Placental melatonin production and melatonin receptor expression are altered in preeclampsia: new insights into the role of this hormone in pregnancy

Abstract

The melatonin system in preeclamptic pregnancies has been largely overlooked, especially in the placenta. We have previously documented melatonin production and expression of its receptors in normal human placentas. In addition, we and others have shown a beneficial role of melatonin in placental and fetal functions. In line with this, decreased maternal blood levels of melatonin are found in preeclamptic compared with normotensive pregnancies. However, melatonin production and expression of its receptors in preeclamptic compared with normotensive pregnancy placentas has never been examined. This study compares (i) melatonin-synthesizing enzyme expression and activity, (ii) melatonin and serotonin, melatonin's immediate precursor, levels and (iii) expression of MT1 and MT2 melatonin receptors in placentas from preeclamptic and normotensive pregnancies. Protein and mRNA expression of aralkylamine N-acetyltransferase (AANAT) and hydroxyindole O-methyltransferase (HIOMT), the melatonin-synthesizing enzymes, as well as MT1 and MT2 receptors were determined by RT-qPCR and Western blot, respectively. The activities of melatonin-synthesizing enzymes were assessed by radiometric assays while melatonin levels were determined by LC-MS/MS. There is a significant inhibition of AANAT, melatonin's rate-limiting enzyme, expression and activity in preeclamptic placentas, correlating with decreased melatonin levels. Likewise, MT1 and MT2 expression is significantly reduced in preeclamptic compared with normotensive pregnancy placentas. We propose that reduced maternal plasma melatonin levels may be an early diagnostic tool to identify pregnancies complicated by preeclampsia. This study indicates a clinical utility of melatonin as a potential treatment for preeclampsia in women where reduced maternal plasma levels have been identified.

Salivary melatonin levels and sleep-wake rhythms in pregnant women with hypertensive and glucose metabolic disorders: A prospective analysis

“…Melatonin reportedly protects cellular apoptosis in the placenta by acting as an antioxidant (34) and a free radical scavenger (35). Melatonin also inhibits the vasospasticity of the umbilical artery (36), and when administered, possibly prevents the risk of preeclampsia (37). These findings suggest that the risk of preeclampsia is higher when melatonin secretion is decreased.…”

Caloric restriction, resveratrol and melatonin: Role of SIRT1 and implications for aging and related-diseases

“…This indoleamine is synthesized from the essential amino acid l-tryptophan by the action of four enzymes: tryptophan hydroxylase, l-aromatic amino acid decarboxylase, N-acetyltransferase and hydroxyindole-O-methyltransferase (also known as acetylserotonin methyltransferase) (Stehle et al, 2011;García et al, 2014). In vertebrates, melatonin is best known as a secretory product of the pineal gland, but it as well as the enzymes that produce it are present in numerous other tissues including retina, skin, immune system, gastrointestinal tract and reproductive tract (Reiter, 1991;Huether et al, 1992;Tan et al, 1999;Stefulj et al, 2001;Slominski et al, 2002;Kleszczynski and Fischer, 2012;Lanoix et al, 2012;Acuña-Castroviejo et al, 2014).…”

Melatonin secretion is impaired in women with preeclampsia and an abnormal circadian blood pressure rhythm

“…In addition, according to Lanoix et al (2012), preeclampsia leads to depressed melatonin levels in the placenta. 45 Reduced melatonin levels in preeclampsia, showed in this study, might be in part due to reduced placental secretion.…”

“…In addition, according to Lanoix et al (2012), preeclampsia leads to depressed melatonin levels in the placenta. 45 Reduced melatonin levels in preeclampsia, showed in this study, might be in part due to reduced placental secretion. Studies in animal models of hypertension in pregnancy suggest that shallow placentation and reduction in uteroplacental perfusion during pregnancy triggers the release of biologically active factors which affect the sympathetic tone and lead to generalized vasoconstriction, hypertension and disturbance of the circadian BP rhythm.…”