Effects of Melatonin on Early Pregnancy in Mouse: Involving the Regulation of StAR, Cyp11a1, and Ihh Expression

Guan, Shengyu; Xie, Lu; Ma, Teng; Lv, Dongying; Wang, Jing; Tian, Xiaoli; Song, Yukun; Liu, Zhiping; Xiao, Xiang-Hong; Liu, Guoshi

doi:10.3390/ijms18081637

Cited by 20 publications

(17 citation statements)

References 54 publications

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“…Melatonin is produced within the retina and is known to stimulate sirtuin activity in mitochondria, which deacetylates many of the enzymes involved within the TCA cycle. Previous studies have shown that supplementation with melatonin has no known toxicity affects when taken during pregnancy in both humans and mice [79][80][81]. Additionally, resveratrol is a plant-derived polyphenol that has been widely studied for its potential benefits as a protective agent against cancers, mutagenesis, and a variety of other biological functions [81].…”

Section: Discussionmentioning

confidence: 99%

Metabolite therapy guided by liquid biopsy proteomics delays retinal neurodegeneration

Wert

Vélez

Vijayalakshmi

et al. 2019

Preprint

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One Sentence Summary: The study shows protein and metabolite pathways affected during neurodegeneration and that replenishing metabolites provides a neuroprotective effect on the retina. Abstract: 244Main Text: 9,039References: 83 AbstractNeurodegenerative diseases are debilitating, incurable disorders caused by progressive neuronal cell death.Retinitis pigmentosa (RP) is a blinding neurodegenerative disease that results in retinal photoreceptor cell death and progresses to the loss of the entire neural retinal network. We previously found that proteomic analysis of the adjacent vitreous serves as way to indirectly biopsy the neural retina and identify changes in the retinal proteome. We therefore analyzed protein expression in liquid vitreous biopsies from autosomal recessive retinitis pigmentosa (arRP) patients with PDE6A mutations and arRP mice with Pde6ɑ mutations. Proteomic analysis of retina and vitreous samples identified molecular pathways affected at the onset of photoreceptor cell death. Based on affected molecular pathways, arRP mice were treated with a ketogenic diet or metabolites involved in fatty-acid synthesis, oxidative phosphorylation, and the tricarboxylic acid (TCA) cycle. Dietary supplementation of a single metabolite, ɑ-ketoglutarate, increased docosahexaeonic acid (DHA) levels, provided neuroprotection, and enhanced visual function in arRP mice. A ketogenic diet delayed photoreceptor cell loss, while vitamin B supplementation had a limited effect. Finally, desorption electrospray ionization mass spectrometry imaging (DESI-MSI) revealed restoration of key metabolites that correlated with our proteomic findings: pyrimidine and purine metabolism (uridine, dihydrouridine, and thymidine), glutamine and glutamate (glutamine/glutamate conversion), and succinic and aconitic acid (TCA cycle). This study demonstrates that replenishing TCA cycle metabolites via oral supplementation prolongs vision and provides a neuroprotective effect on the photoreceptor cells and inner retinal network.

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Section: Discussionmentioning

confidence: 99%

Metabolite therapy guided by liquid biopsy proteomics delays retinal neurodegeneration

Wert

Vélez

Vijayalakshmi

et al. 2019

Preprint

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“…In general terms, reproductive disorders triggered through hormonal alterations represent one of the main causes of infertility [ 20 ]; this is why many studies have been focused on understanding melatonin functions during pregnancy [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

From Implantation to Birth: Insight into Molecular Melatonin Functions

Carlomagno¹,

Minini

Tilotta³

et al. 2018

IJMS

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Melatonin is a lipophilic hormone synthesized and secreted mainly in the pineal gland, acting as a neuroendocrine transducer of photoperiodic information during the night. In addition to this activity, melatonin has shown an antioxidant function and a key role as regulator of physiological processes related to human reproduction. Melatonin is involved in the normal outcome of pregnancy, beginning with the oocyte quality, continuing with embryo implantation, and finishing with fetal development and parturition. Melatonin has been shown to act directly on several reproductive events, including folliculogenesis, oocyte maturation, and corpus luteum (CL) formation. The molecular mechanism of action has been investigated through several studies which provide solid evidence on the connections between maternal melatonin secretion and embryonic and fetal development. Melatonin administration, reducing oxidative stress and directly acting on its membrane receptors, melatonin thyroid hormone receptors (MT1 and MT2), displays effects on the earliest phases of pregnancy and during the whole gestational period. In addition, considering the reported positive effects on the outcomes of compromised pregnancies, melatonin supplementation should be considered as an important tool for supporting fetal development, opening new opportunities for the management of several reproductive and gestational pathologies.

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“…Melatonin seems to improve uterine receptivity and embryo implantation in early pregnancy by stimulating the development of the corpus luteum before gestation. A recent study by Guan et al [63] demonstrated that melatonin given orally to mice for 14 days prior to mating was essential to improve implantation by lowering E2 secretion while upregulating the P4-regulated Indian Hedgehog (Ihh) factor expression in the endometrium on day 7.5 of gestation. After successful mating, melatonin treatment for 14 days increased P4 secretion and promoted enhanced expression of LIF.…”

Section: Figurementioning

confidence: 99%

Melatonin Promotes Uterine and Placental Health: Potential Molecular Mechanisms

Chuffa

Lupi

Cucielo

et al. 2019

IJMS

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The development of the endometrium is a cyclic event tightly regulated by hormones and growth factors to coordinate the menstrual cycle while promoting a suitable microenvironment for embryo implantation during the “receptivity window”. Many women experience uterine failures that hamper the success of conception, such as endometrium thickness, endometriosis, luteal phase defects, endometrial polyps, adenomyosis, viral infection, and even endometrial cancer; most of these disturbances involve changes in endocrine components or cell damage. The emerging evidence has proven that circadian rhythm deregulation followed by low circulating melatonin is associated with low implantation rates and difficulties to maintain pregnancy. Given that melatonin is a circadian-regulating hormone also involved in the maintenance of uterine homeostasis through regulation of numerous pathways associated with uterine receptivity and gestation, the success of female reproduction may be dependent on the levels and activity of uterine and placental melatonin. Based on the fact that irregular production of maternal and placental melatonin is related to recurrent spontaneous abortion and maternal/fetal disturbances, melatonin replacement may offer an excellent opportunity to restore normal physiological function of the affected tissues. By alleviating oxidative damage in the placenta, melatonin favors nutrient transfer and improves vascular dynamics at the uterine–placental interface. This review focuses on the main in vivo and in vitro functions of melatonin on uterine physiological processes, such as decidualization and implantation, and also on the feto-maternal tissues, and reviews how exogenous melatonin functions from a mechanistic standpoint to preserve the organ health. New insights on the potential signaling pathways whereby melatonin resists preeclampsia and endometriosis are further emphasized in this review.

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Effects of Melatonin on Early Pregnancy in Mouse: Involving the Regulation of StAR, Cyp11a1, and Ihh Expression

Cited by 20 publications

References 54 publications

Metabolite therapy guided by liquid biopsy proteomics delays retinal neurodegeneration

Metabolite therapy guided by liquid biopsy proteomics delays retinal neurodegeneration

From Implantation to Birth: Insight into Molecular Melatonin Functions

Melatonin Promotes Uterine and Placental Health: Potential Molecular Mechanisms

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