RESUMO
Disruption of the maternal environment during pregnancy is a key contributor to offspring diseases that develop in adult life. To explore the impact of chronodisruption during pregnancy in primates, we exposed pregnant capuchin monkeys to constant light (eliminating the maternal melatonin rhythm) from the last third of gestation to term. Maternal temperature and activity circadian rhythms were assessed as well as the newborn temperature rhythm. Additionally we studied the effect of daily maternal melatonin replacement during pregnancy on these rhythms. Ten pregnant capuchin monkeys were exposed to constant light from 60% of gestation to term. Five received a daily oral dose of melatonin (250 µg kg/body weight) at 1800 h (LL+Mel) and the other five a placebo (LL). Six additional pregnant females were maintained in a 14â¶10 light:dark cycles and their newborns were used as controls (LD). Rhythms were recorded 96 h before delivery in the mother and at 4-6 days of age in the newborn. Exposure to constant light had no effect on the maternal body temperature rhythm however it delayed the acrophase of the activity rhythm. Neither rhythm was affected by melatonin replacement. In contrast, maternal exposure to constant light affected the newborn body temperature rhythm. This rhythm was entrained in control newborns whereas LL newborns showed a random distribution of the acrophases over 24-h. In addition, mean temperature was decreased (34.0±0.6 vs 36.1±0.2°C, in LL and control, respectively P<0.05). Maternal melatonin replacement during pregnancy re-synchronized the acrophases and restored mean temperature to the values in control newborns. Our findings demonstrate that prenatal melatonin is a Zeitgeber for the newborn temperature rhythm and supports normal body temperature maintenance. Altogether these prenatal melatonin effects highlight the physiological importance of the maternal melatonin rhythm during pregnancy for the newborn primate.
Assuntos
Ritmo Circadiano/efeitos da radiação , Luz , Mães , Temperatura , Animais , Animais Recém-Nascidos , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Comportamento Animal/efeitos da radiação , Cebus , Ritmo Circadiano/efeitos dos fármacos , Feminino , Masculino , Exposição Materna/efeitos adversos , Melatonina/farmacologia , Gravidez , Terceiro Trimestre da Gravidez/efeitos dos fármacos , Terceiro Trimestre da Gravidez/fisiologia , Terceiro Trimestre da Gravidez/efeitos da radiação , Fatores de TempoRESUMO
OBJECTIVE: The study was conducted to evaluate the effect of Carraguard vaginal gel containing 0.75 mg of levonorgestrel (CARRA/LNG gel) administered in a single dose at different stages of follicle development over subsequent follicle rupture and hormonal levels. METHOD: Randomized, blinded, cross-over study comparing the effects of a single administration of CARRA/LNG gel or Carraguard (CARRA) gel. Twenty-four healthy women were enrolled in two centers. The gels were administered when the follicle had reached diameters of 12-14, 15-17 and > or =18 mm in eight women each. Volunteers were followed for one treatment, one washout cycle and a second treatment cycle. Follicle rupture or nonrupture was assessed by transvaginal ultrasound. Luteinizing hormone, estradiol and progesterone levels were measured daily for 5 days following treatment, and three times per week until menses. RESULTS: No follicular rupture within the 5-day period following administration was observed in 74% and 30% of the CARRA/LNG and CARRA gel treatment cycles, respectively, while ovulation was documented in 4% and 61%, respectively. The overall proportion of cycles with lack of follicular rupture or ovulatory dysfunction (follicle rupture preceded by an inadequate LH surge) was 96% for CARRA/LNG and 39% in the CARRA gel cycles. CONCLUSION: Single vaginal administration of 0.75 mg LNG in CARRA gel in the late follicular phase is effective for interfering with the ovulatory process.
Assuntos
Anticoncepcionais Femininos/administração & dosagem , Levanogestrel/administração & dosagem , Folículo Ovariano/efeitos dos fármacos , Ovulação/efeitos dos fármacos , Administração Intravaginal , Adulto , Anticoncepção Pós-Coito , Anticoncepcionais Femininos/efeitos adversos , Anticoncepcionais Femininos/sangue , Estudos Cross-Over , Feminino , Humanos , Levanogestrel/efeitos adversos , Levanogestrel/sangue , Ciclo Menstrual/efeitos dos fármacosRESUMO
We tested the hypothesis that in primates, maternal melatonin restrains fetal and newborn adrenal cortisol production. A functional G-protein-coupled MT1 membrane-bound melatonin receptor was detected in 90% gestation capuchin monkey fetal adrenals by (a) 2-[(125)I] iodomelatonin binding (K(d), 75.7 +/- 6.9 pm; B(max), 2.6 +/- 0.4 fmol (mg protein)(-1)), (b) cDNA identification, and (c) melatonin inhibition of adrenocorticotrophic hormone (ACTH)- and corticotrophin-releasing hormone (CRH)-stimulated cortisol but not of dehydroepiandrosterone sulphate (DHAS) production in vitro. Melatonin also inhibited ACTH-induced 3beta-hydroxysteroid dehydrogenase mRNA expression. To assess the physiological relevance of these findings, we next studied the effect of chronic maternal melatonin suppression (induced by exposure to constant light during the last third of gestation) on maternal plasma oestradiol during gestation and on plasma cortisol concentration in the 4- to 6-day-old newborn. Constant light suppressed maternal melatonin without affecting maternal plasma oestradiol concentration, consistent with no effect on fetal DHAS, the precursor of maternal oestradiol. However, newborns from mothers under constant light condition had twice as much plasma cortisol as newborns from mothers maintained under a normal light-dark schedule. Newborns from mothers exposed to chronic constant light and daily melatonin replacement had normal plasma cortisol concentration. Our results support a role of maternal melatonin in fetal and neonatal primate cortisol regulation.
Assuntos
Glândulas Suprarrenais/embriologia , Cebus/fisiologia , Hidrocortisona/antagonistas & inibidores , Melatonina/fisiologia , Prenhez/metabolismo , 3-Hidroxiesteroide Desidrogenases/genética , Hormônio Adrenocorticotrópico/farmacologia , Animais , Animais Recém-Nascidos/sangue , Cebus/metabolismo , Hormônio Liberador da Corticotropina/farmacologia , Sulfato de Desidroepiandrosterona/metabolismo , Desenvolvimento Embrionário e Fetal , Estradiol/sangue , Feminino , Feto/anatomia & histologia , Feto/metabolismo , Hidrocortisona/sangue , Luz , Melatonina/sangue , Melatonina/efeitos da radiação , Concentração Osmolar , Gravidez , Prenhez/sangue , Receptores de Melatonina/metabolismo , Transcrição Gênica/efeitos dos fármacosRESUMO
During gestation, the perinatal neuroendocrine axis keeps clock time. In primates, the suprachiasmatic nucleus (biological clock in mammals), shows oscillatory function by midgestation. There is evidence in rodents that the mother, during pregnancy, entrains the fetal suprachiasmatic nucleus (SCN) and newborn circadian rhythms. We are investigating the role of maternal melatonin as an entraining signal for the newborn circadian time-keeping system in the Cebus apella (New World non-human primate). Twenty-four hour rhythms of temperature and cortisol are present in the 4 days old C. apella newborn. Preliminary data suggests that inhibition of maternal melatonin by exposing pregnant females to constant light alters these rhythms. We have found binding sites for melatonin and expression of mRNA for Mel 1A receptor in hypothalamus, kidney and testis. These preliminary results suggest that maternal melatonin may play a role in relating the perinatal circadian time-keeping system to environmental signals.