Melatonin improves placental efficiency and birth weight and increases the placental expression of antioxidant enzymes in undernourished pregnancy

Abstract

Melatonin participates in circadian, seasonal and reproductive physiology. Melatonin also acts as a potent endogenous antioxidant by scavenging free radicals and upregulating antioxidant pathways. The placenta expresses melatonin receptors and melatonin protects against oxidative damage induced in rat placenta by ischemia-reperfusion. One of the most common complications in pregnancy is a reduction in fetal nutrient delivery, which is known to promote oxidative stress. However, whether melatonin protects placental function and fetal development in undernourished pregnancy is unknown. Here, we investigated the effects of maternal treatment with melatonin on placental efficiency, fetal growth, birth weight and protein expression of placental oxidative stress markers in undernourished pregnancy. On day 15 of pregnancy, rats were divided into control and undernourished pregnancy (35% reduction in food intake), with and without melatonin treatment (5 microg/mL drinking water). On day 20 of gestation, fetal biometry was carried out, the placenta was weighed and subsequently analyzed by Western blot for xanthine oxidase, heat shock protein (HSP) 27 and 70, catalase, manganese superoxide dismutase (Mn-SOD) and glutathione peroxidase 1 (GPx-1). A separate cohort was allowed to deliver to assess effects on birth weight. Maternal undernutrition led to a fall in placental efficiency, disproportionate intrauterine growth retardation and a reduction in birth weight. Maternal treatment with melatonin in undernourished pregnancy improved placental efficiency and restored birth weight, and it increased the expression of placental Mn-SOD and catalase. The data show that in pregnancy complicated by undernutrition, melatonin may improve placental efficiency and birth weight by upregulating placental antioxidant enzymes.

Fetal undernutrition is associated with perinatal sex-dependent alterations in oxidative status

“…Furthermore, there is evidence that melatonin might be a key hormone in fetal life, improving utero-placental hemodynamics and reducing placental oxidative stress in pregnancies complicated with IUGR [59,60] and in animal models of maternal undernutrition [61,62]. The lower melatonin levels in male MUN offspring was not paralleled by a reduction in TAC values and therefore, its contribution in the pool of direct scavengers might not be relevant in this model.…”

Melatonin supplementation alters uteroplacental hemodynamics and fetal development in an ovine model of intrauterine growth restriction

“…All scans ended before the dark phase (19:00). Ultrasound evaluations took place on days 48 (baseline measurements), 50,60,70,80,90,100, and 110 of gestation. Color Doppler ultrasound scans were performed at a constant flow gain setting of 10 and flow filter setting of 2.…”

“…Therapeutic supplements thought to target placental blood flow and nutrient delivery to the fetus have been shown to increase fetal growth in animal models of intrauterine growth restriction (IUGR) (50,52,64); however, few studies have addressed uteroplacental hemodynamics in models of improved fetal growth. Moreover, fetal organ development and functional capacity may be altered by supplementing the dam with melatonin throughout gestation.…”

“…Interestingly, melatonin receptors have been identified in the developing nephron of human fetal kidneys (13); however, an in vivo physiological role of these melatonin receptor pathways within the fetus remains elusive. Recently, melatonin supplementation was shown to negate the decreased birth weight in nutrient-restricted rats (50), which was attributed to increased placental antioxidant enzyme expression. Therefore, dietary melatonin treatment during a compromised pregnancy may improve placental nutrient transfer capacity, fetal growth, and fetal organ development by decreasing maternal oxidative stress and/or by melatonin receptor mediated pathways.…”

Mechanisms of Melatonin-Induced Protection in the Brain of Late Gestation Fetal Sheep in Response to Hypoxia

“…Others have shown that melatonin reduces oxidative stress and cell damage in the immature fetal sheep brain in response to severe hypoxia [20], and, in fetal and neonatal rats, melatonin improves indices of brain mitochondrial injury and protects against hippocampal cell loss following cerebral ischemia and reperfusion [24,25,26]. Melatonin also demonstrates anti-inflammatory properties, stimulates placental expression of antioxidant enzymes, increases placental efficiency and enhances umbilical flow in compromised pregnancies [27,28,29]; all actions which are likely to protect the developing fetus.…”