Maternal pineal melatonin in gestation and lactation physiology, and in fetal development and programming

Gomes, Patrícia Rodrigues Lourenço; Motta-Teixeira, Lívia Clemente; Gallo, Camila Congentino; Buonfiglio, Daniella do Carmo; Camargo, Ludmilla Scodeler de; Quintela, Telma; Reíter, Russel J.; Amaral, Fernanda Gaspar do; Cipolla‐Neto, José

doi:10.1016/j.ygcen.2020.113633

Cited by 32 publications

(34 citation statements)

References 162 publications

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“…A feature of our model is that melatonin is injected to the pregnant rat during the late fetal life and not to the neonatal rat. Previous data demonstrated that melatonin freely crossed over placenta 26 . Low-dose of melatonin, i.e., 0.1 mg/kg bolus plus 0,1 mg/kg/h over 6 h, administered to pregnant sheep experiencing umbilical cord occlusion showed a reduction of microglia activation and a restoration of immature OLs within periventricular white matter 27 .…”

Section: Discussionmentioning

confidence: 98%

Partial protective effects of melatonin on developing brain in a rat model of chorioamnionitis

Favrais

Saliba

Savary

et al. 2021

Sci Rep

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Melatonin has shown promising neuroprotective effects due to its anti-oxidant, anti-inflammatory and anti-apoptotic properties, making it a candidate drug for translation to humans in conditions that compromise the developing brain. Our study aimed to explore the impact of prenatal melatonin in an inflammatory/infectious context on GABAergic neurons and on oligodendrocytes (OLs), key cells involved in the encephalopathy of prematurity. An inflammatory/infectious agent (LPS, 300 μg/kg) was injected intraperitoneally (i.p.) to pregnant Wistar rats at gestational day 19 and 20. Melatonin (5 mg/kg) was injected i.p. following the same schedule. Immunostainings focusing on GABAergic neurons, OL lineage and myelination were performed on pup brain sections. Melatonin succeeded in preventing the LPS-induced decrease of GABAergic neurons within the retrospenial cortex, and sustainably promoted GABAergic neurons within the dentate gyrus in the inflammatory/infectious context. However, melatonin did not effectively prevent the LPS-induced alterations on OLs and myelination. Therefore, we demonstrated that melatonin partially prevented the deleterious effects of LPS according to the cell type. The timing of exposure related to the cell maturation stage is likely to be critical to achieve an efficient action of melatonin. Furthermore, it can be speculated that melatonin exerts a modest protective effect on extremely preterm infant brains.

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Section: Discussionmentioning

confidence: 98%

Partial protective effects of melatonin on developing brain in a rat model of chorioamnionitis

Favrais

Saliba

Savary

et al. 2021

Sci Rep

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“…The amplitude and duration of the nocturnal rise of melatonin were more obvious during late pregnancy than during early or mid pregnancy (Tamura et al, 2008). The concentration reaches the peak just before parturition time and then returns to the usual level immediately after giving birth(Gomes et al, 2021). Maternal melatonin can enter fetal circulation, providing photoperiodic information and regulating fetal physiological functions (Gomes et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…The concentration reaches the peak just before parturition time and then returns to the usual level immediately after giving birth(Gomes et al, 2021). Maternal melatonin can enter fetal circulation, providing photoperiodic information and regulating fetal physiological functions (Gomes et al, 2021). Moreover, melatonin was also reported to be highly secreted by placental villous trophoblasts throughout the whole pregnancy (Gomes et al, 2021), promoting syncytium formation (Soliman et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Melatonin inhibits embryonic rat H9c2 cells growth through induction of apoptosis and cell cycle arrest via PI3K‐AKT signaling pathway

Zhao

Xia

et al. 2021

Birth Defects Research

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Background Our recent epidemiological study revealed that maternal sleep during the periconceptional period should be involved in the risk of congenital heart disease (CHD) in offspring. Melatonin, a sleep related hormone, has been suggested to play a crucial role in embryonic development based on the emerging evidence. In this study, we set out to assess the effect of melatonin on the embryonic cardiac cell growth and to explore the underlying mechanisms. Methods We observed the effect of different gradient doses of melatonin as 10, 100, or 1,000 μM on cell proliferation in H9c2 embryonic rat cardiac cells. Furthermore, flow cytometry was applied to evaluate the impact on apoptosis and cell cycle. RNA‐seq was conducted to screen the changes in expression of mRNA and signaling pathways. Quantitative Real‐Time‐PCR (qRT‐PCR) was then conducted to validate the results. Results It was observed that melatonin could inhibit H9c2 cell growth, at the doses of 100 and 1,000 μM, but not at 10 μM. Moreover, melatonin ranged from 100 to 1,000 μM could instigate cell cycle arrest at G1 phase and simulate apoptosis, in a dose‐dependent manner. In addition, melatonin was found to down‐regulate the expression of a number of genes, which are related to heart development (SPARC, IFITM3, TNNT2, LOX), and PI3K‐Akt signaling pathway activation (FN1, HSP90B1, THBS1, MFGE8, and CLU). Conclusions Our findings suggested that high level of melatonin could be capable of inhibiting growth through the induction of apoptosis and cell cycle arrest via PI3K‐AKT signaling pathway, thereby interfering with embryonic heart development. Considering this study is based on H9c2 embryonic rat cardiac cells, future additional studies using human embryonic cardiac cell are warranted.

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“…Melatonin (N-acetyl-5-methoxytryptamine) is a small indoleamine produced by the pineal gland predominantly during the dark phase of the circadian cycle [ 6 , 10 ]. Melatonin can be produced by immune cells and in many peripheral tissues, including male and female reproductive organs [ 11 ] and exerts pleiotropic bioactivities [ 12 ]. Indeed, it is a broad-spectrum antioxidant, free radical scavenger and an anti-inflammatory molecule [ 13 , 14 , 15 , 16 ] that regulates a number of physiological processes, including reproduction.…”

Section: Introductionmentioning

confidence: 99%

“…First, it is a scavenger for ROS when it is found in low concentration in blood, and when its concentration is elevated, it induces the expression of antioxidant genes such as glutathione peroxidase (GPx), leading to high levels of GSH. This double role is crucial for embryo development since it reduces the levels of ROS in the placenta and embryo environment, allowing the foetus to develop in an environment where oxidative stress is abundant [ 11 ]. Moreover, melatonin has pleiotropic effects on different steps of inflammation, as demonstrated by the proinflammatory role at an early phase of inflammation through activation of cytokines release, such as IL-1 and tumour necrosis factor-alpha (TNF-α) [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Association of Melatonin Administration in Pregnant Ewes with Growth, Redox Status and Immunity of Their Offspring

Bouroutzika

Ciliberti

Caroprese

et al. 2021

Animals

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In this study, the effects of melatonin treatment on growth, redox status and immunity in prenatally stressed newborn lambs were evaluated. Thirty-seven newborn lambs were allocated into two groups (melatonin-MEL and control-CON), based on whether their mothers were treated with melatonin implants or not, respectively. All pregnant ewes were exposed to heat stress. The body weight of lambs was recorded at birth (L0), and then on days 15 (L15) and 40 (L40). Redox biomarkers [total antioxidant capacity (TAC), glutathione (GSH), thiobarbituric acid reactive substances (TBARS)] were assayed in blood samples collected from lambs on days L0, L1, L2, L5, L10 and L40. Chemical analysis and antioxidant capacity were evaluated in colostrum and milk samples collected at the same time points with blood samples. Cytokines (IL-1β, IL-6, IL-10, IFN-γ) and immunoglobulin (IgG) were assayed in blood and colostrum samples collected from ewes on days L0 and L1, and in lambs’ blood on days L0, L1 and L2. The results revealed that body weight gain of newborn lambs did not differ between the two groups (p > 0.05). Better redox status was found in MEL lambs until L2, as well as higher antioxidant capacity in the colostrum of MEL ewes compared to CON ones on day L0 (p < 0.05). In MEL ewes’ colostrum, higher protein content was measured on day L0 and higher fat content on L1 compared to CON group (p < 0.05). The highest level of IL-6 was found in MEL ewes on L1, with a concomitant increase of IL-10 level in MEL lambs in comparison to CON lambs on L2. Moreover, CON colostrum resulted in a higher level of IL-10 within time, coupled with an increased level of IgG found in lambs’ plasma on L2 (p = 0.04). This study indicated that melatonin could be administered as antioxidant and immune-modulatory regime in prenatally stressed offspring in order to cope with the crucial first days of their life. This effect of melatonin was also amplified by crosstalk between IL-6, IL-10 and IgG production, resulting in an improved quality of produced milk.

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Maternal pineal melatonin in gestation and lactation physiology, and in fetal development and programming

Cited by 32 publications

References 162 publications

Partial protective effects of melatonin on developing brain in a rat model of chorioamnionitis

Partial protective effects of melatonin on developing brain in a rat model of chorioamnionitis

Melatonin inhibits embryonic rat H9c2 cells growth through induction of apoptosis and cell cycle arrest via PI3K‐AKT signaling pathway

Association of Melatonin Administration in Pregnant Ewes with Growth, Redox Status and Immunity of Their Offspring

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