Publications (15)37.02 Total impact
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Dataset: Scaramuzzi Fig 3 Follicle cascade
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Article: Significant differences in fertility between dairy cows selected for one QTL located on bovine chromosome 3 are not attributable to energy balance, although eating behaviour is affected.
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ABSTRACT: Improvement of reproduction in dairy cows has become a major challenge in dairy production. We have recently shown that dairy cows carrying the 'fertil-' haplotype for one quantitative trait locus (QTL), affecting female fertility and located on the bovine chromosome 3, had a significantly lower conception rate after the first artificial insemination than cows carrying the 'fertil+' haplotype. The objective of this paper was to study other phenotypic modifications linked to this QTL. In the present study, 23 'fertil+' and 18 'fertil-' cows were characterized for live weight, milk production, food intake, eating behaviour and plasma metabolites. These parameters were measured during the first lactation, from calving to 40 weeks postpartum (wkpp). In the first 7 weeks of lactation, 'fertil+' primiparous cows had a significantly higher live BW and milk production than 'fertil-' cows. Dry matter intake tended to be slightly higher for 'fertil+' than for 'fertil-' primiparous cows in this period. However, energy balance was similar for the two haplotypes in the whole lactation, except in the first wkpp, and consequently, could not explain their different fertility. The major observation concerned the eating behaviour. 'Fertil+' primiparous cows had a significantly lower eating rate than 'fertil-' cows during the 40 weeks of lactation. In parallel, 'fertil+' cows spent significantly more time at the feeder for a similar number of visits than 'fertil-' cows. Furthermore, no differences in plasma concentrations of non-esterified fatty acids and insulin were observed between the two haplotypes. Plasma glucose was significantly lower in 'fertil+' than in 'fertil-' cows in the second wkpp. Taken together, our results show that 'fertil+' and 'fertil-' dairy cows, with different fertility, have also different eating behaviour without any variation in energy balance, except in the first week of lactation.animal 11/2012; · 1.74 Impact Factor -
Article: Analysis of in vivo oocyte maturation, in vitro embryo development and gene expression in cumulus cells of dairy cows and heifers selected for one fertility quantitative trait loci (QTL) located on BTA3.
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ABSTRACT: We have previously shown that Holstein cows selected for their homozygous favorable ("fertil+") or unfavorable ("fertil-") haplotype at one quantitative trait loci (QTL) of female fertility located on chromosome 3 (QTL-F-Fert-BTA3) had a different success rate 35 and 90 days after the first artificial insemination. To determine whether the lower fertility in "fertil-" animals could be related to oocyte quality, we analyzed the embryo development rate in vitro and the oocyte meiotic maturation in vivo in "fertil+" and "fertil-" heifers. In vitro maturation and fertilization of immature oocytes recovered by ovum pick-up from "fertil+" and "fertil-" heifers resulted in similar cleavage and blastocyst rates in the two haplotypes. However the percentage of expanded blastocysts and the number of cells per blastocyst were significantly higher in "fertil+". Oocytes from presumptive preovulatory follicles were analyzed after ovarian stimulation. A similar rate of immature (from prophase to metaphase-I) and mature oocytes (metaphase-II) was obtained in the two haplotypes, whereas a significantly higher percentage of oocytes from metaphase-I to metaphase-II was observed in "fertil+" compared to "fertil-" heifers. Since cumulus cells (CCs) could reflect the developmental competence of oocytes, we analyzed the expression of seven genes included in the QTL-F-Fert-BTA3 using real-time PCR in bovine CCs after in vivo or in vitro maturation, as a model of higher and lower competence, respectively. Transcript levels of TAGLN2, EEF1A1 and PIGM were higher in CCs after in vitro maturation (IVM) compared to in vivo maturation, whereas no difference was observed for IFI16, KIRREL, SPTA1 and PEX19 expression. The expression levels of all these genes in in preovulatory CCs were not significantly different between "fertil+" and "fertil-" heifers. In conclusion, the lower fertility of "fertil-" females could be partially due to a lowest quality of the oocytes and consequently of preimplantation embryo development.Theriogenology 03/2012; 77(9):1822-33.e1. · 1.96 Impact Factor -
Article: Regulation of folliculogenesis and the determination of ovulation rate in ruminants.
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ABSTRACT: The paper presents an update of our 1993 model of ovarian follicular development in ruminants, based on knowledge gained from the past 15 years of research. The model addresses the sequence of events from follicular formation in fetal life, through the successive waves of follicular growth and atresia, culminating with the emergence of ovulatory follicles during reproductive cycles. The original concept of five developmental classes of follicles, defined primarily by their responses to gonadotrophins, is retained: primordial, committed, gonadotrophin-responsive, gonadotrophin-dependent and ovulatory follicles. The updated model has more extensive integration of the morphological, molecular and cellular events during folliculogenesis with systemic events in the whole animal. It also incorporates knowledge on factors that influence oocyte quality and the critical roles of the oocyte in regulating follicular development and ovulation rate. The original hypothetical mechanisms determining ovulation rate are retained but with some refinements; the enhanced viability of gonadotrophin-dependent follicles and increases in the number of gonadotrophin-responsive follicles by increases in the throughput of follicles to this stage of growth. Finally, we reexamine how these two mechanisms, which are thought not to be mutually exclusive, appear to account for most of the known genetic and environmental effects on ovulation rate.Reproduction Fertility and Development 04/2011; 23(3):444-67. · 2.11 Impact Factor -
Article: Ovarian parameters and fertility of dairy cows selected for one QTL located on BTA3.
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ABSTRACT: Recently, one Quantitative Trait Locus (QTL) of female fertility located on Bos Taurus chromosome 3 (BTA3), QTL-F-Fert-BTA3, has been identified in Holstein breed. It is implied in the success rate after the first AI (AI1) in cow. The failure of pregnancy can be due to several factors involved in the different steps of the reproductive process. The aim of our study was to finely phenotype heifers and primiparous cows selected for their haplotype at the QTL-F-Fert-BTA3. We specifically studied the ovarian follicular dynamic and several fertility parameters. Females carrying the favourable haplotype "fertil+" or unfavourable haplotype "fertil-" were monitored by transrectal ultrasonography during their cycle before the first AI (AI1). Follicular dynamic was similar between the two groups. However, the length of the estrus cycle was shorter in heifers than in primiparous cows and two-wave cycles were shorter than three-wave cycles, regardless of the age and the haplotype. The concentration of plasma anti-Müllerian hormone was correlated with the number of small antral follicles. It was higher in heifers than in primiparous cows, independently of their haplotype. The success rate at the AI1 was significantly higher in "fertil+" than in "fertil-" primiparous cows, 35 d after the AI1 (70% vs 39%). In both haplotypes, pregnancy failure occurred mainly before 21 d after AI1. The commencement of luteal activity after calving was significantly earlier in "fertil+" than in "fertil-" primiparous cows. Calving-AI1 and calving-calving intervals were similar between "fertil+" and "fertil-" primiparous cows. Taken together, "fertil+" and "fertil-" primiparous cows present a difference in the success rate after AI1 that is not explained by variations of ovarian dynamics.Theriogenology 12/2010; 75(7):1239-50. · 1.96 Impact Factor -
Article: Effects of unsaturated fatty acids on progesterone secretion and selected protein kinases in goat granulosa cells.
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ABSTRACT: Previous studies in cattle have shown influences of dietary unsaturated fatty acid (UFA) supplementation on ovarian function. However, it is unclear whether these UFA exert direct or indirect effects on ovarian steroid production or their mechanisms of action. We have recently shown that 5'AMP-activated protein kinase (AMPK) regulates progesterone secretion through mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 (MAPK ERK1/2) in rodent granulosa cells. Here, we investigated the effects of 3 UFAs, oleic acid (OA), linoleic acid (LA), and alpha-linolenic acid (ALA) on progesterone secretion in goat granulosa cells. Finally, we examined the effects of UFAs on MAPK ERK1/2 and AMPK phosphorylation in these granulosa cells. Oleic acid and LA (10 microM each), but not ALA (100 microM), increased progesterone secretion (P<0.05) in the presence or absence of insulin-like growth factor (IGF)-1 (10(-8) M) or FSH (5 x 10(-8)M). The different AMPK subunits, except for gamma3, are present in the goat ovary. Treatment with metformin (10mM), an activator of AMPK, increased AMPK phosphorylation (P<0.05) and reduced progesterone secretion by 50% (P<0.05) in the basal state and in response to IGF-1 or FSH in goat granulosa cells. Oleic acid and LA had no effect on AMPK phosphorylation, whereas they rapidly increased MAPK ERK1/2 phosphorylation (P<0.05). Finally, U0126, a MAPK ERK1/2 inhibitor, decreased OA- and LA-induced progesterone secretion (P<0.05), suggesting that these UFAs could stimulate progesterone secretion partly through MAPK ERK1/2 in the absence of IGF-1 and FSH in goat granulosa cells. The involvement of AMPK in this process remains to be demonstrated. Taken together, some fatty acids could improve ovarian steroidogenesis through the MAPK ERK1/2 signaling pathway and, consequently, have beneficial effects on goat fertility.Domestic animal endocrinology 05/2010; 38(4):272-83. · 1.65 Impact Factor -
Article: Role of adiponectin receptors, AdipoR1 and AdipoR2, in the steroidogenesis of the human granulosa tumor cell line, KGN.
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ABSTRACT: Adiponectin is involved in the regulation of energy homeostasis and more recently in the reproductive functions. We have previously shown that adiponectin receptors (AdipoR1 and AdipoR2) are expressed in human granulosa cells. However, it remains to be investigated whether both AdipoR1 and AdipoR2 or only one of these receptors serve as the major receptor(s) for adiponectin in human granulosa cells. The RNA interference (RNAi) technology was used to specifically knockdown the expression of either AdipoR1 or AdipoR2. Progesterone and estradiol levels in the conditioned media were measured by radioimmunoassay, and determination of cell proliferation by tritiated thymidine incorporation. The levels of adiponectin receptors and proteins involved in the steroidogenesis and in the signalling pathways were examined by western blot. We generated AdipoR1 (R1) and AdipoR2 (R2) knockdown KGN cell lines. R1 cells were apoptotic and had increased expression levels of cleaved caspase 3 and decreased levels of BAD phosphorylation and PCNA as compared with control or parental KGN cells. R2 cells had similar morphology to control or KGN cells. However, they produced less progesterone and estradiol and expressed lower levels of StAR protein in response to FSH or IGF-1 stimulation compared with control cells. Furthermore, the increase of MAPK ERK1/2 phosphorylation in response to human recombinant adiponectin and FSH was lower in R2 than control cells. In the human granulosa KGN cell-line, AdipoR1 seems to be involved in the cell survival whereas AdipoR2, through MAPK ERK1/2 activation, may be implicated in the regulation of steroid production.Human Reproduction 09/2009; 24(11):2890-901. · 4.47 Impact Factor -
Article: [Role of the fatty acids in ovarian functions: involvement of peroxisome proliferator-activated receptors (PPAR) and adipokines].
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ABSTRACT: The impact of nutrition and energy reserves on the reproductive functions is known for a very long time. However, the metabolic factors involved in the interactions between nutrition and reproduction are still poorly understood. These factors may be hormones or nutrients (glucose, protein and fatty acids). However, it remains to determine whether these factors act directly or indirectly on the reproductive tissues. In this issue, we briefly summarize the impact of fatty acids on the development of ovarian follicles, oocyte and embryo. We then discuss the current hypotheses about the mechanisms of action of these fatty acids on the ovarian functions. We describe more particularly the role of some receptors of fatty acids, Peroxisome Proliferator-Activated Receptors (PPAR) and Liver X Receptors (LXR) and two adipokines, leptin and adiponectin on ovarian cells.Gynécologie Obstétrique & Fertilité 12/2008; 36(12):1230-8. · 0.52 Impact Factor -
Article: The effect of AMP-activated kinase activation on gonadotrophin-releasing hormone secretion in GT1-7 cells and its potential role in hypothalamic regulation of the oestrous cyclicity in rats.
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ABSTRACT: Hypothalamic AMP-activated kinase (AMPK) is a key regulator of food intake in mammals. Its role in reproduction at the central level and, more precisely, in gonadotrophin-releasing hormone (GnRH) release has never been investigated. We showed that each subunit of AMPK is present in immortalised GnRH neurones (GT1-7 cells). Treatment with 5-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside (AICAR) and metformin, two activators of AMPK, increased dose-dependent and time-dependent phosphorylation of AMPKalpha atThr172 in GT1-7 cells. Phosphorylation of acetyl-coenzyme A carboxylase at ser79 also increased. Treatment with AICAR (5 mM) or metformin (5 mM) for 4 h inhibited GnRH release in the presence or absence of GnRH (10(-8) M). Specific AMPK inhibitor compound C completely eliminated the effects of AICAR or metformin on GnRH release. Finally, we determined the central effects of AICAR in vivo on food intake and oestrous cyclicity. Ten-week-old female rats received a 50 microg AICAR or a saline i.c.v. injection. We detected increased AMPK and acetyl-CoA carboxylase phosphorylation, specifically in the hypothalamus, 30 min after AICAR injection. Food intake was significantly higher (P < 0.05) in animals treated with AICAR than in animals injected with saline, 24 h after injection. This effect was abolished after 1 week. Moreover, during the 4 weeks following injection, the interval between two oestrous stages was significantly lower in the AICAR group than in the saline group. Our findings suggest that AMPK activation may act directly at the hypothalamic level to affect fertility by modulating GnRH release and oestrous cyclicity.Journal of Neuroendocrinology 03/2008; 20(3):335-46. · 3.14 Impact Factor -
Article: The effect of AMPK activation on GnRH secretion in GT1-7 cells and its potential role in hypothalamic regulation of the oestrous cyclicity in rats.
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ABSTRACT: Hypothalamic AMP-activated kinase (AMPK) is a key regulator of food intake in mammals. Its role in reproduction at the central level and more precisely in GnRH release has never been investigated. We showed that each subunit of AMPK is present in immortalised GnRH neurones (GT1-7 cells). Treatment with 5-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside (AICAR) and metformin, two activators of AMPK, increased dose-dependent and time-dependent phosphorylation of AMPKalpha atThr172 in GT1-7 cells. Phosphorylation of acetyl-coenzyme A carboxylase at ser79 also increased. Treatment with AICAR (5 mM) or metformin (5 mM) for 4h inhibited GnRH release in the presence or absence of GnRH (10(-8)M). Specific AMPK inhibitor compound C completely eliminated the effects of AICAR or metformin on GnRH release. Finally, we determined the central effects of AICAR in vivo on food intake and oestrous cyclicity. Ten-week-old female rats received a 50 mug AICAR or a saline intracerebroventricular (i.c.v.) injection. We detected increased AMPK and ACC phosphorylation, specifically in the hypothalamus, thirty minutes after the AICAR injection. Food intake was significantly higher (p<0.05) in animals treated with AICAR than in animals injected with saline, 24h after injection. This effect was abolished after one week. Moreover, during the four weeks following injection, the interval between two oestrous stages was significantly lower in the AICAR group than in the saline group. Our findings suggest that AMPK activation may act directly at the hypothalamic level to affect fertility by modulating GnRH release and oestrous cyclicity.Journal of Neuroendocrinology 02/2008; · 3.14 Impact Factor -
Article: Expression and biological effects of bone morphogenetic protein-15 in the hen ovary.
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ABSTRACT: The bone morphogenetic protein 15 (Bmp15) and growth differentiation factor 9 (Gdf9) genes are two members of the transforming growth factor-beta superfamily. In mammals, these genes are known to be specifically expressed in oocytes and to be essential for female fertility. However, potential ovarian roles of BMPs remain unexplored in birds. The aim of the present work was to study for the first time the expression of Bmp15 in the hen ovary, to compare its expression pattern with that of Gdf9, and then to investigate the effects of BMP15 on granulosa cell (GC) proliferation and steroidogenesis. We found that chicken Bmp15 and Gdf9 genes were preferentially expressed in the ovary. We showed using in situ hybridization that Bmp15 and Gdf9 mRNAs were specifically localized in oocytes of all ovarian follicles examined. We also demonstrated using real-time quantitative RT-PCR that Bmp15 and Gdf9 expression was maintained during hierarchical follicular maturation in the gerrminal disc region and then progressively declined after ovulation. BMP15 was able to activate Smad1 (mothers against decapentaplegichomolog1) signaling pathway in hen GCs. Moreover, we showed a strong inhibitory effect of BMP15 on gonadotropin-induced progesterone production in hen GCs. This inhibitory effect was associated with a decrease in steroidogenic acute regulatory protein (STAR) level. Taken together, our results suggest that BMP15 may have a key role in the female fertility of birds.Journal of Endocrinology 10/2007; 194(3):485-97. · 3.55 Impact Factor -
Article: Peroxisome proliferator-activated receptors in reproductive tissues: from gametogenesis to parturition.
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ABSTRACT: Peroxisome proliferator-activated receptors (PPARalpha, PPARbeta/delta and PPARgamma) are a family of nuclear receptors that are activated by binding of natural ligands, such as polyunsaturated fatty acids or by synthetic ligands. Synthetic molecules of the glitazone family, which bind to PPARgamma, are currently used to treat type II diabetes and also to attenuate the secondary clinical symptoms frequently associated with insulin resistance, including polycystic ovary syndrome (PCOS). PPARs are expressed in different compartments of the reproductive system (hypothalamus, pituitary, ovary, uterus and testis). Conservative functions of PPARs in mammalian species could be suggested through several in vivo and in vitro studies, especially in the ovary and during placental development. Several groups have described a strong expression of PPARgamma in ovarian granulosa cells, and glitazones modulate granulosa cell proliferation and steroidogenesis in vitro. All these recent data raise new questions about the biologic actions of PPARs in reproduction and their use in therapeutic treatments of fertility troubles such as PCOS or endometriosis. In this review, we first describe the roles of PPARs in different compartments of the reproductive axis (from male and female gametogenesis to parturition), with a focus on PPARgamma. Secondly, we discuss the possible molecular mechanisms underlying the effect of glitazones on PCOS. Like other 'insulin sensitizer' molecules, such as metformin, glitazones may in fact act directly on ovarian cells. Finally, we discuss the eventual actions of PPARs as mediators of environmental toxic substances for reproductive function.Journal of Endocrinology 06/2006; 189(2):199-209. · 3.55 Impact Factor -
Article: Molecular basis of bone morphogenetic protein-4 inhibitory action on progesterone secretion by ovine granulosa cells.
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ABSTRACT: We have recently reported that bone morphogenetic protein-4 (BMP-4) can inhibit progesterone production by ovine granulosa cells (GCs). Here, we have investigated the underlying mechanisms of this effect in basal as well as in FSH-induced conditions. We have confirmed that treatment with BMP-4 decreased basal GC progesterone secretion and totally abolished FSH-stimulating action. This inhibitory action was associated with a decrease in the expression of cAMP-regulated genes, steroidogenic acute regulatory protein (StAR) and P450 side-chain cleavage (P450 scc) at mRNA and protein levels. However, BMP-4 did not alter basal cAMP production by GCs. In contrast, BMP-4 decreased by half the FSH-induced cAMP production and strongly inhibited cAMP-induced progesterone production. Thus, the inhibitory effect of BMP-4 was exerted both upstream and downstream of cAMP signalling. We next examined the downstream effect, focusing on cAMP-dependent transcription factors, steroidogenic factor-1 (SF-1) and CREB, through the BMP factor signalling intermediary, Smad1. As expected, BMP-4 induced phosphorylation and transcriptional activity of Smad1 in ovine GCs. BMP-4-activated Smad1 did not affect CREB activity but inhibited the transcriptional activity of SF-1 on the canonical SF-1 responsive element. Interestingly, this transcriptional inhibitory mechanism occurred on transfected StAR and P450 scc promoter. Based on these results, we propose that SF-1 is a key target in the inhibitory mechanism exerted by BMP-4 on progesterone synthesis by ovine GCs in culture. Because SF-1 plays an essential role in the differentiation of GCs, our findings could have new implications in understanding the role of BMP family members in the control of ovarian folliculogenesis.Journal of Molecular Endocrinology 01/2005; 33(3):805-17. · 3.48 Impact Factor -
Article: Activin and inhibin receptor gene expression in the ewe pituitary throughout the oestrous cycle.
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ABSTRACT: In mammals, activin and inhibin are important regulators of FSH secretion. Previous studies have demonstrated that primary ovine pituitary cells express different activin receptor subtypes: activin receptor-like (ALK)2, ALK4, activin type II receptor A (ActRIIA), ActRIIB and Smad proteins in vitro. Here, we have carried out physiological studies to investigate the pattern of mRNA expression of the activin receptor subunits in the ewe pituitary throughout the oestrous cycle. The oestrous cycles of ewes were synchronized with progestagen sponges. The animals were killed 36 h (before the preovulatory surge, n=4), 48 h (during the preovulatory surge, n=4), 72 h (during the second surge of FSH, n=6) and 192 h (during the luteal phase, n=4) after sponge removal. Using Northern blots, we have shown that the levels of ALK2, ALK4 and ActRIIB mRNA were significantly higher before the preovulatory surge and during the secondary surge of FSH as compared with both during the preovulatory surge and the luteal phase, whereas the level of the ActRIIA mRNA was similar throughout the oestrous cycle. Using Western blots we have also demonstrated that the level of phospho-Smad2 did not vary during the reproductive cycle. Inhibin binding protein (InhBP/p120) and the transforming growth factor-beta type III receptor, betaglycan, have been identified as putative inhibin co-receptors. In this study, we cloned a fragment of both InhBP/p120 and betaglycan cDNAs in the ewe and showed by Northern blot that pituitary betaglycan and InhBP/p120 mRNA levels did not fluctuate across the oestrous cycle nor did they correlate with serum FSH levels.Journal of Endocrinology 08/2004; 182(1):55-68. · 3.55 Impact Factor -
Article: The insulin-like growth factor axis in cell cycle progression.
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ABSTRACT: Emerging evidence suggests that members of the Insulin-like Growth Factors (IGFs) family, including IGF-I, IGF-II, the IGF-I receptor (IGF-IR), and the IGF-binding proteins (IGFBPs) play a central role in the development and progression of cancer. Cancer cells exhibit an increased and deregulated proliferative activity. Abnormalities in many positive and negative modulators of the cell cycle are also frequent in many cancer types. Recent advances in the understanding of cell-cycle control mechanisms have been applied to outline the molecular mechanism through which IGFs regulate cell cycle progression. In this review, we will provide a brief overview of the role of the IGF system as a regulator of some components of the cell cycle.Hormone and Metabolic Research 35(11-12):740-50. · 2.19 Impact Factor
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Institutions
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2004–2010
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French National Institute for Agricultural Research
- Physiologie de la Reproduction et des Comportements (PRC)
Paris, Ile-de-France, France
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