Circadian timekeeping during pregnancy: Endogenous phase relationships between maternal plasma hormones and the maternal body temperature rhythm in pregnant rhesus monkeys

Nine pregnant rhesus monkeys maintained in constant low level lighting (5 Lux) from 56-80 days gestation (dGA) onward were studied to assess the presence or absence of circadian maternal body temperature and maternal plasma hormone variations. Maternal arterial blood samples were taken every 4 h in six monkeys (105-120 dGA) for 48-56 h and every 2 h in three monkeys (108-115 dGA) for 60 h. Maternal intraabdominal temperature was recorded continuously. Cosinor analysis was used to determine circadian rhythmicity. Individual endogenous timekeeping was demonstrated by 1) free-running circadian variations in maternal body temperature in all nine animals, 2) consistent internal acrophase relationships between the maternal body temperature and maternal plasma cortisol rhythm, and 3) idiosyncrasy of the temporal relationship of detectable rhythms to the external environment in individual animals. Only one animal had a significant maternal plasma ACTH rhythm, whereas the presence of 24-h variations in the other hormones varied in individual animals. The mean ± SD acrophase profiles in hours from the temperature acrophase in those animals who showed significant rhythms were 19.7 ± 0.6 (n = 8) for cortisol, 19.4 ± 2.4 (n = 6) for dehydroepiandrosterone sulfate, 8.3 + 1.1 (n = 6) for progesterone, and 18.9 ± 1.6 (n = 3) for estradiol. We conclude that 24-h variations in maternal plasma hormones are truly endogenously generated and not passively dependent on the light-dark cycle. The maternal circadian system regulates the 24 h temporal organization of endogenous plasma hormone variations. We hypothesize that rhythms in cortisol, dehydroepiandrosterone sulfate, progesterone, and estradiol during pregnancy are directly or indirectly governed by the maternal hypothalamus via the circadian oscillatory output of the maternal adrenal.