RESUMO
KEY POINTS: Light at night is essential to a 24/7 society, but it has negative consequences on health. Basically, light at night induces an alteration of our biological clocks, known as chronodisruption, with effects even when this occurs during pregnancy. Here we explored the developmental impact of gestational chronodisruption (chronic photoperiod shift, CPS) on adult and fetal adrenal biorhythms and function. We found that gestational chronodisruption altered fetal and adult adrenal function, at the molecular, morphological and physiological levels. The differences between control and CPS offspring suggest desynchronization of the adrenal circadian clock and steroidogenic pathway, leading to abnormal stress responses and metabolic adaptation, potentially increasing the risk of developing chronic diseases. ABSTRACT: Light at night is essential to a 24/7 society, but it has negative consequences on health. Basically, light at night induces an alteration of our biological clocks, known as chronodisruption, with effects even when this occurs during pregnancy. Indeed, an abnormal photoperiod during gestation alters fetal development, inducing long-term effects on the offspring. Accordingly, we carried out a longitudinal study in rats, exploring the impact of gestational chronodisruption on the adrenal biorhythms and function of the offspring. Adult rats (90 days old) gestated under chronic photoperiod shift (CPS) decrease the time spent in the open arm zone of an elevated plus maze to 62% and increase the rearing time to 170%. CPS adults maintained individual daily changes in corticosterone, but their acrophases were distributed from 12.00 h to 06.00 h. CPS offspring maintained clock gene expression and oscillation, nevertheless no daily rhythm was observed in genes involved in the regulation and synthesis of steroids. Consistent with adult adrenal gland being programmed during fetal life, blunted daily rhythms of corticosterone, core clock gene machinery, and steroidogenic genes were observed in CPS fetal adrenal glands. Comparisons of the global transcriptome of CPS versus control fetal adrenal gland revealed that 1078 genes were differentially expressed (641 down-regulated and 437 up-regulated). In silico analysis revealed significant changes in Lipid Metabolism, Small Molecule Biochemistry, Cellular Development and the Inflammatory Response pathway (z score: 48-20). Altogether, the present results demonstrate that gestational chronodisruption changed fetal and adult adrenal function. This could translate to long-term abnormal stress responses and metabolic adaptation, increasing the risk of developing chronic diseases.
Assuntos
Glândulas Suprarrenais/fisiologia , Relógios Circadianos/fisiologia , Feto/fisiologia , Animais , Comportamento Animal , Metilação de DNA , Feminino , Masculino , Gravidez , Ratos Sprague-Dawley , TranscriptomaRESUMO
The adrenal gland in the adult is a peripheral circadian clock involved in the coordination of energy intake and expenditure, required for adaptation to the external environment. During fetal life, a peripheral circadian clock is present in the nonhuman primate adrenal gland. Whether this extends to the fetal adrenal gland like the rat is unknown. Here we explored in vivo and in vitro whether the rat fetal adrenal is a peripheral circadian clock entrained by melatonin. We measured the 24-h changes in adrenal content of corticosterone and in the expression of clock genes Per-2 and Bmal-1 and of steroidogenic acute regulatory protein (StAR), Mt1 melatonin receptor, and early growth response protein 1 (Egr-1) expression. In culture, we explored whether oscillatory expression of these genes persisted during 48 h and the effect of a 4-h melatonin pulse on their expression. In vivo, the rat fetal adrenal gland showed circadian expression of Bmal-1 and Per-2 in antiphase (acrophases at 2200 and 1300 h, respectively) as well as of Mt1 and Egr-1. This was accompanied by circadian rhythms of corticosterone content and of StAR expression both peaking at 0600 h. The 24-h oscillatory expression of Bmal-1, Per-2, StAR, Mt1, and Egr-1 persisted during 48 h in culture; however, the antiphase between Per-2 and Bmal-1 was lost. The pulse of melatonin shifted the acrophases of all the genes studied and restored the antiphase between Per-2 and Bmal-1. Thus, in the rat, the fetal adrenal is a strong peripheral clock potentially amenable to regulation by maternal melatonin.
Assuntos
Glândulas Suprarrenais/metabolismo , Relógios Circadianos/fisiologia , Ritmo Circadiano/fisiologia , Melatonina/sangue , Fatores de Transcrição ARNTL/genética , Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/embriologia , Análise de Variância , Animais , Relógios Circadianos/genética , Corticosterona/sangue , Corticosterona/metabolismo , Proteína 1 de Resposta de Crescimento Precoce/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Técnicas In Vitro , Masculino , Melatonina/farmacologia , Proteínas Circadianas Period/genética , Fosfoproteínas/genética , Gravidez , Ratos , Ratos Sprague-Dawley , Receptor MT1 de Melatonina/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de TempoRESUMO
Lowland mammals at high altitude constrict the pulmonary vessels, augmenting vascular resistance and developing pulmonary arterial hypertension. In contrast, highland mammals, like the llama, do not present pulmonary arterial hypertension. Using wire myography, we studied the sensitivity to norepinephrine (NE) and NO of small pulmonary arteries of fetal llamas and sheep at high altitudes. The sensitivity of the contractile responses to NE was decreased whereas the relaxation sensitivity to NO was augmented in the llama fetus compared to the sheep fetus. Altogether these data show that the fetal llama has a lower sensitivity to a vasoconstrictor (NE) and a higher sensitivity to a vasodilator (NO), than the fetal sheep, consistent with a lower pulmonary arterial pressure found in the neonatal llama in the Andean altiplano. Additionally, we investigated carbon monoxide (CO) in the pulmonary circulation in lowland and highland newborn sheep and llamas. Pulmonary arterial pressure was augmented in neonatal sheep but not in llamas. These sheep had reduced soluble guanylate cyclase and heme oxygenase expression and CO production than at lowland. In contrast, neonatal llamas increased markedly pulmonary CO production and HO expression at high altitude. Thus, enhanced pulmonary CO protects against pulmonary hypertension in the highland neonate. Further, we compared pulmonary vascular responses to acute hypoxia in the adult llama versus the adult sheep. The rise in pulmonary arterial pressure was more marked in the sheep than in the llama. The llama pulmonary dilator strategy may provide insights into new treatments for pulmonary arterial hypertension of the neonate and adult.
Assuntos
Altitude , Animais Recém-Nascidos/fisiologia , Camelídeos Americanos/fisiologia , Feto/fisiologia , Circulação Pulmonar/fisiologia , Carneiro Doméstico/fisiologia , Animais , Pressão Sanguínea/fisiologia , Monóxido de Carbono/metabolismo , Heme Oxigenase-1/metabolismo , Hipertensão Pulmonar/fisiopatologia , Hipóxia/fisiopatologia , Nitroprussiato/farmacologia , Norepinefrina/farmacologia , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/fisiologia , Circulação Pulmonar/efeitos dos fármacos , Resistência Vascular/fisiologia , Vasoconstrição/efeitos dos fármacos , Vasoconstrição/fisiologia , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologiaRESUMO
In nonhuman primates and rodents, melatonin acting directly on the adrenal gland, inhibits glucocorticoid response to ACTH. In these species, an intrinsic adrenal circadian clock is involved in ACTH-stimulated glucocorticoid production. We investigated whether these findings apply to the human adrenal gland by determining i) expression of clock genes in vivo and ii) direct effects of melatonin in ACTH-stimulated adrenal explants over a) expression of the clock genes PER1 (Period 1) mRNA and BMAL1 [Brain-Muscle (ARNT)-like] protein, ACTH-induced steroidogenic acute regulatory protein (StAR), and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) and b) over cortisol and progesterone production. Adrenal tissue was obtained from 6 renal cancer patients undergoing unilateral nephrectomy-adrenalectomy. Expression of the clock genes PER1, PER2, CRY2 (Cryptochrome 2), CLOCK (Circadian Locomotor Output Cycles Kaput) and BMAL1, was investigated by RT-PCR in a normal adrenal and in an adenoma. In independent experiments, explants from 4 normal adrenals were preincubated in culture medium (6 h) followed by 12 h in: medium alone; ACTH (100 nM); ACTH plus melatonin (100 nM); and melatonin alone. The explants' content of PER1 mRNA (real-time PCR) and StAR, 3ß-HSD, BMAL1 (immuno slot-blot), and their cortisol and progesterone production (RIA) were measured. The human adrenal gland expresses the clock genes PER1, PER2, CRY2, CLOCK, and BMAL1. ACTH increased PER1 mRNA, BMAL1, StAR, and 3ß-HSD protein levels, and cortisol and progesterone production. Melatonin inhibited these ACTH effects. Our study demonstrates, for the first time, direct inhibitory effects of melatonin upon several ACTH responses in the human adrenal gland.
Assuntos
Glândulas Suprarrenais/metabolismo , Hormônio Adrenocorticotrópico/metabolismo , Regulação para Baixo , Melatonina/metabolismo , Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Idoso , Feminino , Expressão Gênica , Humanos , Hidrocortisona/metabolismo , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Proteínas Circadianas Period/genética , Proteínas Circadianas Period/metabolismo , Progesterona/metabolismoRESUMO
Timely production of glucocorticoid hormones in response to ACTH is essential for survival by coordinating energy intake and expenditure and acting as homeostatic regulators against stress. Adrenal cortisol response to ACTH is clock time dependent, suggesting that an intrinsic circadian oscillator in the adrenal cortex contributes to modulate the response to ACTH. Circadian clock gene expression has been reported in the adrenal cortex of several species. However, there are no reports accounting for potential involvement of adrenal clock proteins on cortisol response to ACTH. Here we explored whether the clock protein cryptochrome 2 (CRY2) knockdown modifies the adrenal response to ACTH in a primate. Adrenal gland explants from adult capuchin monkey (n = 5) were preincubated for 6 h with transfection vehicle (control) or with two different Cry2 antisense and sense probes followed by 48 h incubation in medium alone (no ACTH) or with 100 nm ACTH. Under control and sense conditions, ACTH increased cortisol production, whereas CRY2 suppression inhibited ACTH-stimulated cortisol production. Expression of the steroidogenic enzymes steroidogenic acute regulatory protein and 3beta-hydroxysteroid dehydrogenase at 48 h of incubation was increased by ACTH in control explants and suppressed by Cry2 knockdown. Additionally, we found that Cry2 knockdown decreased the expression of the clock gene brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein (Bmal1) at the mRNA and protein levels. Altogether these results strongly support that the clock protein CRY2 is involved in the mechanism by which ACTH increases the expression of steroidogenic acute regulatory protein and 3beta-hydroxysteroid dehydrogenase. Thus, adequate expression levels of components of the adrenal circadian clock are required for an appropriate cortisol response to ACTH.
Assuntos
Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/metabolismo , Hormônio Adrenocorticotrópico/farmacologia , Cebus/metabolismo , Flavoproteínas/metabolismo , Hidrocortisona/metabolismo , 3-Hidroxiesteroide Desidrogenases/metabolismo , Fatores de Transcrição ARNTL , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Ritmo Circadiano/fisiologia , Criptocromos , Flavoproteínas/genética , Modelos Animais , Fosfoproteínas/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais/fisiologiaRESUMO
The circadian production of glucocorticoids involves the concerted action of several factors that eventually allow an adequate adaptation to the environment. Circadian rhythms are controlled by the circadian timing system that comprises peripheral oscillators and a central rhythm generator located in the suprachiasmatic nucleus (SCN) of the hypothalamus, driven by the self-regulatory interaction of a set of proteins encoded by genes named clock genes. Here we describe the phase relationship between the SCN and adrenal gland for the expression of selected core clock transcripts (Per-2, Bmal-1) in the adult capuchin monkey, a New World, diurnal nonhuman primate. In the SCN we found a higher expression of Bmal-1 during the h of darkness (2000-0200 h) and Per-2 during daytime h (1400 h). The adrenal gland expressed clock genes in oscillatory fashion, with higher values for Bmal-1 during the day (1400-2000 h), whereas Per-2 was higher at nighttime (about 0200 h), resulting in a 9- to 12-h antiphase pattern. In the adrenal gland, the oscillation of clock genes was accompanied by rhythmic expression of a functional output, the steroidogenic enzyme 3beta-hydroxysteroid dehydrogenase. Furthermore, we show that adrenal explants maintained oscillatory expression of Per-2 and Bmal-1 for at least 36 h in culture. The acrophase of both transcripts, but not its overall expression along the incubation, was blunted by 100 nm melatonin. Altogether, these results demonstrate oscillation of clock genes in the SCN and adrenal gland of a diurnal primate and support an oscillation of clock genes in the adrenal gland that may be modulated by the neurohormone melatonin.
Assuntos
Glândulas Suprarrenais/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Ritmo Circadiano/fisiologia , Flavoproteínas/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Melatonina/farmacologia , Melatonina/fisiologia , Núcleo Supraquiasmático/metabolismo , 3-Hidroxiesteroide Desidrogenases/genética , Fatores de Transcrição ARNTL , Animais , Cebus , Criptocromos , RNA Mensageiro/análise , RNA Ribossômico 18S/análiseRESUMO
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.
Assuntos
Feto/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Melatonina/fisiologia , Transativadores/genética , Fatores de Transcrição ARNTL , Glândulas Suprarrenais/fisiologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Proteínas CLOCK , Cebus , Ritmo Circadiano/genética , Ritmo Circadiano/fisiologia , DNA Complementar/biossíntese , DNA Complementar/genética , Sulfato de Desidroepiandrosterona/sangue , Feminino , Hidrocortisona/sangue , Proteínas Nucleares/genética , Gravidez , Receptor MT1 de Melatonina/biossíntese , Receptor MT1 de Melatonina/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Núcleo Supraquiasmático/fisiologia , Temperatura , Fatores de Transcrição/genéticaRESUMO
The time of food availability induces important behavioral and metabolic adaptations. Animals subjected to feeding restricted to a few daytime hours show increased locomotor activity and body temperature in anticipation of mealtime. In addition, animals under ad libitum feeding show a marked postprandial raise in body temperature and in thermogenesis. The areas of the brain commanding these responses to food are partially known. We investigated in the rat the role of the infralimbic area, located in the medial prefrontal cortex, and considered a visceral-autonomic motor area, in the responses to ad libitum or restricted feeding schedule. We performed infralimbic cortex excitotoxic lesions using injections of ibotenic acid, and measured body temperature and locomotor activity by telemetry in rats under ad libitum and restricted feeding conditions. We found that bilateral infralimbic area lesions prevented both the anticipatory and the postprandial increases in core temperature, decreased mean temperature by nearly 0.3 degrees C during both light/dark phases, and increased daily temperature variability. In contrast, the lesion caused a rapid induction of the anticipatory locomotor activity. These results show that behavioral and metabolic responses to the time of food availability are commanded separately and that the infralimbic area is a key structure to adjust the body temperature to an upcoming meal.
Assuntos
Temperatura Corporal/fisiologia , Comportamento Alimentar/fisiologia , Sistema Límbico/fisiologia , Atividade Motora/fisiologia , Animais , Ritmo Circadiano , Agonistas de Aminoácidos Excitatórios/farmacologia , Ácido Ibotênico/farmacologia , Sistema Límbico/lesões , Masculino , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
Arousal depends on the concerted activity of the ascending arousal system (AAS) but specific stimuli may primarily activate some nuclei of this system. Motivated behaviours are characterized by behavioural arousal, although it is not known which AAS nuclei are active during a motivated behaviour. To address this issue, rats were rendered motivated for food by fasting them for 1 day and then were enticed with food that they could not obtain for varying periods of time. We studied the level of arousal by polysomnography or radiotelemetry, and Fos-ir in the AAS, during food enticing. We found a strong arousal and an early increase in Fos-ir in the histaminergic neurons from the tuberomammillary nucleus, after 30 min of enticing, followed by increased Fos-ir in the whole AAS if food enticing was prolonged to 1 or 2 hours. In contrast, food presentation to non-motivated rats did not increase arousal or Fos-ir in the tuberomammillary nucleus. As opposed to the active arousal of the motivated rats, passive arousal induced by sensory stimulation was associated with increased Fos-ir in the locus coeruleus and the orexin neurons, but not with increased Fos-ir in the tuberomammillary nucleus or in the other nuclei of the AAS. We conclude that the arousal during feeding-related motivated behaviour is associated primarily with the activation of the tuberomammillary nucleus, while the other arousal-related nuclei become active later on.
Assuntos
Nível de Alerta/fisiologia , Comportamento Alimentar/fisiologia , Regulação da Expressão Gênica/fisiologia , Histamina/metabolismo , Motivação , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Vias Aferentes/citologia , Vias Aferentes/metabolismo , Animais , Comportamento Animal , Temperatura Corporal/fisiologia , Contagem de Células/métodos , Alimentos , Hipotálamo/citologia , Hipotálamo/metabolismo , Imuno-Histoquímica/métodos , Masculino , Atividade Motora/fisiologia , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
BACKGROUND: Fully breastfeeding women experience an amenorrhoea of variable duration. Our aim was to identify in pregnancy, endocrine markers that could predict the duration of subsequent lactational amenorrhoea. METHODS: We studied 17 healthy women at 34 and 38 weeks gestation, and 1 and 3 months post-partum. The women fully breastfed until 6 months post-partum. During pregnancy, prolactin (PRL), oestrogens (total oestradiol, unconjugated oestrone, unconjugated oestriol), sex hormone binding globulin (SHBG), dehydroepiandrosterone sulphate (DHEA-S), progesterone and placental lactogen, and during post-partum PRL, oestrogens and SHBG, were measured. Free oestradiol in pregnancy and post-partum was calculated. RESULTS: Ten women experienced long (>6 months) and seven experienced short (<6 months) lactational amenorrhoea. At 38 weeks gestation, the women who experienced a long lactational amenorrhoea had twice as much PRL, about half the total oestradiol, lower SHBG concentration (P < 0.05, Student's t-test, Bonferroni modification) and similar free oestradiol concentration, compared with those who experienced short lactational amenorrhoea. The difference in PRL concentration persisted in post-partum postsuckling samples. CONCLUSION: At 38 weeks gestation, the ratio PRL/oestradiol identified all individual women according to the subsequent duration of their lactational amenorrhoea, suggesting that duration of lactational amenorrhoea is conditioned during pregnancy.
Assuntos
Amenorreia , Estradiol/sangue , Idade Gestacional , Período Pós-Parto , Prolactina/sangue , Adulto , Sulfato de Desidroepiandrosterona/sangue , Estriol/sangue , Estrona/sangue , Feminino , Humanos , Lactogênio Placentário/sangue , Gravidez , Progesterona/sangue , Globulina de Ligação a Hormônio Sexual/análise , Fatores de TempoRESUMO
OBJECTIVES: Indirect evidence suggests that adrenal steroid production in the human fetus may have a circadian rhythm. To assess whether there is a 24-hour rhythm of fetal cortisol in the human fetus, we investigated the relationship between fetal and maternal cortisol and cortisone concentrations in maternal, umbilical arterial, and umbilical venous blood samples over a 24-hour period. STUDY DESIGN: Elective cesarean sections were scheduled every 2 hours around the clock in 57 term (38-41 weeks' gestation) nonlaboring pregnant women. Plasma cortisol and cortisone concentrations were measured by high-pressure liquid chromatography. RESULTS: The mean 24-hour cortisol concentration was higher in umbilical arterial than in umbilical venous blood samples, 63.6 +/- 4.6 ng/mL (SEM) versus 48.7 +/- 3.2 ng/mL, respectively (P <.05). Fetal plasma cortisol showed a rhythm in the umbilical artery (acme from noon to 4 PM ) (1-way analysis of variance and least significant difference test; P <.05) but not in the umbilical vein. Umbilical arteriovenous differences showed no net transfer of cortisol to the fetus at any time of the day and net fetal production of cortisol from 8 AM to 6 PM. There was limited transfer of cortisone to the fetus and only in the 2 AM -to-noon time interval. CONCLUSION: These data suggest the presence of a 24-hour rhythm of fetal adrenal cortisol secretion that may be controlled by a fetal circadian pacemaker.
Assuntos
Ritmo Circadiano , Parto Obstétrico , Sangue Fetal , Hidrocortisona/sangue , Adulto , Cromatografia Líquida de Alta Pressão , Cortisona/sangue , Feminino , Humanos , GravidezRESUMO
The circadian time-keeping system is the neural system that allows predictive adaptation of individuals to the reproducible 24-hour day/night alternations of our planet. A biological clock, the suprachiasmatic nucleus, receives environmental information and imposes a circadian pattern to physiological functions. Since the suprachiasmatic nucleus develops early in gestation and circadian rhythms are present in the fetus and newborn, the circadian system seems to be functional in fetal life and can receive circadian inputs through the mother. The neonate moves to an environment in which the main time giving signal is the light:dark cycle. Teleologically, a term newborn should be fit to face this challenge. But this may be quite different for a preterm infant that trades the circadian environment to which it was previously exposed for the timeless environment of the Neonatal Intensive Care Nursery. Scientists and physicians should seek new experimental and clinical approaches to answer the challenging questions of perinatal chronomedicine.
Assuntos
Ritmo Circadiano , Feto/fisiologia , Recém-Nascido/fisiologia , Animais , Dopamina/fisiologia , Feminino , Humanos , Melatonina/fisiologia , Gravidez , Núcleo Supraquiasmático/embriologia , Núcleo Supraquiasmático/crescimento & desenvolvimentoRESUMO
We used FOS-immunoreactivity to map changes in the neuronal activity of brain nuclei related to the state of arousal, in rats under a restricted feeding schedule. Our main finding was the outstanding activation of the tuberomammillary nucleus 24h after a meal, and its steep deactivation, which was independent of actually having the meal. The time course of FOS activation and deactivation indicated a burst of tuberomammilary nucleus activity in close temporal relation with the increased locomotor activity shown by rats in anticipation of the next meal.
Assuntos
Métodos de Alimentação , Região Hipotalâmica Lateral/fisiologia , Animais , Nível de Alerta/fisiologia , Ritmo Circadiano/fisiologia , Comportamento Alimentar/fisiologia , Região Hipotalâmica Lateral/enzimologia , Imuno-Histoquímica , Masculino , Atividade Motora/fisiologia , Proteínas Serina-Treonina Quinases/análise , Ratos , Ratos Sprague-Dawley , Proteínas Quinases S6 Ribossômicas 90-kDaRESUMO
In the present paper, we have studied the impact of lactation upon fertility in the capuchin monkey, Cebus apella, under laboratory conditions. Nursing females (ten females, 12 postpartum periods) presented lactational amenorrhea (first menses at 159.2 +/- 9.0 vs 42.6 +/- 5.8 days postpartum in five non-nursing females, seven postpartum periods). Plasma estradiol and progesterone concentrations during lactational amenorrhea were lower than those during the follicular phase of the menstrual cycle. Prolactin was higher than in non-nursing females at 31-60 days postpartum. Interbirth interval, studied in three non-nursing (four intervals) and six nursing females (eight intervals) lasted for 349.5 +/- 11.8 and 613.4 +/- 30.8 days, respectively. In non-nursing females, early recovery of the menstrual cycle was followed by a residual infertility (mating but no pregnancy) lasting 152.8 +/- 7.9 days. In nursing females, recovery of the menstrual cycle was followed by an extended residual infertility of 301.5 +/- 22.7 days. Thus, in the capuchin monkey, nursing prolongs the interbirth interval by inducing lactational amenorrhea and extending the residual infertility period.
Assuntos
Cebus/fisiologia , Fertilidade , Lactação , Ciclo Menstrual/fisiologia , Amenorreia , Animais , FemininoRESUMO
To assess whether plasma prolactin (PRL) characteristics relate to lactogenesis and absence or presence of menstrual cycles, we measured bioactive PRL (BIO-PRL) using the Nb2 assay, immunoreactive PRL (IR-PRL) by radio-immunoassay, calculated equations describing the BIO-PRL-IR-PRL relationship and separated charged PRL isoforms (by chromatofocusing) in five amenorrhoeic and five cycling nursing women at 6 months postpartum and in 10 cycling non-nursing women. Plasma samples were drawn before and 30 min after a suckling episode at 0800, 1600 and 2400 h in nursing women and at the same hours in non-nursing women. BIO-PRL and IR-PRL concentrations were highest in amenorrhoeic nursing women, intermediate in cycling nursing women and lowest in cycling non-nursing women. The BIO-PRL-IR-PRL relationship shows that a given amount of IR-PRL corresponds to equivalent amounts of BIO-PRL in cycling nursing and cycling non-nursing women, and to a larger extent in amenorrhoeic nursing women. IR-PRL was present in plasma as several charge isoforms. Bioactive isoforms eluting at pH 6.0-5.1 were found in amenorrhoeic and cycling nursing women, reaching similar concentrations after suckling. Bioactive isoforms eluting at pH 7.0-6.1 were found only in amenorrhoeic nursing women. We speculate that isoforms eluting at pH 6.0-5.1 may play a role in lactation and isoforms eluting at pH 7.0-6.1, in lactational amenorrhoea.
Assuntos
Lactação/fisiologia , Prolactina/fisiologia , Adulto , Aleitamento Materno , Feminino , Humanos , Ciclo Menstrual/fisiologia , Isoformas de Proteínas/fisiologiaRESUMO
Penetration of light into the pregnant sheep uterus was studied in 9 ewes, gestational ages 40 to 142 days (term 147 days). Light sensors were placed inside the pregnant horn and over the flank skin overlying the position of the uterine horn. To perform the experiments, the ewes were placed in a study cage outdoors and light sensors were connected to a luxometer. Simultaneous measurements were obtained from the intrauterine and the external sensors in the shade at noon. The amount of light detected inside the uterus increased with gestational age from two lux at 40 days to 51.1 +/- 16.5 (n = 5) lux at 142 days (0.2 and 5.4% of the amount of light detected at the maternal flank). Measurements through the 24 h were done in four pregnant ewes at 142 days gestation under natural photoperiod (13.5 light:10.5 dark). In these experiments, the intensity of intrauterine light changed through the 24 h, reflecting the changes in the intensity of the sunlight. Maximal intrauterine light values were observed at noon, corresponding to 4.7% of incident light. Small but detectable values were observed at 0900 and 1800 h. Our data show that, at mid gestation, light reaches the pregnant uterus and that, at late gestation, changes in intrauterine lighting throughout the 24 h are present reflecting the changes in external daylight. Therefore the sheep fetus is exposed to light-dark transitions at dawn and dusk, and to a peak of light at midday.
Assuntos
Ritmo Circadiano , Luz , Ovinos , Útero , Animais , Feminino , Idade Gestacional , Fotoperíodo , GravidezRESUMO
BACKGROUND: Maternal smoking negatively affects birth weight, breast milk volume and growth at one month of age. AIM: To study the effect of maternal smoking on the growth of three month old infants. SUBJECTS AND METHODS: Ten smoking and 10 non smoking mothers with one month old children, under exclusive breast feeding, were selected for the study. Urinary cotinine levels in the mothers and children were measured to assess smoking. Two months later, children were reassessed. RESULTS: Smoking mothers consumed a mean of 6.5 cigarettes/day. Compared to non smokers, urinary cotinine levels were higher in these mothers (60 +/- 21 and 1428 +/- 716 ng/ml respectively, p < 0.001) and their offspring (21 +/- 20 and 156 +/- 101 ng/ml respectively p < 0.001). Compared with smokers, at three months of age, children of non smoking mothers had a higher average weight (5829 +/- 498 and 6325 +/- 427 g, p < 0.02). CONCLUSIONS: Measurement of urinary cotinine levels is a reliable and objective measure of maternal smoking and nicotine transfer to the offspring. It also allows the assessment of passive smoking. Maternal smoking adversely affects child growth at three months of age.
Assuntos
Crescimento/efeitos dos fármacos , Comportamento Materno , Fumar/efeitos adversos , Adulto , Peso ao Nascer , Estatura , Cotinina/urina , Feminino , Humanos , Lactente , Recém-NascidoRESUMO
Capuchin monkey (Cebus apella) is a new world primate that in recent years has become important in biomedical research. The purpose of this study was to establish and correlate normal fetal growth parameters with gestational age in capuchin monkeys. In seven pregnant animals serial ultrasonic assessment of gestational sac (GS), embryo/fetal greatest length (GL), biparietal diameter (BPD), thorax height (TH), and femur length (FL) were performed. Identification of the GS was possible on day 23+/-2.8 (X +/- SE). The embryo and its heartbeat was detected on day 32.7+/-2.8, the GL being measurable thereafter. By day 45.4+/-1.4 BPD and TH were measurable. FL could only be measured from day 70.6+/-2.1. Predictive regression equations of gestational age (GA) were modeled with data obtained. In addition, preliminary data of fetal heart rate showed a decrease in frequency with advancing gestation.
Assuntos
Cebus/embriologia , Desenvolvimento Embrionário e Fetal , Ultrassonografia Pré-Natal/veterinária , Animais , Composição Corporal , Feminino , Idade Gestacional , Frequência Cardíaca Fetal , GravidezRESUMO
To assess whether the duration of lactational amenorrhoea can be predicted in individual women, we studied the pre- and post-suckling concentrations of immune prolactin (IR-PRL) and of bioactive prolactin (BIO-PRL) and basal concentrations of oestradiol in ten amenorrhoeic fully nursing women at 3 months post-partum. The women were of similar age, weight and had infants of similar growth rate. Five of these women were to experience long amenorrhoea (>180 days) and the others short amenorrhoea (<180 days). Blood samples were drawn 30 min after a suckling episode initiated at 0800 h, 1600 h and 2400 h. BIO-PRL distinguished between groups of women at 0030 h but not at other times, while there was considerable overlap between values for IR-PRL and oestradiol at all times studied. At 1630 h, the ratios post-suckling BIO-PRL: oestradiol and post-suckling IR-PRL:oestradiol were above 2000 in the women that were to experience long amenorrhoea and below this threshold in the other women. The ratio post-suckling BIO-PRL:oestradiol provided more information since the difference between the lowest ratio in the long amenorrhoea and the highest ratio in the short was 699, while it was 520 for the IR-PRL:oestradiol ratio. The determination of these ratios may help to predict the duration of lactational amenorrhoea in individual fully nursing women.