CNRS Physiology of Reproduction and Behaviors

Tours, France

CNRS Physiology of Reproduction and Behaviors

Tours, France
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Gomes I.,Mount Sinai School of Medicine | Ayoub M.A.,CNRS Physiology of Reproduction and Behaviors | Ayoub M.A.,LE STUDIUM Loire Valley Institute for Advanced Studies | Fujita W.,Mount Sinai School of Medicine | And 7 more authors.
Annual Review of Pharmacology and Toxicology | Year: 2016

G protein-coupled receptors (GPCRs) compose one of the largest families of membrane proteins involved in intracellular signaling. They are involved in numerous physiological and pathological processes and are prime candidates for drug development. Over the past decade, an increasing number of studies have reported heteromerization between GPCRs. Many investigations in heterologous systems have provided important indications of potential novel pharmacology; however, the physiological relevance of these findings has yet to be established with endogenous receptors in native tissues. In this review, we focus on family A GPCRs and describe the techniques and criteria to assess their heteromerization. We conclude that advances in approaches to study receptor complex functionality in heterologous systems, coupled with techniques that enable specific examination of native receptor heteromers in vivo, are likely to establish GPCR heteromers as novel therapeutic targets. Copyright © 2016 by Annual Reviews. All rights reserved.


Reiter E.,CNRS Physiology of Reproduction and Behaviors | Reiter E.,French National Center for Scientific Research | Reiter E.,University of Tours | Reiter E.,Institute Francais Du Cheval Et Of Lequitation | And 5 more authors.
Annual Review of Pharmacology and Toxicology | Year: 2012

The concept of biased agonism has recently come to the fore with the realization that seven-transmembrane receptors (7TMRs, also known as G proteincoupled receptors, or GPCRs) activate complex signaling networks and can adopt multiple active conformations upon agonist binding. As a consequence, the "efficacy" of receptors, which was classically considered linear, is now recognized as pluridimensional. Biased agonists selectively stabilize only a subset of receptor conformations induced by the natural "unbiased" ligand, thus preferentially activating certain signaling mechanisms. Such agonists thus reveal the intriguing possibility that one can direct cellular signaling with unprecedented precision and specificity and support the notion that biased agonists may identify new classes of therapeutic agents that have fewer side effects. This review focuses on one particular class of biased ligands that has the ability to alter the balance between G proteindependent and β-arrestin-dependent signal transduction. © 2012 by Annual Reviews. All rights reserved.


Geller S.,CNRS Physiology of Reproduction and Behaviors | Kolasa E.,CNRS Physiology of Reproduction and Behaviors | Kolasa E.,University of Rennes 1 | Tillet Y.,CNRS Physiology of Reproduction and Behaviors | And 2 more authors.
GLIA | Year: 2013

During development, GnRH-1 neurons differentiate extracerebraly from the nasal placode and migrate from the vomeronasal organ to the forebrain along vomeronasal and terminal nerves. Numerous studies have described the influence of different molecules on the migration of GnRH-1 neurons, however, the role of microenvironment cells remains poorly understood. This study used GFAP-GFP transgenic mice to detect glial cells at early developmental stages. Using nasal explant cultures, the comigration of glial cells with GnRH-1 neurons was clearly demonstrated. This in vitro approach showed that glial cells began migrating from the explants before GnRH-1 neurons. They remained ahead of the GnRH-1 migratory front and stopped migrating after the GnRH-1 neurons. The association of these glial cells with the axons combined with gene expression analysis of GFAP-GFP sorted cells enabled them to be identified as olfactory ensheathing cells (OEC). Immunohistochemical analysis revealed the presence of multiple glial cell-type markers showing several OEC subpopulations surrounding GnRH-1 neurons. Moreover, these OEC expressed genes whose products are involved in the migration of GnRH-1 neurons, such as Nelf and Semaphorin 4. In situ data confirmed that the majority of the GnRH-1 neurons were associated with glial cells along the vomeronasal axons in nasal septum and terminal nerves in the nasal forebrain junction as early as E12.5. Overall, these data demonstrate an OEC microenvironment for migrating GnRH-1 neurons during mouse development. The fact that this glial cell type precedes GnRH-1 neurons and encodes for molecules involved in their nasal migration suggests that it participates in the GnRH-1 system ontogenesis. © 2013 Wiley Periodicals, Inc.


Combarnous Y.,CNRS Physiology of Reproduction and Behaviors
Comptes Rendus - Biologies | Year: 2017

A number of pesticides are suspected or proved to act as endocrine disruptor compounds (EDCs). In the present survey of the literature, we try to define the main issues to be considered to classify individual pesticides as EDC or not. © 2017 Académie des sciences.


Nguyen T.M.D.,CNRS Physiology of Reproduction and Behaviors | Nguyen T.M.D.,Quy Nhon University
Frontiers in Cell and Developmental Biology | Year: 2017

As we already know, the male reproductive system requires less energetic investment than the female one. Nevertheless, energy balance is an important feature for spermatozoa production in the testis and for spermatozoa properties after ejaculation. The 5'-AMP-activated protein kinase, AMPK, is a sensor of cell energy, that regulates many metabolic pathways and that has been recently shown to control spermatozoa quality and functions. It is indeed involved in the regulation of spermatozoa quality through its action on the proliferation of testicular somatic cells (Sertoli and Leydig), on spermatozoa motility and acrosome reaction. It also favors spermatozoa quality through the management of lipid peroxidation and antioxidant enzymes. I review here the most recent data available on the roles of AMPK in vertebrate spermatozoa functions. © 2017 Nguyen.


Clarke I.J.,Monash University | Caraty A.,CNRS Physiology of Reproduction and Behaviors
Advances in Experimental Medicine and Biology | Year: 2013

Wild and domesticated species display seasonality in reproductive function, controlled predominantly by photoperiod. Seasonal alterations in breeding status are caused by changes in the secretion of gonadotropin-releasing hormone (GnRH) that are mediated by upstream neuronal afferents that regulate the GnRH cells. In particular, kisspeptin appears to play a major role in seasonality of reproduction, transducing the feedback effect of gonadal steroids as well as having an independent (nonsteroid dependent) circannual rhythm. A substantial body of data on this issue has been obtained from studies in sheep and hamsters and this is reviewed here in detail. Kisspeptin function is upregulated during the breeding season in sheep, stimulating reproductive function, but contradictory data are found in Siberian and Syrian hamsters. The relative quiescence of kisspeptin cells in the nonbreeding season can be counteracted by administration of the peptide, leading to activation of reproductive function. Although there is a major role for melatonin in the transduction of photoperiod to the reproductive system, kisspeptin cells do not appear to express the melatonin receptor, so the means by which seasonality changes the level of kisspeptin activity remains unknown. © Springer Science+Business Media, LLC 2013.


Dardente H.,CNRS Physiology of Reproduction and Behaviors
Journal of Neuroendocrinology | Year: 2012

Most mammals living at temperate latitudes exhibit marked seasonal variations in reproduction. In long-lived species, it is assumed that timely physiological alternations between a breeding season and a period of sexual rest depend upon the ability of day length (photoperiod) to synchronise an endogenous timing mechanism called the circannual clock. The sheep has been extensively used to characterise the time-measurement mechanisms of seasonal reproduction. Melatonin, secreted only during the night, acts as the endocrine transducer of the photoperiodic message. The present review is concerned with the endocrine mechanisms of seasonal reproduction in sheep and the evidence that long day length and thyroid hormones are mandatory to their proper timing. Recent evidence for a circadian-based molecular mechanism within the pars tuberalis of the pituitary, which ties the short duration melatonin signal reflecting long day length to the hypothalamic increase of triiodothyronine (T3) through a thyroid-stimulating hormone/deiodinase2 paracrine mechanism is presented and evaluated in this context. A parallel is also drawn with the golden hamster, a long-day breeder, aiming to demonstrate that features of seasonality appear to be phylogenetically conserved. Finally, potential mechanisms of T3 action within the hypothalamus/median eminence in relationship to seasonal timing are examined. © 2011 The Author. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.


Druart X.,CNRS Physiology of Reproduction and Behaviors
Reproduction in Domestic Animals | Year: 2012

Sperm transit in the female tract is a critical event for the success of fertilization. From their deposition in the vagina to final migration in the oviduct, sperm pass through the different compartments of the genital tract in which they encounter different environments. The cervix and the uterotubal junction (UTJ) are two barriers with different relative importance according to the species. The protein composition, the degree of glycosylation and the hydration of the cervical mucus change during the oestrous cycle. Several sperm surface proteins are associated with their migration through the cervical mucus and the UTJ. Data regarding the interaction of sperm with secretions of the epithelial tissue lining the different compartments of the female genital tract during the sperm transit are reviewed, with a particular emphasis on the migration of sperm through the cervix. © 2012 Blackwell Verlag GmbH.


Dacheux J.-L.,CNRS Physiology of Reproduction and Behaviors | Dacheux F.,CNRS Physiology of Reproduction and Behaviors
Reproduction | Year: 2014

Testicular spermatozoa acquire fertility only after 1 or 2 weeks of transit through the epididymis. At the end of this several meters long epididymal tubule, the male gamete is able to move, capacitate, migrate through the female tract, bind to the egg membrane and fuse to the oocyte to result in a viable embryo. All these sperm properties are acquired after sequential modifications occurring either at the level of the spermatozoon or in the epididymal surroundings. Over the last few decades, significant increases in the understanding of the composition of the male gamete and its surroundings have resulted from the use of new techniques such as genome sequencing, proteomics combined with high-sensitivity mass spectrometry, and gene-knockout approaches. This review reports and discusses the most relevant new results obtained in different species regarding the various cellular processes occurring at the sperm level, in particular, those related to the development of motility and egg binding during epididymal transit. © 2014 Society for Reproduction and Fertility.


Dardente H.,CNRS Physiology of Reproduction and Behaviors
Current Biology | Year: 2015

Endogenous long-term timing is a key component of seasonality. Where and how are such rhythms generated? Recent findings pointed to the pituitary pars tuberalis, already implicated in photoperiod responsiveness. Now, a new study provides mechanistic insights which support this hypothesis. © 2015 Elsevier Ltd.

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