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

Abstract

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.

Protective effect of maternal prenatal melatonin administration on rat pups born to mothers submitted to constant light during gestation

“…Constant light has been shown to disrupt the circadian organization in adult rodents due to an individual desynchronization of clock neurons (31). These data agree with those obtained in studies on fetuses of capuchin monkeys from mothers exposed to constant light, which showed a significant alteration of fetal expression of the SCN clock genes Bmal-1 and melatonin-1 receptor (32). Thus, the disruption of pup circadian organization would explain the alteration of mother clock ability to generate circadian signal(s) under adverse effects of prenatal LL.…”

Clock Gene Expression in Adult Primate Suprachiasmatic Nuclei and Adrenal: Is the Adrenal a Peripheral Clock Responsive to Melatonin?

“…To dissect out a hypothalamic block that included the SCN, we relied on our previous experience with the neuroanatomy of the capuchin monkey fetal SCN (17), SCN from different species (24,25) and on the atlas of the Cebus apella by Manocha et al (26). Roughly, the block was 5.5 mm in the anteroposterior plane, 10 mm wide, and 5 mm in the dorsoventral plane.…”

“…clock controlled) genes involved in multiple cellular functions in 24 h in most tissues, resulting in the overt circadian rhythms in the individual (10 -12). Recent studies showed circadian in vivo expression of clock genes in the adrenal gland of adult rhesus monkey and mice (8,(13)(14)(15)(16) and fetal capuchin monkey (17). According to Yoo et al (18), most peripheral tissues show circadian oscillation of clock genes under in vitro conditions; however, this possibility has not been investigated for the adrenal gland.…”

The pattern of melatonin receptor expression in the brain may influence antidepressant treatment

“…In addition to their expression in the suprachiasmatic nucleus (SCN), these receptors are expressed in the mammalian central nervous system (CNS) including in humans [4][5][6][7].…”