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Biomedical subjects

M Serón-Ferré

Publications and source records attributed to M Serón-Ferré.

At least 19 recordsLinked to original sources

Differential effects of infralimbic cortical lesions on temperature and locomotor activity responses to feeding in rats.

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.

Animals↗

Arousal and differential Fos expression in histaminergic neurons of the ascending arousal system during a feeding-related motivated behaviour.

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.

Afferent Pathways↗

The development of circadian rhythms in the fetus and neonate.

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.

Animals↗

Twenty-four-hour pattern of cortisol in the human fetus at term.

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.

Adult↗

Plasma prolactin/oestradiol ratio at 38 weeks gestation predicts the duration of lactational amenorrhoea.

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.

Adult↗

Impact of lactation upon fertility in the New World primate capuchin monkey (Cebus apella).

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.

Amenorrhea↗

Bioactivity of prolactin isoforms: lactation and recovery of menses in nursing women.

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.

Adult↗

Diurnal changes in light intensity inside the pregnant uterus in sheep.

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.

Animals↗

Study of prenatal growth in the capuchin monkey (Cebus apella) by ultrasound.

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.

Animals↗

[Effect of maternal smoking on offspring growth].

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.

Adult↗

Post-suckling prolactin:oestradiol ratio--a potential index to predict the duration of lactational amenorrhoea in women.

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.

Adult↗

Development of a radioimmunoassay for Cebus apella prolactin.

Prolactin (PRL) is a pituitary hormone that plays important roles in mammalian reproductive physiology, specially lactation. The regulation of PRL secretion shows important species differences. To study PRL regulation in a subhuman primate, the Cebus apella, we developed an heterologous radioimmunoassay using an antibody against rhesus PRL (anti-m5PRL) and a Cebus apella pituitary extract as PRL standard. The assay has a sensitivity that allows measurements of cebus PRL in small amounts of Cebus apella plasma obtained from animals in different physiological conditions. Plasma cebus PRL concentrations (+/-SEM) varied in different reproductive stages. PRL concentration in adult Cebus apella females that have regular menstrual cycles (161.6 +/- 15.0 mIU/ml) was similar to that found in adult (100.3 +/- 7.6 mIU/ml) and prepuberal males (101.2 +/- 3.9 mIU/ml). PRL concentration was higher in pregnant (677.8 +/- 11.8 mIU/ml) and in nursing (625.0 +/- 47.0 mIU/ml) Cebus apella females than in 15-d post-partum non-nursing (369.0 +/- 19.0 mIU/ml) and cycling females. PRL concentration in Cebus apella newborns (719.0 +/- 49.2 mIU/ ml) was similar to that found in pregnant and nursing females, and higher than in the other females as well as adult and prepuberal males. These differences in PRL concentration in different physiological conditions are similar to that observed in humans and other primates. A PRL response to thyrotropin releasing hormone (TRH) was demonstrated in 2 nursing Cebus apella females, similar to the response found in nursing woman and rhesus. Altogether, the data presented support the proposal that the assay developed to measure PRL in Cebus apella is an adequate tool to study the physiology of PRL in this species.

Animals↗

Effect of constant light on fetal and maternal prolactin rhythms in sheep.

A 24-h rhythm of plasma PRL is present in fetal sheep. This rhythm is synchronized to an environmental clue (zeitgeber). We determined whether the light-dark cycle (L:D) is a zeitgeber for the fetal PRL rhythm and, if so, whether the mother might convey this zeitgeber to the fetus. We kept nine ewes (twin pregnancies) in constant light (L:L) and five ewes (singleton) in 14:10 L:D from 110 days gestation. Fetuses and mothers were catheterized at 119 days gestation. Blood samples were taken hourly for 24 h after 16 days under L:L or L:D. A mean 24-h rhythm of PRL was found (by RIA) in fetuses under L:D, but not in those under L:L. However, fetuses under L:L showed individual 24-h PRL rhythms (cosinor analysis) whose acrophases were distributed around the clock. Nonsynchronized rhythms persisted after 23 and 30 days of L:L. Acrophases of PRL rhythms within a set of twins were closer than those between sets, suggesting that twins were responding to a common signal. These findings indicate that the L:D cycle is a zeitgeber for the PRL rhythm in fetal sheep and suggest that the mother might convey the zeitgeber.

Animals↗

Day-night changes in c-fos expression in the fetal sheep suprachiasmatic nucleus at late gestation.

The suprachiasmatic nucleus (SCN) is a circadian oscillator in mammals and shows day-night changes in metabolic activity. To investigate whether the fetal sheep SCN behaves as a circadian oscillator, day-night changes in c-fos expression, a marker of neuronal activity, were measured. Eight fetal sheep were sacrificed at 135 days gestation--four at day-time (1200 hours) and four at night-time (2400 hours). Fetal brains were fixed, removed and cut in 40-microns serial coronal sections. Alternate sections were incubated with anti-Fos antibody (1:500) and Fos expression was revealed with extra-avidin-peroxidase and 3,3'-diaminobenzidine or stained with cresyl violet. The number of Fos-immunoreactive (Fos-ir) neurons per mm2 in the rostral, intermediate and caudal regions of the fetal sheep SCN was counted. Fetuses sacrificed in the day-time showed a higher number of Fos-ir neurons per mm2 (mean +/- s.e.; 516.7 +/- 60.1) in the three regions of the SCN than fetuses sacrificed at night-time (140.5 +/- 21.8). In addition, at night-time Fos-ir neurons were mainly localized to the ventrolateral area of the SCN. These findings demonstrate day-night changes in molecular activity consistent with the presence of a circadian oscillator in the fetal sheep SCN.

Animals↗

Diminished luteinizing hormone biopotency in breastfeeding women.

The effect of nursing on plasma luteinizing hormone bioactivity (B-LH) and immunoactivity (I-LH) was assessed at 4 and 6 months post partum in fully nursing women who experienced their first bleeding between months 5 and 6 post partum (n = 6, short amenorrhoea) or after the month 6 (n = 10, long amenorrhoea). Controls were 10 non-nursing fertile women. Blood samples were drawn twice weekly at month 4 post partum and at month 6 post partum. In the nursing women who were cycling at month 6 and in non-nursing women samples were drawn during the follicular phase. I-LH was measured by a time resolved immunofluorometric assay (DELFIA) and B-LH by the mouse Leydig cell assay. Nursing decreased B-LH more than I-LH resulting in a relationship between B-LH and I-LH different to that of non-nursing women (B-LH = 2.84 x I-LH-0.16 and B-LH = 4.27 x I-LH + 3.11 respectively, P < 0.05, by likelihood test). Plasma B-LH or I-LH were similar in nursing women with short or long amenorrhoea. In conclusion, nursing alters the quality of circulating LH, however, the decreased LH steroidogenic potency does not play a role in determining the duration of lactational amenorrhoea.

Adult↗

Luteinizing hormone pulsatile release and the length of lactational amenorrhoea.

The pattern of luteinizing hormone (LH) pulsatile release and the mean concentrations of follicle-stimulating hormone, oestradiol and progesterone were studied in nursing and non-nursing women. Blood samples were drawn at 5 min intervals between 10:00 and 14:00 h and between 22:00 and 02:00 h at months 3-4, 5-6, 7-8 and 9-10 postpartum in nursing women and in the follicular phase in non-nursing women. In nursing women, mean LH concentrations at months 3-4 were significantly lower than in non-nursing cycling women only in the subgroup which subsequently experienced > 6 months of lactational amenorrhoea, although all were fully nursing with a similar suckling frequency. LH pulses in plasma were found at all times in nursing women. There were no significant differences in the frequency (about four pulses every 4 h), amplitude or duration of LH pulses related to the duration of amenorrhoea, nor did these parameters vary significantly between amenorrhoeic or cycling nursing women and non-nursing women. Nursing amenorrhoeic women exhibited a normal frequency of LH pulse well in advance of the resumption of the first post-partum menses, suggesting that mechanisms other than the suppression of the gonadotrophin-releasing hormone pulse generator intervened in the inhibition of ovarian function during lactation.

Adult↗

Prolactin bioactivity and the duration of lactational amenorrhea.

In our population, only half of fully nursing women remain amenorrheic 6 months postpartum. The other half recover their menstrual cycles between 90-180 days postpartum in spite of a high suckling frequency and elevated immunoreactive PRL (IR-PRL) concentrations. To further investigate the association of PRL with the recovery of ovarian function, we compared PRL bioactivity (BIO-PRL) 3-4 months postpartum in fully nursing amenorrheic women who subsequently experienced long (> 180 days; n = 5) or short (< 180 days; n = 5) lactational amenorrhea. In the present study, BIO-PRL in plasma was measured by the Nb2 lymphoma cell assay in samples taken before and 30 min after a suckling episode at 0800, 1600 and 2400 h. Women in the long amenorrhea group had higher overall mean BIO-PRL (mean +/- SE, 129.9 +/- 12.1 micrograms/L) than nursing women in the short amenorrhea group (66.6 +/- 5.2 micrograms/L; P < 0.05). Mean basal values were similar, but the women in the long amenorrhea group had more BIO-PRL in response to suckling (160.1 +/- 4.0 vs. 71.9 +/- 6.7 micrograms/L; P < 0.05). Compared with their respective basal values, nursing women in the long amenorrhea group demonstrated increased BIO-PRL in response to suckling, whereas the other group did not. The relationships between BIO-PRL and IR-PRL were similar in the two groups of nursing women before suckling. However, after suckling, the long amenorrhea group had significantly higher BIO-PRL levels than IR-PRL levels (P < 0.05, by likelihood test) than the short amenorrhea group. This suggests that suckling differentially changes in each group either the composition of PRL present or substances that may modify the bioactivity of PRL in plasma.

Adult↗

Prenatal development of the retinohypothalamic pathway and the suprachiasmatic nucleus in the sheep.

Circadian rhythms are present during fetal life in several mammalian species. To characterize the ontogeny of the neural mechanisms that account for circadian rhythmicity in a precocious species, we studied the prenatal development of the retinohypothalamic pathway in lambs (gestation period of 147 days), using horseradish peroxidase and wheat germ agglutinin as anterograde tracers. The suprachiasmatic nucleus was present as early as embryonic day 52 (E52). After E58, the suprachiasmatic nucleus reached its full number of neurons, estimated by the disector method in about 160,000 cells per nucleus at E62. The retinohypothalamic axons invaded the suprachiasmatic nucleus from E58, while neuroblasts were still migrating to the nucleus. At E62, there was a strong retinal projection that evolved until E121, when the retinal afferents established their definitive pattern of distribution in the ventral and central regions of the suprachiasmatic nucleus, and adjacent hypothalamic structures. The development of the retinohypothalamic pathway was delayed by about a week relative to the innervation of other subcortical visual centers. The present findings demonstrated an early prenatal development of the visual pathways in lambs, including the retinohypothalamic pathway, suggesting that the mechanisms for the visual entrainment of circadian rhythms in lambs may be functioning several weeks before birth.

Animals↗