Melatonin and the light-dark cycle separately influence daily behavioral and hormonal rhythms in the pregnant ewe and sheep fetus.

Abstract

We have studied the effects of independently altering the time of darkness and the phase of the daily melatonin rhythm during a 12-h photoperiod on the diurnal rhythms of fetal breathing movements (FBMs), low voltage electrocortical activity, and maternal and fetal plasma concentrations of PRL. Thirteen pregnant ewes were pinealectomized at 99-100 days gestation and held under a normal lighting regime (12-h photoperiod, lights off at 1900 h) until 135 days gestation. All ewes were then exposed to an altered lighting regime (12-h photoperiod, lights off at 1100 h) until 145 days gestation. Six of these ewes were infused with melatonin (12-15 micrograms/h iv) from 1100 h for 12 h each day between 125 and 135 days gestation while in the normal lighting regime, and from 1900 h while in the altered lighting regime. The remaining seven ewes were infused with saline at corresponding times. Infusion of melatonin produced a significant daily rhythm in maternal and fetal melatonin concentrations; concentrations were highest throughout the 12-h infusion period in each lighting regime. In the normal lighting regime (i.e. lights off at 1900 h) the peak incidence of FBM occurred at between 1000 and 1300 h in the ewes infused with saline or melatonin. Under the altered lighting conditions there was no 24-h variation in the incidence of FBMs in the saline-infused group, but a significant daily variation was present in the melatonin-infused group with peak incidence occurring at 1900-2200 h. The daily variation in maternal PRL concentrations was not affected by changes in the time of onset of melatonin infusion but was different in each of the two lighting regimes. In the normal lighting regime, PRL concentrations were highest at 2100 h (56.2 +/- 21.6 ng/ml) whereas in the altered lighting conditions the peak in maternal PRL occurred at 1700 h (90.4 +/- 25.1 ng/ml). The daily variation in fetal PRL concentrations was also not affected by changes in the time of onset of melatonin infusion but was different in the two lighting regimes; in the normal lighting regime, fetal PRL reached a peak (13.0 +/- 3.7 ng/ml) at 0100-0300 h whereas in the altered lighting regime the peak (29.2 +/- 9.8 ng/ml) occurred at 1700-2100 h. We have presented evidence therefore that the daily melatonin rhythm may entrain the daily rhythm in fetal breathing activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Maternal melatonin selectively inhibits cortisol production in the primate fetal adrenal gland

“…At birth, newborns had similar body weights and appeared clinically healthy, suggesting that melatonin deprivation or replacement did not cause major alterations of the fetal environment. This is consistent with observations in the fetal sheep, in which maternal pinealectomy (Yellon & Longo, 1988; McMillen & Nowak, 1989), maternal exposure to constant light (Stark & Daniel, 1989; Parraguez et al 1996), or administration of melatonin (Serón‐Ferré et al 1989; Houghton et al 1993) did not modify fetal cardiorespiratory variables.…”

“…Maternal melatonin crosses the placenta unaltered, so that fetuses are exposed to the maternal melatonin rhythm (Yellon & Longo, 1988; McMillen & Nowak, 1989). This avenue for melatonin to mediate interactions between maternal and fetal physiological functions has been explored mostly at the level of the fetal suprachiasmatic nucleus (Naitoh et al 1998), and in the control of fetal circadian rhythms (Serón‐Ferré et al 1989; McMillen et al 1990; Houghton et al 1993; Serón‐Ferré et al 1993). However, maternal melatonin may be involved in a wider array of fetal functions, given the presence of melatonin receptors in diverse tissues of the developing sheep (Helliwell & Williams, 1994), in the fetal human kidney (Drew et al 1998) and in several areas of the fetal human brain (Thomas et al 2002).…”

The development of melatonin-binding sites in the ovine fetus

“…In the adenohypophysis, specific labelling is restricted mainly to the pars tuberahs (PT) with scattered labelling over the pars distalis of vasopressin concentration, found in the cerebrospinal fluid of the fetal sheep, is disrupted (Stark & Daniel 1989). Also, maternal pinealectomy has been shown to alter the daily pattern of fetal breathing (McMillen et al 1990) and this effect is mediated via the maternal melatonin signal (Houghton et al 1993). It appears, therefore, that maternal melatonin not only influences seasonal neuroendocnne functions but may also influence both neuronal and somatic circadian rhythms in the fetal sheep.…”

Variations from morning to afternoon of middle cerebral and umbilical artery blood flow, and fetal heart rate variability, and fetal characteristics in the normally developing fetus

“…6 Current findings suggest that fetal circadian rhythms are derived from the maternal melatonin cycle [7][8][9] but the circadian pattern of maternal glucocorticoid levels may also influence emerging fetal pituitary and adrenal function. 6 Current findings suggest that fetal circadian rhythms are derived from the maternal melatonin cycle [7][8][9] but the circadian pattern of maternal glucocorticoid levels may also influence emerging fetal pituitary and adrenal function.…”