Didier Chesneau

French National Centre for Scientific Research, Lutetia Parisorum, Île-de-France, France

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Publications (38)135.98 Total impact

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    ABSTRACT: Regulation of neuroendocrine responses is often studied in animals housed indoors in individual contiguous pens. In sheep, these housing conditions are used to control the environment, facilitate biological sampling and limit social stress. However, this type of housing also prevents exploratory behaviors and could induce stereotypies, non-compliant with welfare and possibly associated with a state of stress. In this context, we investigated the impact of housing in a single-pen, with other familiar conspecifics, on emotional state by evaluating behavioral, hormonal and neuronal measures in adult ewes. We hypothesized that emotional state would be more negative in animals housed in a single-pen for one week (Pen) than in freely moving animals (Free) but less negative than in socially isolated subjects (Isol). We tested our hypothesis in ovariectomized ewes to avoid the interaction with sexual steroid variations. Our behavioral, endocrine and neuronal (Fos activation of the corticotropin-releasing hormone neurons in the paraventricular nucleus of the hypothalamus) measures confirmed that withdrawing familiar conspecifics was sufficient to induce strong stress responses in Isol ewes, but there was no indication that Pen ewes were stressed. However, the latter showed less mastication activity than Free ewes, probably due to limited accessibility to straw. The highest plasma prolactin levels were observed in Isol and Free animals, which might result from stress and physical activity, respectively. In Free ewes, plasma dopamine was low, consistent with its inhibitory control of prolactin. However, Isol animals had both high levels of prolactin and dopamine, suggesting a dysregulated balance in socially stressed ewes. As in other species, we suggest that the regulation of prolactin by dopamine varies with stress and/or social context. Overall, this study shows that the impact of housing conditions on different neuroendocrine systems should be considered more in the future. Copyright © 2015. Published by Elsevier Inc.
    Physiology & Behavior 04/2015; 147. DOI:10.1016/j.physbeh.2015.04.013 · 3.03 Impact Factor
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    ABSTRACT: The first ovulation induced by male effect in sheep during seasonal anoestrus usually results in the development of a short cycle that can be avoided by progesterone priming before ram introduction. In elucidating the involvement of the hypothalamic-pituitary-gonadal axis on the occurrence of short cycles, the effects of progesterone and the time of anoestrus on the development of male-induced preovulatory follicles were investigated in anoestrus ewes using morphological, endocrine and molecular approaches. Ewes were primed with progesterone for 2 (CIDR-2) or 12 days (CIDR-12) and untreated ewes used as controls during early (April) and late (June) anoestrus. The duration of follicular growth and the lifespan of the male-induced preovulatory follicles were prolonged by about 1.6 days in CIDR-12 ewes compared to the controls. These changes were accompanied by a delay in the preovulatory LH and FSH surges and ovulation. Intrafollicular oestradiol concentration and mRNA levels of LHCGR and STAR in the granulosa and theca cells of the preovulatory follicles were higher in CIDR-12 than the control ewes. The expression of mRNA levels of CYP11A1 and CYP17A1 also increased in theca cells of CIDR-12 ewes. CIDR-2 ewes gave intermediate results. Moreover, ewes ovulated earlier in June than April, without changes in the duration of follicular growth, but these effects were unrelated to the lifespan of corpus luteum. Our results give the first evidence supporting the positive effect of progesterone priming on the completion of growth and maturation of preovulatory follicles induced by male effect in seasonal anoestrus ewes, thereby preventing short cycles.
    Reproduction (Cambridge, England) 07/2014; 148(4). DOI:10.1530/REP-14-0263 · 3.26 Impact Factor
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    ABSTRACT: This study assessed the effect of melatonin deprival on ovarian status and function in sheep. Experimental procedures were carried out within two consecutive breeding seasons. Animals were divided into two groups: pinealectomized (n=6); sham-operated (n=6). The completeness of the pineal gland removal was confirmed by the plasma concentration of melatonin. Ovarian status was monitored by ovarian ultrasonography during one year to study reproductive seasonality. Follicles and corpora lutea growth dynamics were assessed during an induced oestrous cycle. Since melatonin effects on the ovary may be also mediated by its antioxidant properties, plasma trolox equivalent antioxidant capacity (TEAC) was determined monthly during one year. Pinealectomy significantly extended the breeding season (310 ± 24.7 vs 217.5 ± 24.7 days in controls; p<0.05). Both pinealectomized and sham-operated ewes showed a well-defined wave-like pattern of follicle dynamics; however, melatonin deficiency caused fewer waves during the oestrous cycle (4.3 ± 0.2 vs. 5.2 ± 0.2; p<0.05) because waves were one day longer when compared with the controls (7.2 ± 0.3 vs. 6.1 ± 0.3; p<0.05). The mean area of the corpora lutea (105.4 ± 5.9 vs. 65.4 ± 5.9 mm2; p<0.05) and progesterone plasma levels (7.1 ± 0.7 vs 4.9 ± 0.6 ng/mL; p<0.05) were significantly higher in sham-operated compared with pinealectomized ewes. In addition, TEAC values were significantly lower in pinealectomized ewes compared to control ones. These data suggest that melatonin, besides exerting its well-known role in the synchronization of seasonal reproductive fluctuations, also influences the growth pattern of the follicles and the steroidogenic capacity of the corpus luteum.
    Reproduction 02/2014; DOI:10.1530/REP-13-0405
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    ABSTRACT: The pineal gland secretes melatonin that circulates in the blood and cerebrospinal fluid. We provide data that support the hypothesis that, in sheep and maybe in human, only the cerebrospinal fluid melatonin, and not the blood melatonin, can provide most of melatonin to the cerebral tissue in high concentrations, particularly in the periventricular area. The melatonin content of sheep brain, our chosen animal model, was found in significant concentration gradients oriented from the ventricle (close to the cerebrospinal fluid) to the cerebral tissue, with concentrations varying by a factor of 1 to 125. The highest concentrations were observed close to the ventricle wall, whereas the lowest concentrations were furthest from the ventricles (407.0 ± 71.5 pg/ml compared to 84.7 ± 5.2 pg/ml around the third ventricle). This concentration gradient was measured in brain tissue collected at mid-day and at the end of the night. Nocturnal concentrations were higher than daytime concentrations, reflecting the diurnal variation in the pineal gland. The concentration gradient was not detected when melatonin was delivered to the brain via the bloodstream. The diffusion of melatonin to cerebral tissues via cerebrospinal fluid was supported by in vivo scintigraphy and autoradiography. 2-[(123) I]-melatonin infused into the cerebrospinal fluid quickly and efficiently diffused into the brain tissues, whereas [(123) I]-iodine (control) was mostly washed away by the cerebrospinal fluid flow and [(123) I]-BSA remained mostly in the cerebrospinal fluid. Taken together, these data support a critical role of cerebrospinal fluid in providing the brain with melatonin. This article is protected by copyright. All rights reserved.
    Journal of Neuroendocrinology 01/2014; 26(3). DOI:10.1111/jne.12134 · 3.51 Impact Factor
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    ABSTRACT: Kisspeptin has emerged as the most potent gonadotropin-releasing hormone (GnRH) secretagogue and appears to represent the penultimate step in the central control of reproduction. In the sheep, we showed that kisspeptin could be used to manipulate gonadotropin secretion and control ovulation. Prompted by these results we decided to investigate whether kisspeptin could be used as an ovulation-inducing agent in another photoperiodic domestic mammal, the horse. Equine kisspeptin-10 (eKp10) was administered intravenously as bolus injections or short to long-term perfusions to Welsh pony mares, either during the anestrus season or at various stages of the cycle during the breeding season. In all experimental conditions eKp10 reliably increased peripheral concentrations of both luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The nature of the response to eKp10 was consistent across experimental conditions and physiological states: the increase in gonadotropins was always rapid and essentially transient even when eKp10 was perfused for prolonged periods. Furthermore, eKp10 consistently failed to induce ovulation in the mare. To gain insights into the underlying mechanisms, we used acute injections or perfusions of GnRH. We also cloned the equine orthologues of the kisspeptin precursor and Kiss1r; this was justified by the facts that the current equine genome assembly predicted an amino acid difference between eKp10 and Kp10 in other species while an equine orthologue for Kiss1r was missing altogether. In light of these findings, potential reasons for the divergence in the response to kisspeptin between ewe and mare are discussed. Our data highlight that kisspeptin is not a universal ovulation-inducing agent.
    Biology of Reproduction 01/2014; 90(2). DOI:10.1095/biolreprod.113.114157 · 3.45 Impact Factor
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    46th Annual SSR Annual meeting reproductive health: Nano to Global (Society for the study of reproduction), Montréal, CANADA.; 07/2013
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    ABSTRACT: Sheep are gregarious mammals with complex social interactions. As such, they are very sensitive to social isolation and constitute a relevant animal model to study specifically the biological consequences of social stress. We examined previously the behavioral and endocrine responses in ewes isolated socially in the familiar conspecific withdrawal model (FCW) and showed that stressful responses increased and maintenance behaviors decreased, confirming that social isolation is a strong stressor in sheep. Melatonin synchronizes seasonal and circadian rhythms; and several studies reported its implication in cognitive processes as emotion. Here we investigated its role in the modulation of social stressful responses. Firstly, we studied ewes in the FCW model during the day (characterized by low melatonin levels) and the night (characterized by high melatonin levels). We found lower stressful responses (significant lower levels of cortisol plasma, number of foot pawings, of circling attempts) during the night as compared to the day. To investigate whether these effects were due to melatonin or to darkness, we submitted ewes to FCW during the night with lights on, a condition that suppresses melatonin secretion. Ewes infused with melatonin under these conditions showed decreased stressful responses (significant lower levels cortisol plasma, number of vocalizations, time spent with the head out of the cage) as compared to ewes infused with saline. These findings demonstrate that melatonin diminishes the endocrine and behavioral impact of social isolation in ewes and support the idea that melatonin has a calming effect in socially stressful situations.
    Psychoneuroendocrinology 01/2013; 38(8). DOI:10.1016/j.psyneuen.2012.12.011 · 5.59 Impact Factor
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    ABSTRACT: Influence de la durée d’un traitement progestatif sur la dynamique de croissance des follicules préovulatoires induits par effet mâle chez la brebis Ile de France en anœstrus saisonnier ADIB A. (1,2,3,4), FRERET S. (1,2,3,4), CHESNEAU D. (1,2,3,4), TOUZE J.L. (1,2,3,4), CHEMINEAU P. (1,2,3,4), PELLICER M.T. (1,2,3,4) 1) INRA, UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France 2) CNRS, UMR 7247, F-37380 Nouzilly, France 3) Université François Rabelais de Tours, F-37041 Tours, France 4) IFCE, F637380 Nouzilly, France RESUME: Dans le but d’évaluer l’effet de la durée du traitement progestatif (12 jours versus 2 jours) sur la dynamique de croissance des follicules préovulatoires induits par effet mâle, une expérience a été conduite sur 41 brebis anovulatoires de race Ile de France soumises à un effet mâle durant l’anœstrus saisonnier. Ces brebis ont été réparties en trois groupes homogènes : Groupe témoin : aucun traitement préalable (n=20). Groupe traité par des dispositifs vaginaux (CIDR-2) pendant 2 jours : traitement de courte durée (n=11). Groupe traité par des dispositifs vaginaux (CIDR-12) pendant 12 jours : traitement de longue durée (n=10). Le retrait des CIDR est réalisé 24h avant l’introduction des béliers (J0). L’effet mâle a été réalisé avec 9 béliers sexuellement actifs. La détection de l’œstrus est faite deux fois par jour. La durée du cycle induit a été déterminée par un suivi journalier de la progestérone plasmatique. Les paramètres de croissance des follicules préovulatoires induits par le mâle ont été analysés par échographie transrectale. Les résultats montrent que le traitement progestatif appliqué n’a aucune influence sur le pourcentage de brebis qui ovulent (98%). Comme attendu, toutes les brebis prétraitées avec CIDR qui ovulent développent des cycles de durée normale, avec 100% des brebis CIDR-12 qui viennent en chaleur à la première ovulation induite et seulement 20% des brebis CIDR-2. Les brebis témoins quant à elles, présentent majoritairement des cycles courts (80%) et n’expriment pas d’œstrus. La durée de croissance des follicules préovulatoires est plus importante (P=0,003) chez les brebis traitées pendant 12 jours (4,4 ± 0,3 jours) par rapport aux brebis traitées pendant 2 jours (3,2 ± 0,3 jours) et les brebis témoins (2,9 ± 0,2 jours). De la même façon, la durée de vie est prolongée (P=0,01) chez le groupe traité pendant 12 jours (5,7 ± 0,3 jours) par rapport aux groupe traité 2 jours (5,1 ± 0,4) et le groupe témoin (4,3 ± 0,3 jours). Ces résultats sont associés à une ovulation qui a lieu plus tardivement (P=0,08) chez les brebis traitées 12 jours (3,2 ± 0,7 jours) par rapport aux brebis traitées 2 jours (2,4 ± 0,3 jours) et brebis témoins (2,6 ± 0,2 jours). Cependant, les autres paramètres analysés ne différent pas entre groupes. Ces résultats suggèrent que la durée du traitement progestatif préalable à l’effet mâle affecte la qualité des follicules préovulatoires induits et permet une meilleure maturation folliculaire.
    .Annual International Francophone Congres : 19e Rencontres Recherches Ruminants (3R), Paris,France; 12/2012
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    Annual International Francophone Congres : 19e Rencontres Recherches Ruminants (3R), Paris, France; 12/2012
  • the Frontiers in Stress and cognition meeting: from Molecules to Behavior; 09/2012
  • 28th Annual Scientific Meeting of the European Embryo Transfer Association (A.E.T.E), Saint Malo, France; 09/2012
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    ABSTRACT: In sheep, the seasonal patterns of reproductive activity are driven primarily by the annual photoperiodic cycle, but can also respond to other environmental factors, such as nutrition, yet little is known about the mechanisms underlying this interaction. This study was designed to define the interaction between photoperiodic and nutritional cues on seasonal patterns of ovarian activity, and to determine if there is a central interaction between these cues. Groups of Ile-de-France ewes were maintained in two nutritional states (restricted and well fed) under a simulated annual photoperiod of 8-16 h of light per day over two breeding seasons. At the end of the first breeding season, half of the animals of each group were ovariectomized (OVX) and fitted subcutaneously with estradiol implants. Low nutritional status shortened the season of ovarian activity, determined from the pattern of progesterone concentrations, by modifying the timing of seasonal transitions between periods of ovarian activity and anestrus. The same results were observed for the seasonal rhythm of neuroendocrine activity, assessed in the OVX ewes, from the pattern of luteinizing hormone concentrations. These results were then confirmed for neuroendocrine activity induced by a photoperiodic treatment. We conclude that nutrition centrally modulates the interpretation of photoperiod to affect seasonal reproductive transitions. The mechanisms of this interaction are discussed in the paper.
    Biology of Reproduction 11/2011; 86(2):52. DOI:10.1095/biolreprod.111.092817 · 3.45 Impact Factor
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    ABSTRACT: Mares have an annual reproductive rhythm, with a phase of inactivity in midwinter. The aim of this study was to determine the impact of food restriction on physiological and metabolic hallmarks of this rhythm. Over three successive years, 3 groups of 10 mares were kept under natural photoperiod. A 'well-fed' group was fed to maintain the mares in good body condition; a 'restricted' group received a diet calculated to keep the mares thin and a 'variable' group was fed during some periods like the 'restricted' group and during some other periods like the 'well-fed' group, with the aim of mimicking the natural seasonal variation of pasture availability, but a few months in advance of this natural rhythm. Winter ovarian inactivity always occurred and was long in the restricted group. In contrast, in the 'well-fed' group, 40% of mares showed this inactivity, which was shorter than in the other groups. Re-feeding the 'variable' group in autumn and winter did not advance the first ovulation in spring, compared with the 'restricted' group. Measurements of glucose and insulin concentrations in mares from the 'restricted' group during two 24 h periods of blood sampling, revealed no post-prandial peaks. For GH (Growth hormone), IGF-1 and leptin levels, large differences were found between the 'well-fed' group and the other groups. The glucose, insulin, GH and leptin levels but not melatonin level are highly correlated with the duration of ovulatory activity. The annual rhythm driven by melatonin secretion is only responsible for the timing of the breeding season. The occurrence and length of winter ovarian inactivity is defined by metabolic hormones.
    Reproductive Biology and Endocrinology 09/2011; 9(1):130. DOI:10.1186/1477-7827-9-130 · 2.41 Impact Factor
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    ABSTRACT: It is now widely accepted that AMP-activated protein kinase (AMPK) is a critical regulator of energy homeostasis. Recently, it has been shown to regulate circadian clocks. In seasonal breeding species such as sheep, the circadian clock controls the secretion of an endogenous rhythm of melatonin and, as a consequence, is probably involved in the generation of seasonal rhythms of reproduction. Considering this, we identified the presence of the subunits of AMPK in different hypothalamic nuclei involved in the pre- and post-pineal pathways that control seasonality of reproduction in the ewe and we investigated if the intracerebroventricular (i.c.v.) injection of two activators of AMPK, metformin and AICAR, affected the circadian rhythm of melatonin in ewes that were housed in constant darkness. In parallel the secretion of insulin was monitored as a peripheral metabolic marker. We also investigated the effects of i.c.v. AICAR on the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), a downstream target of AMPK, in brain structures along the photoneuroendocrine pathway to the pineal gland. All the subunits of AMPK that we studied were identified in all brain areas that were dissected but with some differences in their level of expression among structures. Metformin and AICAR both reduced (p < 0.001 and p < 0.01 respectively) the amplitude of the circadian rhythm of melatonin secretion independently of insulin secretion. The i.c.v. injection of AICAR only tended (p = 0.1) to increase the levels of phosphorylated AMPK in the paraventricular nucleus but significantly increased the levels of phosphorylated ACC in the paraventricular nucleus (p < 0.001) and in the pineal gland (p < 0.05). Taken together, these results suggest a potential role for AMPK on the secretion of melatonin probably acting trough the paraventricular nucleus and/or directly in the pineal gland. We conclude that AMPK may act as a metabolic cue to modulate the rhythm of melatonin secretion.
    BMC Neuroscience 07/2011; 12:76. DOI:10.1186/1471-2202-12-76 · 2.85 Impact Factor
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    ABSTRACT: In seasonal breeding species, the gene encoding for the melatonin MT(1) receptor (oMT(1)) is highly polymorphic and numerous data have reported the existence of an association between an allele of the receptor and a marked expression of the seasonality of reproduction in ewes. This allele called "m" (previously named "-" allele) carries a mutation leading to the absence of a MnlI restriction site as opposed to the "M" allele (previously named "+" allele) carrying the MnlI restriction site (previously "+" allele). This allows the determination of the three genotypes "M/M" (+/+), "M/m" (+/-) and "m/m" (-/-). This mutation is conservative and could therefore not be causal. However, it is associated with another mutation introducing the change of a valine to an isoleucine in the fifth transmembrane domain of the receptor. Homozygous "M/M" and "m/m" animals consequently express structurally different receptors respectively named oMT(1) Val(220) and oMT(1) Ile(220). The objective of this study was to test whether these polymorphic variants are functionally different. To achieve this goal, we characterized the binding properties and the transduction pathways associated with both variants of the receptors. Using a pharmacological approach, no variation in binding parameters between the two receptors when transiently expressed in COS-7. In stably transfected HEK293 cells, significant differences were detected in the inhibition of cAMP production whereas receptors internalization processes were not different. In conclusion, the possibility that subtle alterations induced by the non conservative mutation in "m/m" animals might modify the perception of the melatoninergic signal is discussed in the context of melatonin action.
    Animal reproduction science 10/2010; 122(3-4):328-34. DOI:10.1016/j.anireprosci.2010.10.007 · 1.58 Impact Factor
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    ABSTRACT: For a better understanding of the mechanisms that lead to the preovulatory GnRH/LH surge and estrus behavior, the minimum estradiol (E) requirements (dose and duration) to induce each of these events were determined and compared between two breeds of ewes having either single (Ile de France) or multiple (Romanov) ovulations. The ewes were initially studied during a natural estrus cycle, and were then ovariectomized and run through successive artificial estrus cycles. For these artificial cycles the duration and amplitude of the follucular phase E increase were manipulated by E implants. Under all conditions, the onset of estrus behavior was similar in the two breeds, although its duration was longer in Romanov ewes. While a moderate E signal (6 cm for 12 h) induced an LH surge in 10/10 Ile de France ewes, a larger E signal (12 cm for 12 h) was minimally effective in Romanov ewes (4/10). Additional studies revealed that a small E signal (3 cm for 6 h) induced full estrus behavior in all Romanov ewes but was completely ineffective in Ile de France animals (0/10). Higher doses and mostly longer durations of the E signal (12 cm for 24 h) were required to induce a surge in all the Romanov ewes. These results demonstrate a clear difference in the E requirement for the induction of estrus behavior and the LH surge between breeds of ewes that have different ovulation rates. These data provide compelling evidence that, in one breed, the neuronal systems that regulate both events require different estrogen signals.
    Biology of Reproduction 05/2007; 76(4):673-80. DOI:10.1095/biolreprod.106.057406 · 3.45 Impact Factor
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    Frontiers in Neuroendocrinology 05/2006; 27(1):130. DOI:10.1016/j.yfrne.2006.03.312 · 7.58 Impact Factor
  • Céline Legros · Serge Bernard · Didier Chesneau · Benoît Malpaux
    Frontiers in Neuroendocrinology 05/2006; 27(1):130-130. DOI:10.1016/j.yfrne.2006.03.311 · 7.58 Impact Factor
  • Reproduction Nutrition Development 07/2005; DOI:10.1051/rnd:2005042 · 2.17 Impact Factor
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    ABSTRACT: The gene encoding the MT1 melatonin receptor in sheep has a restriction fragment length polymorphism (RFLP) site to the MnlI enzyme whose incidence is associated to the expression of seasonality in several breeds. The aim of this study was to examine the relationship between this genetic marker and the physiological effects of MT1 receptor gene polymorphism on several seasonal functions in Ile-de-France ewes. The study was performed using 12 pairs of half-sib adult Ile-de-France ewes. Within each pair, ewes were selected on the basis of their genotype at the MnlI RFLP site: group +/+ and -/- (presence and absence of MnlI restriction site, respectively). No difference in the dates of the beginning, the end or the length of the breeding season was observed between groups during the two-year study. The seasonal changes in prolactin secretion were not different between groups. Similarly, wool growth rate and primary follicle activity, measured for one year, varied with the time of the year in the same way in the two groups. Our study therefore failed to show any relationship between MT1 polymorphism and reproductive seasonality in Ile-de-France ewes. This suggests that the influence of this polymorphism on the regulation of seasonal function is dependent upon the breed and/or environmental conditions. The MT1 polymorphism can explain only a small part of the genetic variability of seasonal functions and the implication of other genes must be investigated.
    Reproduction Nutrition Development 03/2005; 45(2):151-62. DOI:10.1051/rnd:2005012 · 2.17 Impact Factor

Publication Stats

472 Citations
135.98 Total Impact Points

Institutions

  • 2003–2015
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 2003–2014
    • University of Tours
      • UMR CNRS 7247 Physiologie de la Reproduction et des Comportements (PRC)
      Tours, Centre, France
  • 2013
    • French National Institute for Agricultural Research
      • Physiologie de la Reproduction et des Comportements (PRC)
      Lutetia Parisorum, Île-de-France, France
  • 1989
    • University of Zurich
      Zürich, Zurich, Switzerland