ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Developmental Endocrinology
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1640635
This article is part of the Research TopicPlacental Dysfunction in Pregnancy: Endocrine and Metabolic Mechanisms in Preeclampsia, FGR, Diabetes, and HypertensionView all 10 articles
MELATONIN MODULATES THE GENE EXPRESSION OF WEE1-KINASE AND CLOCK GENES. A CROSSTALK BETWEEN THE MOLECULAR CLOCKS OF THE PLACENTA?
Provisionally accepted
Carlos Venegas
Kevins Jara-MedinaNicole CuetoGerardo Cabello-Guzman
Constanza LagunasLuis Lillo
Francisco J Valenzuela-Melgarejo*- Universidad del Bio-Bio - Sede Chillan, Chillán, Chile
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Background: The circadian system organizes during 24 hours the temporal variations in biological processes such as the cell cycle, metabolism, and hormone production. This occurs by a transcriptional/translational feedback loop of core clock genes named BMAL1, PER1-3, and CRY1-2. The CLOCK-BMAL1 complex regulates clock-controlled genes like WEE1 kinase, a key modulator of mitotic entry and placental cell proliferation. Objective: We aimed to identify temporally regulated gene expression patterns in the human placenta using bioinformatics analysis of available microarrays in GEO datasets, and to validate selected findings in cultured placental explants. Methods: Temporal microarray data from the Gene Expression Omnibus (GEO) were analyzed to identify circadian and cell cycle-related genes. Selected targets were validated in vitro using explant cultures of human placenta sampled every 4 hours for 36 hours, with or without 10 nM melatonin. Results: We observed rhythmic expression of BMAL1, PER1, PER2, and WEE1 in human placental explants, consistent with the temporal patterns detected in silico. Melatonin treatment suppressed the circadian oscillation of BMAL1, PER2, and WEE1. Interestingly, the placenta produced melatonin steadily over 36 hours, and exogenous melatonin did not alter this production.
Keywords: Melatonin, Placenta, clock gene, Cell Cycle, Pregnancy
Received: 04 Jun 2025; Accepted: 14 Oct 2025.
Copyright: © 2025 Venegas, Jara-Medina, Cueto, Cabello-Guzman, Lagunas, Lillo and Valenzuela-Melgarejo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Francisco J Valenzuela-Melgarejo, bioquimico79@gmail.com
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