The major limitation to the development of embryo production in cattle is the strong between-animal variability in ovulatory response to FSH-induced superovulation, mainly due to differences in ovarian activity at the time of treatment. This study aimed to establish whether anti-Müllerian hormone (AMH) was an endocrine marker of follicular populations in the cow, as in human, and a possible predictor of the ovarian response to superovulation. Anti-Müllerian hormone concentrations in plasma varied 10-fold between cows before treatment and were found to be highly correlated with the numbers of 3- to 7-mm antral follicles detected by ovarian ultrasonography before treatment (r=0.79, P<0.001) and the numbers of ovulations after treatment (r=0.64, P<0.01). Between-animal differences in AMH concentrations were found to be unchanged after a 3-mo delay (r=0.87, P<0.01), indicating that AMH endocrine levels were characteristic of each animal on a long-term period. The population of healthy 3- to 7-mm follicles was the main target of superovulatory treatments, contained the highest AMH concentrations and AMH mRNA levels compared with larger follicles, and contributed importantly to AMH endocrine levels. In conclusion, AMH was found to be a reliable endocrine marker of the population of small antral gonadotropin-responsive follicles in the cow. Moreover, AMH concentrations in the plasma of individuals were indicative of their ability to respond to superovulatory treatments.

Anti-Müllerian hormone (AMH) is an endocrine marker that can help predict superovulatory responses to treatments administered to cows for embryo production. However, the optimal time of the estrous cycle at which a blood test should be performed for a highly reliable prognosis has not yet been established. Moreover, little is known about the regulation of AMH production. To answer these questions, a study was designed to investigate the regulation of AMH production in cows selected for their high or low ovulatory responses to superovulation. At the granulosa cell level, AMH production was inhibited by follicle-stimulating hormone but enhanced by bone morphogenetic proteins. At the follicular level, the expression of AMH within the follicle was dependent on the stage of follicular development. At the ovarian level, the size of the pool of small antral growing follicles determined ovarian AMH production. At the endocrine level, AMH followed a specific dynamic profile during the estrous cycle, which occurred independently of the follicular waves of terminal follicular development. Cows selected for their high or low responses to superovulation did not differ in the regulation of AMH production, but cows with higher responses had higher plasma AMH concentrations throughout the cycle. The optimal period of the estrous cycle at which to measure AMH concentrations with the aim of selecting the best cows for embryo production was found to be at estrus and after Day 12 of the cycle. Based on this multiscale study, we propose a model that integrates the different regulatory levels of AMH production.

The growing follicles develop from a reserve of primordial follicles constituted early in life. From this pre-established reserve, a second ovarian reserve is formed, which consists of gonadotropin-responsive small antral growing follicles and is a dynamic reserve for ovulation. Its size, evaluated by direct antral follicular count or endocrine markers, determines the success of assisted reproductive technologies in humans and embryo production biotechnologies in animals. Strong evidence indicates that these two reserves are functionally related. The size of both reserves appears to be highly variable between individuals of similar age, but the equilibrium size of the dynamic reserve in adults seems to be specific to each individual. The dynamics of both follicular reserves appears to result from the fine tuning of regulations involving two main pathways, the phosphatase and tensin homolog (PTEN)/phosphatidylinositol-3 kinase (PI3K)/3-phosphoinositide-dependent protein kinase-1 (PDPK1)/v-akt murine thymoma viral oncogene homolog 1 (AKT1) and the bone morphogenetic protein (BMP)/anti-Müllerian hormone (AMH)/SMAD signaling pathways. Mutations in genes encoding the ligands, receptors, or signaling effectors of these pathways can accelerate or modulate the exhaustion rate of the ovarian reserves, causing premature ovarian insufficiency (POI) or increase in reproductive longevity, respectively. With female aging, the decline in primordial follicle numbers parallels the decrease in the size of the dynamic reserve of small antral follicles and the deterioration of oocyte quality. Recent progress in our knowledge of signaling pathways and their environmental and hormonal control during adult and fetal life opens new perspectives to improve the management of the ovarian reserves.

Models of the electro-mechanical activity of the cardiac muscle can be very useful in computing stress, strain and action potential fields from three-dimensional image processing. We designed a chemically-controlled constitutive law of cardiac myofibre mechanics, acting on the mesoscopic scale and devoted to be embedded into a macroscopic model. This law ensues from the modelling of the collective behaviour of actin-myosin molecular motors, acting on the nanoscopic scale to convert chemical into mechanical energy. The resulting dynamics of sarcomeres, acting on the microscopic scale, is shown to be consistent with the "sliding filament hypothesis", which was first introduced by A. F. Huxley [1]. Excitation-Contraction Model on the Myofibre ScaleThe contractile elements (CE) of myofibres are able to produce stress while shortening in response to a chemical input u(t), mainly depending on the calcium concentration. We propose, as a constitutive relation in the myofibre direction between stress σ and strain ε, the following set of controlled differential equations (modified from [2], [3]) of visco-elasto-plastic type:The system is able to account for : shortening from resting conditions (ε = 0) in response to u(t), passive behaviour of CE (u = 0) as described in [4], static relation between ε and σ, and isotonic contraction (σ c = 0 andε < 0) as in Hill's experimental model. For the purpose of ultrasonographic-image processing, the system is further being embedded into a partial differential equation model including reaction-diffusion equations to rule the propagation of action potential. Excitation-Contraction Model on the Sarcomere ScaleOn a microscopic scale, the sarcomere is made up of thin and thick parallel filaments. When ATP is available and the intracellular level of calcium reaches a threshold, myosin heads of the thick filament become likely to bind actin sites on the thin filament. The elastic free energy W of the actin-myosin interaction is responsible for muscle contraction: stress response to strain causes relative sliding of the actin over the myosin filament. Let n(ξ, t) be the density of crossbridges with strain ξ at time t and ε the strain (normalized by the ratio of rest to maximal length of cross-bridges). Then, Huxley's model is:W. Niessen and M.

The molecular mechanisms and hidden dynamics governing ERK activation by the angiotensin II type 1A receptor are studied and deciphered, revealing a signal balancing mechanism that is found to be relevant to a range of other seven transmembrane receptors.

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The endocrine control of the reproductive function is often studied from the analysis of luteinizing hormone (LH) pulsatile secretion by the pituitary gland. Whereas measurements in the cavernous sinus cumulate anatomical and technical difficulties, LH levels can be easily assessed from jugular blood. However, plasma levels result from a convolution process due to clearance effects when LH enters the general circulation. Simultaneous measurements comparing LH levels in the cavernous sinus and jugular blood have revealed clear differences in the pulse shape, the amplitude and the baseline. Besides, experimental sampling occurs at a relatively low frequency (typically every 10 min) with respect to LH highest frequency release (one pulse per hour) and the resulting LH measurements are noised by both experimental and assay errors. As a result, the pattern of plasma LH may be not so clearly pulsatile. Yet, reliable information on the InterPulse Intervals (IPI) is a prerequisite to study precisely the steroid feedback exerted on the pituitary level. Hence, there is a real need for robust IPI detection algorithms. In this article, we present an algorithm for the monitoring of LH pulse frequency, basing ourselves both on the available endocrinological knowledge on LH pulse (shape and duration with respect to the frequency regime) and synthetic LH data generated by a simple model. We make use of synthetic data to make clear some basic notions underlying our algorithmic choices. We focus on explaining how the process of sampling affects drastically the original pattern of secretion, and especially the amplitude of the detectable pulses. We then describe the algorithm in details and perform it on different sets of both synthetic and experimental LH time series. We further comment on how to diagnose possible outliers from the series of IPIs which is the main output of the algorithm.

Le manuscrit disponible sur cette page "Clement_Vidal.ps" est une version pré-printWe investigate a model of the GnRH pulse and surge generator, with the definite aim of constraining the model GnRH output with respect to a physiologically relevant list of specifications. The alternating pulse and surge pattern of secretion results from the interaction between a GnRH secreting system and a regulating system exhibiting fast-slow dynamics. The mechanisms underlying the behavior ofInternational audienceWe investigate a model of the GnRH pulse and surge generator, with the definite aim of constraining the model GnRH output with respect to a physiologically relevant list of specifications. The alternating pulse and surge pattern of secretion results from the interaction between a GnRH secreting system and a regulating system exhibiting fast-slow dynamics. The mechanisms underlying the behavior of the model are reminded from the study of the Boundary-Layer System according to the "dissection method" principle. Using singular perturbation theory, we describe the sequence of bifurcations undergone by the regulating (FitzHugh-Nagumo) system, encompassing the rarely investigated case of homoclinic connexion. Basing on pure dynamical considerations, we restrict the space of parameter search for the regulating system and describe a foliation of this restricted space, whose leaves define constant duration ratios between the surge and the pulsatility phase in the whole system. We propose an algorithm to fix the parameter values to also meet the other prescribed ratios dealing with amplitude and frequency features of the secretion signal. We finally apply these results to illustrate the dynamics of GnRH secretion in the ovine species and the rhesus monkey