Endogenous circannual rhythm in LH secretion: insight from signal analysis coupled with mathematical modelling

In sheep as in many vertebrates, the seasonal pattern of reproduction is timed by the annual photoperiodic cycle, characterized by seasonal changes in the daylength. The photoperiodic information is translated into a circadian profile of melatonin secretion. After multiple neuronal relays (within the hypothalamus), melatonin impacts GnRH (gonadotrophin releasing hormone) secretion that in turn controls ovarian cyclicity. The pattern of GnRH secretion is mirrored into that of LH (luteinizing hormone) secretion, whose plasmatic level can be easily measured. We addressed the question of whether there exists an endogenous circannual rhythm in a tropical sheep population that exhibits clear seasonal ovarian activity when ewes are subjected to temperate latitudes. We based our analysis on LH time series collected in the course of 3 years from ewes subjected to a constant photoperiodic regime. Due to intra- and inter- animal variability and unequal sampling times, the existence of an endogenous rhythm is not straightforward. We have used time-frequency signal processing methods to extract hidden rhythms from the data. To further investigate the LF (low frequency) and HF (high frequency) components of the signals, we have designed a mathematical model of LH plasmatic level accounting for the effect of experimental sampling times. The model enables us to confirm the existence of an endogenous circannual rhythm, to investigate the action mechanism of photoperiod on the pulsatile pattern of LH secretion (control of the interpulse interval) and to conclude that the HF component is mainly due to the experimental sampling protocol

Genetic parameters of spontaneous spring ovulatory activity in Mérinos d'Arles sheep

The genetic parameters of spontaneous spring ovulatory activity were investigated in the Mérinos d’Arles breed under the usual pastoral and transhumant management conditions of this breed in southeastern France. Ovulatory activity was determined by assaying the plasma progesterone concentration in two blood samples taken 8-10 days apart. The data set consisted of 1 887 ovulatory activity performance measurements in 1995, 1996 and 1997 on 933 ewes, daughters of 176 rams. The effects of the ’physiological status’ (hoggets, adult ewes with or without lambing in the previous autumn), age and live weight just before the mating period were found to be highly significant. They were included in the linear animal model and the threshold sire model used to estimate genetic parameters. On average, 27.9 % of ewes exhibited ovulatory activity in April. Age and live weight just before the mating period had a marked positive effect on ovulatory activity. A difference of about 8-9 % was observed between extreme classes for these factors. The heritability and repeatability estimated through the linear model were 0.20 (standard error: 0.04) and 0.30 (0.07), respectively. When using the threshold model, the heritability was 0.37. These values led us to conclude that a genetic approach for improving spontaneous spring ovulatory activity should be further developed. Nevertheless, further studies are necessary to determine all the implications of such selection.Les paramètres génétiques de l’activité ovulatoire spontanée au printemps ont été estimés en race Mérinos d’Arles dans le système d’élevage pastoral traditionnel (transhumance estivale) du sud-est de la France. Le dosage de la progestérone plasmatique dans deux prélèvements sanguins effectués à 8-10 j d’intervalle a permis de déterminer l’activité ovulatoire des brebis. 1887 performances d’activité ovulatoire ont été enregistrées en 1995, 1996 et 1997, sur 933 brebis issues de 176 béliers. Le «statut physiologique » (antenaises, brebis adultes avec ou sans mise bas à l’automne précédent), l’âge et le poids au moment de la lutte des brebis ont des effets très significatifs sur l’activité ovulatoire. Ils ont été pris en compte dans le modèle animal linéaire et le modèle père à seuil utilisés pour estimer les paramètres génétiques. En moyenne, 27,9 % des brebis présentaient une activité ovulatoire en avril. L’âge et le poids au moment de la lutte ont un net effet positif sur l’activité ovulatoire. Une différence de 8-9 % a été observée entre les classes extrêmes pour ces facteurs. L’héritabilité et la répétabilité estimées avec le modèle linéaire sont de 0,20 (erreur standard : 0,04) et de 0,30 (0,07), respectivement. L’héritabilité calculée avec le modèle à seuil est de 0,37. En conclusion, compte tenu de ces valeurs, l’approche génétique visant à améliorer l’activité ovulatoire spontanée au printemps mérite d’être poursuivie. Néanmoins, d’autres études sont nécessaires pour connaître toutes les implications que supposent une telle sélection

GPR50 is the mammalian ortholog of Mel1c: Evidence of rapid evolution in mammals

<p>Abstract</p> <p>Background</p> <p>The melatonin receptor subfamily contains three members Mel1a, Mel1b and Mel1c, found in all vertebrates except for Mel1c which is found only in fish, Xenopus species and the chicken. Another receptor, the melatonin related receptor known as GPR50, found exclusively in mammals and later identified as a member of the melatonin receptor subfamily because of its identity to the three melatonin receptors despite its absence of affinity for melatonin. The aim of this study was to describe the evolutionary relationships between GPR50 and the three other members of the melatonin receptor subfamily.</p> <p>Results</p> <p>Using an <it>in silico </it>approach, we demonstrated that GPR50 is the ortholog of the high affinity Mel1c receptor. It was necessary to also study the synteny of this gene to reach this conclusion because classical mathematical models that estimate orthology and build phylogenetic trees were not sufficient. The receptor has been deeply remodelled through evolution by the mutation of numerous amino acids and by the addition of a long C-terminal tail. These alterations have modified its affinity for melatonin and probably affected its interactions with the other two known melatonin receptors MT1 and MT2 that are encoded by Mel1a and Mel1b genes respectively. Evolutionary studies provided evidence that the GPR50 group evolved under different selective pressure as compared to the orthologous groups Me11 a, b, and c.</p> <p>Conclusion</p> <p>This study demonstrated that there are only three members in the melatonin receptor subfamily with one of them (Me11c) undergoing rapid evolution from fishes and birds to mammals. Further studies are necessary to investigate the physiological roles of this receptor.</p

Genetic variability of the pattern of night melatonin blood levels in relation to coat changes development in rabbits

To assess the genetic variability in both the nocturnal increase pattern of melatonin concentration and photoresponsiveness in coat changes, an experiment on 422 Rex rabbits (from 23 males) raised under a constant light programme from birth was performed. The animals were sampled at 12 weeks of age, according to 4 periods over a year. Blood samples were taken 7 times during the dark phase and up to 1 h after the lighting began. Maturity of the fur was assessed at pelting. Heritability estimates of blood melatonin concentration (0.42, 0.17 and 0.11 at mid-night, 13 and 15 h after lights-out respectively) and strong genetic correlations between fur maturity and melatonin levels at the end of the dark phase (-0.64) indicates that (i) the variability of the nocturnal pattern of melatonin levels is under genetic control and (ii) the duration of the nocturnal melatonin increase is a genetic component of photoresponsiveness in coat changes

Identification of Melatonin-Regulated Genes in the Ovine Pituitary Pars Tuberalis, a Target Site for Seasonal Hormone Control

The pars tuberalis (PT) of the pituitary gland expresses a high density of melatonin (MEL) receptors and is believed to regulate seasonal physiology by decoding changes in nocturnal melatonin secretion. Circadian clock genes are known to be expressed in the PT in response to the decline (Per1) and onset (Cry1) of MEL secretion, but to date little is known of other molecular changes in this key MEL target site. To identify transcriptional pathways that may be involved in the diurnal and photoperiod-transduction mechanism, we performed a whole genome transcriptome analysis using PT RNA isolated from sheep culled at three time points over the 24-h cycle under either long or short photoperiods. Our results reveal 153 transcripts where expression differs between photoperiods at the light-dark transition and 54 transcripts where expression level was more globally altered by photoperiod (all time points combined). Cry1 induction at night was associated with up-regulation of genes coding for NeuroD1 (neurogenic differentiation factor 1), Pbef / Nampt (nicotinamide phosphoribosyltransferase) , Hif1α (hypoxia-inducible factor-1α), and Kcnq5 (K channel) and down-regulation of Rorβ, a key clock gene regulator. Using in situ hybridization, we confirmed day-night differences in expression for Pbef / Nampt, NeuroD1, and Rorβ in the PT. Treatment of sheep with MEL increased PT expression for Cry1, Pbef / Nampt, NeuroD1, and Hif1α, but not Kcnq5. Our data thus reveal a cluster of Cry1-associated genes that are acutely responsive to MEL and novel transcriptional pathways involved in MEL action in the PT

Turnover rate of cerebrospinal fluid in female sheep: changes related to different light-dark cycles

<p>Abstract</p> <p>Background</p> <p>Sheep are seasonal breeders. The key factor governing seasonal changes in the reproductive activity of the ewe is increased negative feedback of estradiol at the level of the hypothalamus under long-day conditions. It has previously been demonstrated that when gonadotropin secretions are inhibited during long days, there is a higher concentration of estradiol in the cerebrospinal fluid (CSF) than during short days. This suggests an involvement of the CSF and choroid plexus in the neuroendocrine regulatory loop, but the mechanisms underlying this phenomenon remain unknown. One possible explanation of this difference in hormonal content is an effect of concentration or dilution caused by variations in CSF secretion rate. The aim of this study was thus to investigate changes in the CSF turnover rate related to light-dark cycles.</p> <p>Methods</p> <p>The turnover rate of the CSF was estimated by measuring the time taken for the recovery of intraventricular pressure (IVP) after removal of a moderate volume (0.5 to 2 ml) of CSF (slope in mmHg/min). The turnover rate was estimated three times in the same group of sheep: during a natural period of decreasing day-length corresponding to the initial period when gonadotropin activity is stimulated (SG1), during a long-day inhibitory period (IG), and finally during a short-day stimulatory period (SG2).</p> <p>Results</p> <p>The time taken and the speed of recovery of initial IVP differed between groups: 8 min 30 sec, 0.63 ± 0.07 mmHg/min(SG1), 11 min 1 sec, 0.38 ± 0.06 mmHg/min (IG) and 9 min 0 sec, 0.72 ± 0.15 mmHg/min (SG2). Time changes of IVP differed between groups (ANOVA, p < 0.005, SG1 different from IG, <it>p </it>< 0.05). The turnover rate in SG2: 183.16 ± 23.82 μl/min was not significantly different from SG1: 169. 23 ± 51.58 μl/min (Mann-Whitney test, <it>p </it>= 0.41), but was significantly different from IG: 71.33 ± 16.59 μl/min (<it>p </it>= 0.016).</p> <p>Conclusion</p> <p>This study shows that the turnover rate of CSF in ewes changes according to the light-dark cycle; it is increased during short day periods and reduced in long day periods. This phenomenon could account for differences in hormonal concentrations in the CSF in this seasonal species.</p

Cycle annuel de reproduction chez la brebis : signaux photoperiodiques et rythme endogene

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Rythmes saisonniers de reproduction

National audienc

Neuroendocrine basis of seasonal reproduction in sheep and goats

International audienc