References of "Parent, Anne-Simone"
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See detailActivation of the orphan G protein-coupled receptor GPR27 by surrogate ligands promotes β-arrestin 2 recruitment
Dupuis, Nadine ULg; Laschet, Céline ULg; Franssen, Delphine ULg et al

in Molecular Pharmacology (in press)

G protein-coupled receptors are the most important drug targets for human diseases. An important number of them remain devoid of confirmed ligands. GPR27 is one of these orphan receptors, characterized by ... [more ▼]

G protein-coupled receptors are the most important drug targets for human diseases. An important number of them remain devoid of confirmed ligands. GPR27 is one of these orphan receptors, characterized by a high level of conservation among vertebrates and a predominant expression in the central nervous system. In addition, it has recently been linked to insulin secretion. However, the absence of endogenous or surrogate ligands for GPR27 complicates the examination of its biological function. Our aim was to validate GPR27 signaling pathways and therefore we sought to screen a diversity oriented synthesis library to identify GPR27-specific surrogate agonists. In order to select an optimal screening assay, we investigated GPR27 ligand-independent activity. Both in G protein-mediated pathways and in β-arrestin 2 recruitment, no ligand-independent activity could be measured. However, we observed a recruitment of β-arrestin 2 to a GPR27V2 chimera in the presence of membrane-anchored β-adrenergic receptor kinase 1 (GRK2). Therefore, we optimized a firefly luciferase complementation assay to screen against this chimeric receptor. We identified two compounds (N-[4-(anilinocarbonyl)phenyl]-2,4-dichlorobenzamide (ChemBridge ID5128535) and 2,4-dichloro-N-{4-[(1,3-thiazol-2-ylamino)sulfonyl]phenyl}benzamide (ChemBridge ID5217941)) sharing a N-phenyl-2,4-dichlorobenzamide scaffold, which were selective for GPR27 over its closely related family members GPR85 and GPR173. The specificity of the activity was confirmed with a NanoBiT® β-arrestin 2 assay, imaging of GFP-tagged β-arrestin 2 and PathHunter® β-arrestin 2 Assay. Interestingly, no G protein activation was detected upon activation of GPR27 by these compounds. Our study provides the first selective surrogate agonists for the orphan GPR27. [less ▲]

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See detailEarly exposure to Aroclor 1254 in vivo disrupts the functional synaptic development of newborn hippocampal granule cells.
Parent, Anne-Simone ULg; Pinson, Anneline ULg; Woods, N. et al

in European Journal of Neuroscience (2016), 44(12), 3001-3010

Neurogenesis in the dentate gyrus is sensitive to endogenous and exogenous factors that influence hippocampal function. Ongoing neurogenesis and the integration of these new neurons throughout life thus ... [more ▼]

Neurogenesis in the dentate gyrus is sensitive to endogenous and exogenous factors that influence hippocampal function. Ongoing neurogenesis and the integration of these new neurons throughout life thus may provide a sensitive indicator of environmental stress. We examined the effects of Aroclor 1254 (A1254), a mixture of polychlorinated biphenyls (PCBs), on the development and function of newly generated dentate granule cells. Early exposure to A1254 has been associated with learning impairment in children, suggesting potential impact on the development of hippocampus and/or cortical circuits. Oral A1254 (from the 6th day of gestation to postnatal day 21) produced the expected increase in PCB levels in brain at postnatal day 21, which persisted at lower levels into adulthood. A1254 did not affect the proliferation or survival of newborn neurons in immature animals nor did it cause overt changes in neuronal morphology. However, A1254 occluded the normal developmental increase in sEPSC frequency in the third post-mitotic week without altering the average sEPSC amplitude. Our results suggest that early exposure to PCBs can disrupt excitatory synaptic function during a period of active synaptogenesis, and thus could contribute to the cognitive effects noted in children exposed to PCBs. [less ▲]

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See detailValidation of Prediction Models for Near Adult Height in Children with Idiopathic Growth Hormone Deficiency Treated with Growth Hormone A Belgian Registry Study
Straetemans, Saartje; De Schepper, Jean; THOMAS, Muriel et al

in Hormone Research in Paediatrics (2016), 86

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See detailLoss of oocytes due to conditional ablation of Murine double minute 2 (Mdm2) gene is p53-dependent and results in female sterility.
Livera, Gabriel; Uzbekov, Rustem; Jarrier, Peggy et al

in FEBS Letters (2016), 590(16), 2566-74

Murine double minute 2 and 4 (Mdm2, Mdm4) are major p53-negative regulators, preventing thus uncontrolled apoptosis induction in numerous cell types, although their function in the female germ line has ... [more ▼]

Murine double minute 2 and 4 (Mdm2, Mdm4) are major p53-negative regulators, preventing thus uncontrolled apoptosis induction in numerous cell types, although their function in the female germ line has received little attention. In the present work, we have generated mice with specific invalidation of Mdm2 and Mdm4 genes in the mouse oocyte (Mdm2(Ocko) and Mdm4(Ocko) mice), to test their implication in survival of these germ cells. Most of the Mdm2(Ocko) but not Mdm4(Ocko) mice were sterile, with a dramatic reduction of the weight of ovaries and genital tract, a strong increase in follicle-stimulating hormone and luteinizing hormone serum levels, and a reduction of anti-mullerian hormone serum levels. Histological analyses revealed an obvious decrease of the number of growing follicles beyond the primary stage in Mdm2(Ocko) ovaries in comparison to controls, with a pronounced increase in the apparition of primary atretic follicles, most being devoid of oocyte. Similar phenotypes were observed with Mdm2(Ocko) Mdm4(Ocko) ovaries, with no worsening of the phenotype. However, we failed to detect any increase in p53 level in mutant oocytes, nor any other apoptotic marker, introgression of this targeted invalidation in p53-/- mice restored the fertility of females. This study is the first to show that Mdm2, but not Mdm4, has a critical role in oocyte survival and would be involved in premature ovarian insufficiency phenotype. [less ▲]

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See detailExposure to endocrine disrupting chemicals and neurodevelopmental alterations.
Pinson, Anneline ULg; Bourguignon, Jean-Pierre ULg; Parent, Anne-Simone ULg

in Andrology (2016), 4(4), 706-22

The developing brain is remarkably malleable as neural circuits are formed and these circuits are strongly dependent on hormones for their development. For those reasons, the brain is very vulnerable to ... [more ▼]

The developing brain is remarkably malleable as neural circuits are formed and these circuits are strongly dependent on hormones for their development. For those reasons, the brain is very vulnerable to the effects of endocrine-disrupting chemicals (EDCs) during critical periods of development. This review focuses on three ubiquitous endocrine disruptors that are known to disrupt the thyroid function and are associated with neurobehavioral deficits: polychlorinated biphenyls, polybrominated diphenyl ethers, and bisphenol A. The human and rodent data suggesting effects of those EDCs on memory, cognition, and social behavior are discussed. Their mechanisms of action go beyond relative hypothyroidism with effects on neurotransmitter release and calcium signaling. [less ▲]

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See detailNovel composite heterozygous mutation of the receptor for hCG and LH leading to male disorder of sexual development
Potorac, Iulia ULg; FUDVOYE, Julie ULg; GAILLEZ, Stephanie ULg et al

in Abstract book - 17th World Congress of Gynecological Endocrinology (2016, March)

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See detailPuberty from bench to clinic
Bourguignon, Jean-Pierre ULg; Parent, Anne-Simone ULg

Book published by Karger (2016)

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See detailDelayed neuroendocrine sexual maturation in female rats after a very low dose of Bisphenol A through altered GABAergic neurotransmission and opposing effects of a high dose.
Franssen, Delphine ULg; GERARD, Arlette ULg; HENNUY, Benoit ULg et al

in Endocrinology (2016)

Rat sexual maturation is preceded by a reduction of the interpulse interval (IPI) of gonadotropinreleasing hormone (GnRH) neurosecretion. This work aims at studying disruption of that neuroendocrine event ... [more ▼]

Rat sexual maturation is preceded by a reduction of the interpulse interval (IPI) of gonadotropinreleasing hormone (GnRH) neurosecretion. This work aims at studying disruption of that neuroendocrine event in females after early exposure to a very low dose of Bisphenol A (BPA), a ubiquitous endocrine disrupting chemical. Female rats were exposed to vehicle or BPA 25 ng/kg.day, 25 g/kg.day, or 5 mg/kg.day from postnatal day (PND) 1 to 5 or 15. Exposure to 25 ng/kg.day of BPA for 5 or 15 days was followed by a delay in developmental reduction of GnRH IPI studied ex vivo on PND 20. After 15 days of exposure to that low dose of BPA, vaginal opening tended to be delayed. In contrast, exposure to BPA 5 mg/kg.day for 15 days resulted in a premature reduction inGnRHIPI and a trend toward early vaginal opening. RNAseq analysis on PND20 indicated that exposure to BPA resulted in opposing dose effectsonthemRNAexpression of hypothalamic genes involved inGABAA neurotransmission. The study of GnRH secretion in vitro in the presence of GABAA receptor agonist/antagonist confirmed an increased or a reduced GABAergic tone after in vivo exposure to the very low or the high dose of BPA, respectively. Overall, we show for the first time that neonatal exposure to BPA leads to opposing dose-dependent effects on the neuroendocrine control of puberty in the female rat. A very low and environmentally relevant dose of BPA delays neuroendocrine maturation related to puberty through increased inhibitory GABAergic neurotransmission. [less ▲]

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See detailApoptosis of Sertoli cells after conditional ablation of murine double minute 2 (Mdm2) gene is p53-dependent and results in male sterility.
Fouchecourt, S.; Livera, G.; Messiaen, S. et al

in Cell death and differentiation (2016)

Beside its well-documented role in carcinogenesis, the function of p53 family has been more recently revealed in development and female reproduction, but it is still poorly documented in male reproduction ... [more ▼]

Beside its well-documented role in carcinogenesis, the function of p53 family has been more recently revealed in development and female reproduction, but it is still poorly documented in male reproduction. We specifically tested this possibility by ablating Mdm2, an E3 ligase that regulates p53 protein stability and transactivation function, specifically in Sertoli cells (SCs) using the AMH-Cre line and created the new SC-Mdm2-/- line. Heterozygous SC-Mdm2-/+ adult males were fertile, but SC-Mdm2-/- males were infertile and exhibited: a shorter ano-genital distance, an extra duct along the vas deferens that presents a uterus-like morphology, degenerated testes with no organized seminiferous tubules and a complete loss of differentiated germ cells. In adults, testosterone levels as well as StAR, P450c17 (Cyp17a1) and P450scc (Cyp11a1) mRNA levels decreased significantly, and both plasma LH and FSH levels increased. A detailed investigation of testicular development indicated that the phenotype arose during fetal life, with SC-Mdm2-/- testes being much smaller at birth. Interestingly, Leydig cells remained present until adulthood and fetal germ cells abnormally initiated meiosis. Inactivation of Mdm2 in SCs triggered p53 activation and apoptosis as early as 15.5 days post conception with significant increase in apoptotic SCs. Importantly, testis development occurred normally in SC-Mdm2-/- lacking p53 mice (SC-Mdm2-/-p53-/-) and accordingly, these mice were fertile indicating that the aforementioned phenotypes are entirely p53-dependent. These data not only highlight the importance of keeping p53 in check for proper testicular development and male fertility but also certify the critical role of SCs in the maintenance of meiotic repression.Cell Death and Differentiation advance online publication, 16 October 2015; doi:10.1038/cdd.2015.120. [less ▲]

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See detailCurrent Changes in Pubertal Timing: Revised Vision in Relation with Environmental Factors Including Endocrine Disruptors.
Parent, Anne-Simone ULg; Franssen, Delphine ULg; Fudvoye, Julie ULg et al

in Endocrine development (2016), 29

The aim of this chapter is to revise some common views on changes in pubertal timing. This revision is based on recent epidemiological findings on the clinical indicators of pubertal timing and data on ... [more ▼]

The aim of this chapter is to revise some common views on changes in pubertal timing. This revision is based on recent epidemiological findings on the clinical indicators of pubertal timing and data on environmental factor effects and underlying mechanisms. A current advancement in timing of female puberty is usually emphasized. It appears, however, that timing is also changing in males. Moreover, the changes are towards earliness for initial pubertal stages and towards lateness for final stages in both sexes. Such observations indicate the complexity of environmental influences on pubertal timing. The mechanisms of changes in pubertal timing may involve both the central neuroendocrine control and peripheral effects at tissues targeted by gonadal steroids. While sufficient energy availability is a clue to the mechanism of pubertal development, changes in the control of both energy balance and reproduction may vary under the influence of common determinants such as endocrine-disrupting chemicals (EDCs). These effects can take place right before puberty as well as much earlier, during fetal and neonatal life. Finally, environmental factors can interact with genetic factors in determining changes in pubertal timing. Therefore, the variance in pubertal timing is no longer to be considered under absolutely separate control by environmental and genetic determinants. Some recommendations are provided for evaluation of EDC impact in the management of pubertal disorders and for possible reduction of EDC exposure along the precautionary principle. [less ▲]

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See detailA novel mutation of the luteinizing hormone/choionic gonadotrophin receptor gene leading to Leydig cell hypoplasia type I
Potorac, Iulia ULg; Rivero-Muller, A; Pintiaux, Axelle ULg et al

in The International Journal of The Romania Society of Endocrinology - Abstract book (2015, June)

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See detailThe effects of perinatal exposure to polychlorinated biphenyls on hippocampal neurogenesis
Pinson, Anneline ULg; Parent, Anne-Simone ULg; chatzi, christina et al

Poster (2015, May)

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