Potential adverse effects of antenatal melatonin as a treatment for intrauterine growth restriction: findings in pregnant sheep

Gonzaléz‐Candia, Alejandro; Veliz, Marcelino; Araya, Claudio; Quezada, Sebastián; Ebensperger, Germán; Serón-Ferré, Marı́a; Reyes, Roberto V.; Llanos, Aníbal J.; Herrera, Emílio

doi:10.1016/j.ajog.2016.02.040

Cited by 39 publications

(39 citation statements)

References 61 publications

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“…Although most studies have not found side effects after long-term treatment with melatonin in children [76][77][78] or after maternal or early post-natal life treatment in animals [79][80][81], some studies revealed negative effects of melatonin in developing organisms, such as reductions in litter size, pup growth and weight, increased mortality, and alterations in sexual maturation, fertility and levels of luteinizing hormone [50,[82][83][84][85].…”

Section: Discussionmentioning

confidence: 99%

Pre- and post-natal melatonin administration partially regulates brain oxidative stress but does not improve cognitive or histological alterations in the Ts65Dn mouse model of Down syndrome

Corrales

Parisotto

Vidal

et al. 2017

Behavioural Brain Research

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Melatonin administered during adulthood induces beneficial effects on cognition and neuroprotection in the Ts65Dn (TS) mouse model of Down syndrome. Here, we investigated the effects of pre- and post-natal melatonin treatment on behavioral and cognitive abnormalities and on several neuromorphological alterations (hypocellularity, neurogenesis impairment and increased oxidative stress) that appear during the early developmental stages in TS mice. Pregnant TS females were orally treated with melatonin or vehicle from the time of conception until the weaning of the offspring, and the pups continued to receive the treatment from weaning until the age of 5 months. Melatonin administered during the pre- and post-natal periods did not improve the cognitive impairment of TS mice as measured by the Morris Water maze or fear conditioning tests. Histological alterations, such as decreased proliferation (Ki67+ cells) and hippocampal hypocellularity (DAPI+ cells), which are typical in TS mice, were not prevented by melatonin. However, melatonin partially regulated brain oxidative stress by modulating the activity of the primary antioxidant enzymes (superoxide dismutase in the cortex and catalase in the cortex and hippocampus) and slightly decreasing the levels of lipid peroxidation in the hippocampus of TS mice. These results show the inability of melatonin to prevent cognitive impairment in TS mice when it is administered at pre- and post-natal stages. Additionally, our findings suggest that to induce pro-cognitive effects in TS mice during the early stages of development, in addition to attenuating oxidative stress, therapies should aim to improve other altered processes, such as hippocampal neurogenesis and/or hypocellularity.

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Section: Discussionmentioning

confidence: 99%

Pre- and post-natal melatonin administration partially regulates brain oxidative stress but does not improve cognitive or histological alterations in the Ts65Dn mouse model of Down syndrome

Corrales

Parisotto

Vidal

et al. 2017

Behavioural Brain Research

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“…This effect is associated with improved endothelial function and reversal of fetal hypoxia-induced vascular remodeling; however, melatonin does not prevent FGR. Even more, in a chronic hypoxic sheep model, melatonin decreased maternal oxidative stress but simultaneously enhanced fetal growth restriction [39]. In summary, these data suggest that hypoxia and oxidative stress participate in the genesis of FGR-induced vascular dysfunction.…”

Section: Hypoxia and Oxidative Stress In Fgrmentioning

confidence: 82%

Epigenetic Programming of Cardiovascular Disease by Perinatal Hypoxia and Fetal Growth Restriction

Casanello¹,

Herrera²,

Krause³

2017

Hypoxia and Human Diseases

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Most of the worldwide deaths in patients with non-communicable diseases are due to cardiovascular and metabolic diseases, which are determined by a mix of environmental, genetic and epigenetic factors, and by their interactions. The aetiology of most cardiovascular diseases has been partially linked with in utero adverse conditions that may increase the risk of developing diseases later in life, known as Developmental Origins of Health and Disease (DOHaD). Perinatal hypoxia can program the fetal and postnatal developmental patterns, resulting in permanent modifications of cells, organs and systems function. In spite of the vast evidence obtained from human and animal studies linking development under adverse intrauterine conditions with increased cardiovascular risk, still few is known about the specific effects of intrauterine oxygen deficiency and the related pathogenic mechanisms. Currently, the most accepted processes that program cellular function are epigenetic mechanisms which determine gene expression in a cell-specific fashion. In this chapter we will review the current literature regarding the perinatal exposure to chronic hypoxia and Fetal Growth Restriction (FGR) in humans and animals and how this impinges the cardiovascular physiology through epigenetic, biochemical, morphologic and pathophysiologic modifications that translate into diseases blasting at postnatal life.

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“…Зокрема, розглянуті дані світової літератури щодо застосування мелатоніну, бензодіазепінів, антигістамінних та седативних перпаратів. Щодо мелатоніну: є дані, що цей гормон може викликати зниження маси тіла при народженні та подовження вагітності у піддослідних тварин [2]. Водночас, за даними інших авторів, в США до 1% вагітних жінок приймають мелатонін під час вагітності, як біологічну добавку, оскільки його обіг не регулюється Food and Drugs Administration [1].…”

Section: вступunclassified

Changes of the sleep in pregnant women with intrauterine fetal growth restriction

Berbets¹

2018

Rep. of Vinnytsia Nation. Med. Univ.

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Objective – to study the reasons of appearance, terms of manifestation and types of the sleep disorders in pregnant women with intrauterine growth restriction of fetus. 80 pregnant women with placental insufficiency, manifesting as intrauterine fetal growth restriction (IUGR) of II–III degree in the 3rd pregnancy trimester (study group) and 30 women with normal clinical flow of pregnancy (control group) were questioned. They were asked about pregnancy term when the complains of the sleep disorders were firstly expressed, as well as about types of the sleep disorders and their frequency (in times per week). Questioning showed that pregnant women with IUGR in 86% cases experience the sleep disorders starting from pregnancy term 12–22 weeks (healthy pregnant women — mostly after 30 weeks, 57% cases), more commonly wake up 2 or more times per night (71% of positive answers, in control group – 23%), and 3 or more times per week (78% of positive answers, in control group – 17%). Thus, sleep disorders in pregnant women with IUGR appear earlier and seem to be more expressed then in pregnant women with normal fetal growth. Expression of the complains of insomnia, in our opinion, might be considered as an early diagnostic sign of forming of placental insufficiency, which is later realized as IUGR.

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Potential adverse effects of antenatal melatonin as a treatment for intrauterine growth restriction: findings in pregnant sheep

Cited by 39 publications

References 61 publications

Pre- and post-natal melatonin administration partially regulates brain oxidative stress but does not improve cognitive or histological alterations in the Ts65Dn mouse model of Down syndrome

Pre- and post-natal melatonin administration partially regulates brain oxidative stress but does not improve cognitive or histological alterations in the Ts65Dn mouse model of Down syndrome

Epigenetic Programming of Cardiovascular Disease by Perinatal Hypoxia and Fetal Growth Restriction

Changes of the sleep in pregnant women with intrauterine fetal growth restriction

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