of melatonin in PE patients and its potential to reduce blood pressure through antioxidant properties, such as decreasing intracellular superoxide anion and renal MDA levels, or elevating erythrocyte glutathione peroxidase activity, 30 melatonin supplementation has been proposed as an intervention for PE. However, most clinical studies and animal experiments have yielded disappointing results 9,11,31–34 . For instance, while melatonin supplementation reduces the need for higher doses of antihypertensive medication, it also leads to lower fetal birth weight and exerts an insignificant effect on repressing the production of soluble fms‐like tyrosine kinase (sFlt‐1) and soluble endoglin (sEng) 34 .…”

Section: Introductionmentioning

confidence: 99%

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Orchestrated feedback regulation between melatonin and sex hormones involving GPER1‐PKA‐CREB signaling in the placenta

Shao,

Yang,

Liu

et al. 2023

Journal of Pineal Research

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Maintaining placental endocrine homeostasis is crucial for a successful pregnancy. Pre‐eclampsia (PE), a gestational complication, is a leading cause of maternal and perinatal morbidity and mortality. Aberrant elevation of testosterone (T0) synthesis, reduced estradiol (E2), and melatonin productions have been identified in preeclamptic placentas. However, the precise contribution of disrupted homeostasis among these hormones to the occurrence of PE remains unknown. In this study, we established a strong correlation between suppressed melatonin production and decreased E2 as well as elevated T0 synthesis in PE placentas. Administration of the T0 analog testosterone propionate (TP; 2 mg/kg/day) to pregnant mice from E7.5 onwards resulted in PE‐like symptoms, along with elevated T0 production and reduced E2 and melatonin production. Notably, supplementation with melatonin (10 mg/kg/day) in TP‐treated mice had detrimental effects on fetal and placental development and compromised hormone synthesis. Importantly, E2, but not T0, actively enhanced melatonin synthetase AANAT expression and melatonin production in primary human trophoblast (PHT) cells through GPER1‐PKA‐CREB signaling pathway. On the other hand, melatonin suppressed the level of estrogen synthetase aromatase while promoting the expressions of androgen synthetic enzymes including 17β‐HSD3 and 3β‐HSD1 in PHT cells. These findings reveal an orchestrated feedback mechanism that maintains homeostasis of placental sex hormones and melatonin. It is implied that abnormal elevation of T0 synthesis likely serves as the primary cause of placental endocrine disturbances associated with PE. The suppression of melatonin may represent an adaptive strategy to correct the imbalance in sex hormone levels within preeclamptic placentas. The findings of this study offer novel evidence that identifies potential targets for the development of innovative therapeutic strategies for PE.

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Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Orchestrated feedback regulation between melatonin and sex hormones involving GPER1‐PKA‐CREB signaling in the placenta

Shao,

Yang,

Liu

et al. 2023

Journal of Pineal Research

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“…Melatonin also decreased hypertension, placental IL-6 expression, oxidative stress and proteinuria in murine models of PE [69,70]. In offspring, maternal melatonin treatment ameliorated fetal heart damage caused by reduced uterine perfusion pressure (RUPP) [71]. Melatonin also had a global epigenetic effect during nephrogenesis and restored the ADMA-NO balance in the kidney in a rat model [72,73].…”

Section: Melatoninmentioning

confidence: 90%

Effects of Antioxidant Intake on Fetal Development and Maternal/Neonatal Health during Pregnancy

et al. 2022

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During pregnancy, cycles of hypoxia and oxidative stress play a key role in the proper development of the fetus. Hypoxia during the first weeks is crucial for placental development, while the increase in oxygen due to the influx of maternal blood stimulates endothelial growth and angiogenesis. However, an imbalance in the number of oxidative molecules due to endogenous or exogenous factors can overwhelm defense systems and lead to excessive production of reactive oxygen species (ROS). Many pregnancy complications, generated by systemic inflammation and placental vasoconstriction, such as preeclampsia (PE), fetal growth restriction (FGR) and preterm birth (PTB), are related to this increase of ROS. Antioxidants may be a promising tool in this population. However, clinical evidence on their use, especially those of natural origin, is scarce and controversial. Following PRISMA methodology, the current review addresses the use of natural antioxidants, such as epigallocatechin gallate (EGCG), melatonin and resveratrol (RESV), as well as other classical antioxidants (vitamin C and E) during the prenatal period as treatment of the above-mentioned complications. We review the effect of antioxidant supplementation on breast milk in lactating mothers.

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Crocin treatment exerts anti-inflammatory and anti-oxidative effects in liver tissue damage of pinealectomized diabetic rats

Karayakali

Altınöz

Elbe

et al. 2023

Environ Sci Pollut Res

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Melatonin regulates oxidative stress and apoptosis in fetal hearts of pinealectomised RUPP rats

Cited by 5 publications

References 58 publications

Orchestrated feedback regulation between melatonin and sex hormones involving GPER1‐PKA‐CREB signaling in the placenta

Orchestrated feedback regulation between melatonin and sex hormones involving GPER1‐PKA‐CREB signaling in the placenta

Effects of Antioxidant Intake on Fetal Development and Maternal/Neonatal Health during Pregnancy

Crocin treatment exerts anti-inflammatory and anti-oxidative effects in liver tissue damage of pinealectomized diabetic rats

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