Portal de Periódicos da CAPES

Carta Acesso aberto Produção Nacional Revisado por pares

BIBTEX RIS

Expression of the melatonin receptor and tryptophan hydroxylase in placentas of the fetus with intra-uterine stress

2009; Elsevier BV; Volume: 147; Issue: 2 Linguagem: Inglês

10.1016/j.ejogrb.2009.07.015

1872-7654

Rosana Rosa Miranda Corrêa, Sue Ellen Gonçalves Barrilari, Camila S.O. Guimarães, Renata Calciolari Rossi, Janaínna Grazielle Pacheco Olegário, Camila Lourencini Cavellani, Flávia Aparecida de Oliveira, Ana Karina Marques Salge, Vicente P. A. Teixeira, Eumenia Castro,

Neuroscience of respiration and sleep

We found that melatonin is the only hormone of the neuroendocrine system present in all systems, demonstrating synchronized biological rhythmic coordination and it is considered to be one of the most powerful natural antioxidants and is capable of controlling stress [[1]Tamura H. Nakamura Y. Terron M.P. et al.Melatonin and pregnancy in the human.Reprod Toxicol. 2008; 25: 291-303Crossref PubMed Scopus (173) Google Scholar]. Although the mechanisms regarding its control of fetal circadian rhythm have been described, how melatonin acts in fetal stress conditions has not been fully established [[2]Gitto E. Romeo C. Reiter R.J. et al.Melatonin reduces oxidative stress in surgical neonates.J Pediatr Surg. 2004; 39: 184-189Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar]. Moreover, some studies identify the presence of melatonin in the placenta [[3]Kvetnoy I. Extrapineal melatonin in pathology: new perspectives for diagnosis, prognosis and treatment of illness.Neuro Endocrinol Lett. 2002; 23: 92-96PubMed Google Scholar], but no information regarding the mechanisms of synthesis, the production cells or alterations possibly associated with the conditions of fetal stress are available in the literature. The aim of this study was to evaluate enzyme expression in relation to melatonin synthesis in placenta, comparing the variations in relation to the cause of death of children autopsied in the perinatal period. We obtained 18 placentas from cases of fetal/newborn autopsy, divided into congenital anomalies and perinatal stress (PS) or chronic stress, included cases with ascending infection and chronic perinatal hypoxia/anoxia. Perinatal stress was defined when the thymus, adrenal and liver presented morphological alterations compatible with intrauterine stress. The placenta was also examined in these cases to confirm the autopsy findings. The clinical data on these patients was not available because most of these patients did not have a prenatal follow up. The adrenal presented increasing amounts of coarse lipid droplets in the fetal cortex. The thymus was evaluated for the presence of phagocytosis (positive cells for CD68 antibody), cortex thickness and the weight for involution. In the liver we evaluated the amount of intra-hepatic hematopoiesis. After macroscopic analysis, the fragment processed for immunohistochemistry for detecting tryptophan hydroxylase (TH), and melatonin receptors (MT1A), and percentage of positive immunoreactive areas per field analyzed by KS-300, Kontrol-Zeiss®. Immunohistochemistry using the anti-TH antibody demonstrated a cytoplasmatic staining pattern in the cytotrophoblast, the syncytiotrophoblast and in the inflammatory cells (polymorphonuclear) of the intervillous space, while MT1A antibody demonstrated staining for the same structures and also for vascular endothelium. The percentage of positive immunoreactive areas per field (PAF) for TH and MT1A expression was significantly greater in cases of ascending infection for MT1A and perinatal hypoxia/anoxia for TH, when compared with the cases with congenital anomalies (Table 1). No significant difference occurred between the positive cellular area PAF for TH expression between full term and premature gestations. In contrast, the positive PAF for MT1A expression was significantly greater in full term gestations (p < 0.001). A significant positive correlation occurred between gestational age and the PAF for MT1A expression in the placenta (Pr: 0.705; p = 0.007).Table 1Comparison of the percentage of positive immunoreactive areas per field (PAF) for the expression of the MT1A and tryptophan hydroxylase between the different groups of the causes of death diagnosed in the perinatal autopsies.Groupn (%)Tryptophan hydroxylase (% PAF)MT1A (% PAF)MedianMinimumMaximumMedianMinimumMaximumCA5 (27.8)6.212.49.99.327.611.8PHA6 (33.3)5.33.310.914.028.620.6AI7 (38.9)8.114.512.210.76.813.7Total18 (100)TestH = 12.839; p = 0.002H = 15.759; p < 0.0011,2Dunn: p < 0.05. CA, congenital anomalies; PHA, perinatal hypoxia/anoxia; AI, ascending infection. Open table in a new tab 1,2Dunn: p < 0.05. CA, congenital anomalies; PHA, perinatal hypoxia/anoxia; AI, ascending infection. In the placenta, studies have demonstrated the expression of melatonin receptors and precursory enzymes [[4]Lanoix D. Beghdadi H. Lafond J. et al.Human placental trophoblasts synthesize melatonin and express its receptors.J Pineal Res. 2008; 45: 50-60Crossref PubMed Scopus (100) Google Scholar] using a polymerase chain reaction. However, there are no studies in the literature describing the in situ location of these markers. Immunohistochemical staining of the vascular endothelium and inflammatory cells is described in other organs [[3]Kvetnoy I. Extrapineal melatonin in pathology: new perspectives for diagnosis, prognosis and treatment of illness.Neuro Endocrinol Lett. 2002; 23: 92-96PubMed Google Scholar]. Regarding the trophoblast, anti-TH and MT1A were shown when using immunohistochemistry, reinforcing the hypothesis of other studies that suggested a regulation capacity for melatonin of the placenta function in a paracrine and autocrine manner [[4]Lanoix D. Beghdadi H. Lafond J. et al.Human placental trophoblasts synthesize melatonin and express its receptors.J Pineal Res. 2008; 45: 50-60Crossref PubMed Scopus (100) Google Scholar]. The PAF for anti-TH and MT1A were significantly greater in cases of intrauterine stress. The cells involved in melatonin production can be considered part of the neuroendocrine system, with a direct antioxidant function and, indirectly, provide protection against lesions caused by free radical production [[5]Okatani Y. Wakatsuki A. Shinohara K. et al.Melatonin stimulates glutathione peroxidase activity in human chorion.J Pineal Res. 2001; 30: 199-205Crossref PubMed Scopus (67) Google Scholar]. The results of this study, about the increase in melatonin receptors, as well as the enzyme produced as part of its synthesis, in cases of PS, are consistent with a placental protection mechanism. The present study still demonstrated that, regardless of the cause of intrauterine stress, an increase in melatonin intra-hepatic hemapoiesis synthesis occurs, verified by TH expression and by its action, through greater MT1A expression in the placenta. MT1A expression was significantly greater in full term gestations, showing a significant positive correlation with gestational age. This data suggests a more mature immune response to intrauterine stress. This difference in receptor expression could be one of the factors that explains the improved therapeutic response and evolution of full term neonates in comparison to premature newborns in response to perinatal stress situations. Financial Support: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), Fundação de Ensino e Pesquisa de Uberaba (FUNEPU).