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Melatonin 1A and 1B Receptors’ Expression Decreases in the Placenta of Women with Fetal Growth Restriction

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Abstract

Melatonin and its metabolites prevent oxidative stress and apoptosis, and it is actively produced by the placenta during pregnancy. Melatonin 1A and 1B receptors are present in human villous trophoblastic cells. We aimed to investigate the expression of melatonin 1A and 1B receptors in human placental tissue in the case of placental insufficiency manifested as the intrauterine growth restriction syndrome of the fetus (IUGR). Thirty-two pregnant women aged 18–36 with placental insufficiency manifested at the term 36 weeks of gestation as the IUGR syndrome (the estimated fetal weight less than the 3rd percentile) were included in the experimental group; all their babies had the diagnosis confirmed at birth, which occurred after 37 weeks of gestation. The control group consisted of 30 women with uncomplicated pregnancy of the same term. Pieces of the placental tissue were obtained after deliveries, and melatonin 1A and 1B receptors were immunoassayed; the richness of melatonin receptors in the placental tissue was estimated on the basis of immunohistochemical (IHC) staining of receptors, calculated in the IHC image score. The optical density of melatonin 1A receptors in the placentas obtained from women whose pregnancies were complicated with IUGR was significantly lower than that in the placentas from uncomplicated pregnancies: generally in the trophoblast, it was 0.095 ± 0.0009 IHC image score (in the control group, 0.194 ± 0.0015, p < 0.0001); in the apical parts of the syncytiotrophoblast, 0.108 ± 0.0016 IHC image score (in the control group, 0.221 ± 0.0013, p < 0.0001); and in the stromal cells of placental villi, 0.112 ± 0.0013 IHC image score (in the control group, 0.156 ± 0.0011, p < 0.0001). The optical density of melatonin 1B receptors in placentas obtained from women whose pregnancies were complicated with IUGR was also lower than that in the placentas from uncomplicated pregnancies: generally in the trophoblast, it was 0.165 ± 0.0019 IHC image score (in the control group, 0.231 ± 0.0013, p < 0.0001), and in the apical parts of the syncytiotrophoblast, 0.188 ± 0.0028 IHC image score (in the control group, 0.252 ± 0.0009, p < 0.0001). There was no difference found in the optical density of melatonin 1B receptors in the stromal cells of placental villi between the two groups: in the experimental group, 0.109 ± 0.006 IHC image score, and in the control group, 0.114 ± 0.0011 (p = 0.65). Melatonin receptors 1A and 1B are significantly less expressed in the placental tissue in the case that pregnancy is complicated with placental insufficiency, manifested as the intrauterine growth restriction syndrome of the fetus.

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Acknowledgments

The authors express the heartiest acknowledgments to the patients who agreed to participate in the study and to the reviewers of the paper for their altruistic intellectual job as experts in the field.

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Authors and Affiliations

  1. Higher State Educational Establishment of Ukraine “Bukovinian State Medical University”, Chernivtsi, Ukraine

    Andrii M. Berbets, Igor S. Davydenko, Adrian M. Barbe, Olena M. Albota & Oleksandr M. Yuzko

  2. National Pirogov Memorial Medical University, Vinnytsia, Ukraine

    Dmytro H. Konkov

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  1. Andrii M. Berbets
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Contributions

Andrii Berbets was responsible for the clinical management of the patients, sample processing, searching in databases, data analysis, and drafting of the manuscript. Igor Davydenko processed the immunoassaying of the samples. Adrian Barbe conducted the statistical analysis and drafting of the manuscript. Dmytro Konkov analyzed the data. Olena Albota was responsible for the recruiting of the patients. Oleksandr Yuzko was the project leader and was responsible for finalizing the manuscript.

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The study was approved by the Biological and Medical Ethics Committee of the Higher State Educational Establishment of Ukraine “Bukovinian State Medical University” (the minutes no. 3 dated March 30, 2017) and was carried out strictly in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving humans.

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Berbets, A.M., Davydenko, I.S., Barbe, A.M. et al. Melatonin 1A and 1B Receptors’ Expression Decreases in the Placenta of Women with Fetal Growth Restriction. Reprod. Sci. 28, 197–206 (2021). https://doi.org/10.1007/s43032-020-00285-5

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