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Maternal Melatonin Effects on Clock Gene Expression in a Nonhuman Primate Fetus

Departamento de Ciencias Fisiológicas (C.T.F., V.R., C.M., F.J.V., F.T., M.S.-F.), Facultad de Ciencias Biológicas, Departamento de Endocrinología (C.C.), Facultad de Medicina, Pontificia Universidad Católica de Chile, Casilla 114D, Santiago, Chile; Unidad de Medicina Materno-Fetal (A.G.), Centro Especializado de Vigilancia Materno Fetal, Departamento de Obstetricia y Ginecología, Clinica Las Condes, Santiago, Chile; and Department of Women’s Health Arrowhead Regional Medical Center (G.J.V.), Colton, California 92324

Address all correspondence and requests for reprints to: María Serón-Ferré, Departamento de Ciencias Fisiológicas, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Casilla (P.O. Box) 114D, Santiago, Chile. E-mail: mseron{at}puc.cl.

In the adult mammal the circadian system, which allows predictive adaptation to daily environmental changes, comprises peripheral oscillators in most tissues, commanded by the suprachiasmatic nucleus (SCN) of the hypothalamus. The external environment of the fetus is provided by its mother. In primates, maternal melatonin is a candidate to entrain fetal circadian rhythms, including the SCN rhythms of metabolic activity. We found in the 90% of gestation capuchin monkey fetus expression of the clock genes Bmal-1, Per-2, Cry-2, and Clock in the SCN, adrenal, pituitary, brown fat, and pineal. Bmal-1, Per-2, and the melatonin 1 receptor (MT1) showed a robust oscillatory expression in SCN and adrenal gland, whereas a circadian rhythm of dehydroepiandrosterone sulphate was found in plasma. Maternal melatonin suppression changed the expression of Bmal-1, Per-2, and MT1 in the fetal SCN. These effects were reversed by maternal melatonin replacement. In contrast, neither maternal melatonin suppression nor its replacement had effects on the expression of Per-2 and Bmal-1 or MT1 in the fetal adrenal gland or the circadian rhythm of fetal plasma dehydroepiandrosterone sulphate. Our data suggest that maternal melatonin is a Zeitgeber for the fetal SCN but probably not for the adrenal gland.

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