References of "Parent, Anne-Simone"
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See detailNeuroendocrine disruption without direct endocrine mode of action: Polychloro-biphenyls (PCBs) and bisphenol A (BPA) as case studies
Pinson, Anneline ULiege; Franssen, Delphine ULiege; Gerard, Amaury ULiege et al

in Comptes Rendus Biologies (2017), 340(9-10), 432-438

Endocrine disruption is commonly thought to be restricted to a direct endocrine mode of action i.e. the perturbation of the activation of a given type of hormonal receptor by its natural ligand ... [more ▼]

Endocrine disruption is commonly thought to be restricted to a direct endocrine mode of action i.e. the perturbation of the activation of a given type of hormonal receptor by its natural ligand. Consistent with the WHO definition of an endocrine disrupter, a key issue is the “altered function(s) of the endocrine system”. Such altered functions can result from different chemical interactions, beyond agonistic or antagonistic effect at a given receptor. Based on neuroendocrine disruption by polychlorinated biphenyls and bisphenol A, this paper proposes different mechanistic paradigms that can result in adverse health effects. They are a consequence of altered endocrine function(s) secondary to chemical interaction with different steps in the physiological regulatory processes, thus accounting for a possibly indirect endocrine mode of action. © 2017 Académie des sciences [less ▲]

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

in Molecular Pharmacology (2017), 91(6), 595-608

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 detailSecular trends in growth.
FUDVOYE, Julie ULiege; Parent, Anne-Simone ULiege

in Annales d'Endocrinologie (2017), 78(2), 88-91

Human adult height has been increasing world-wide for a century and a half. The rate of increase depends on time and place of measurement. Final height appears to have reached a plateau in Northern ... [more ▼]

Human adult height has been increasing world-wide for a century and a half. The rate of increase depends on time and place of measurement. Final height appears to have reached a plateau in Northern European countries but it is still increasing in southern European countries as well as Japan. While mean birth length has not changed recently in industrialized countries, the secular trend finally observed in adult height mostly originates during the first 2 years of life. Secular trend in growth is a marker of public health and provides insights into the interaction between growth and environment. It has been shown to be affected by income, social status, infections and nutrition. While genetic factors cannot explain such rapid changes in average population height, epigenetic factors could be the link between growth and environment. [less ▲]

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See detailActivational and organizational disruption of folliculogenesis and estrous cycle caused by exposure to Bisphenol A (BPA) during early postnatal or adult life
Lopez Rodriguez, David ULiege; Franssen, Delphine ULiege; GERARD, Arlette ULiege et al

Conference (2017, May 05)

Our previous studies have shown that an early postnatal exposure to a very low dose of bisphenol A (BPA) disrupts sexual maturation and pubertal timing. However, the long-term effects of such low dose ... [more ▼]

Our previous studies have shown that an early postnatal exposure to a very low dose of bisphenol A (BPA) disrupts sexual maturation and pubertal timing. However, the long-term effects of such low dose exposure as well as the effects of adult exposure have not been studied. One day-old and 90 day-old female rats received daily subcutaneous injections of corn oil (vehicle) or BPA (25ng/kg/d or 5mg/kg/d) for 15 days. The early postnatal exposure to both BPA doses significantly decreased the percentage of females with a regular cycle (BPA-25ng: 51±15%; BPA-5mg: 7±7%; OIL: 86±2%). The estrus cycle alterations were characterized by a decrease in time spent in proestrus (BPA-25ng: 13±3%; BPA-5mg: 12±3%; OIL: 18±3%). During adult exposure, both doses caused a disruption of the estrous cycle characterized by a significant decrease in the average time spent in proestrus (BPA-25ng: 19±2%; BPA-5mg: 17±1%; OIL: 23±1%). This effect was transient as the exposed females showed a regular cycle one month after the last dose of BPA. After adult exposure, we also observed a disruption of folliculogenesis characterized by a significant decrease of antral follicles (BPA-25ng: 21±2%; BPA-5mg: 21±2%; OIL: 36±2%) and increase of atretic follicles (BPA-25ng: 24±4%; BPA-5mg: 26±6%; OIL: 15±1%). GnRH secretion measured ex vivo 24h after adult exposure was moderately affected by BPA. Indeed, GnRH interpulse interval was significantly different when comparing animals exposed to the high or low dose of BPA but not when comparingexposed animals to the control group (BPA-25ng: 42.6±0.5; BPA-5mg: 40.2±0.6%; OIL: 41.1±0,2minutes±SEM). In conclusion, while exposure to BPA produces persistent alterations of the estrous cycle after early postnatal exposure, exposure during adulthood appears to cause activational non-persistent alternations of both the estrous cycle and folliculogenesis. [less ▲]

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See detailLow/medium doses of inhaled corticosteroids can cause adrenal insufficiency
FUDVOYE, Julie ULiege; LEBRETHON, Marie-Christine ULiege; Parent, Anne-Simone ULiege

in Belgian Journal of Paediatrics (2017, March), 19(1),

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See detailSeptal hypertrophy and myocardial cell damage in a neonate born from a mother with pregestational diabetis
Zambelli, Laura ULiege; Balthasar, Virginie ULiege; FARHAT, Nesrine ULiege et al

in Belgian Journal of Paediatrics (2017, March), 19(1), 30

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See detailEarly postnatal and adult exposure to BPA: activational vs organizational disruption of folliculogenesis and estrous cycle
Lopez Rodriguez, David ULiege; Franssen, Delphine ULiege; GERARD, Arlette ULiege et al

Conference (2017)

Aim: Our society is facing a public health problem linked to the production of endocrine disrupting chemicals (EDCs) (1). In our laboratory we have shown that an early postnatal exposure to a very low ... [more ▼]

Aim: Our society is facing a public health problem linked to the production of endocrine disrupting chemicals (EDCs) (1). In our laboratory we have shown that an early postnatal exposure to a very low dose of bisphenol A (BPA) disrupts sexual maturation and pubertal timing (2). However, the long-term and adult effects of such low doses have not been studied. Methods: one day-old and 90 day-old female rats received daily subcutaneous injections of corn oil (vehicle) or BPA (25ng/kg/day or 5mg/kg/day) for 15 days. For early postnatal exposure, estrous cyclicity was followed until P105 when folliculogenesis was studied. For adult exposure, estrous cyclicity was followed from two weeks before to four weeks after the exposure. Folliculogenesis was studied both 24h and 30 days after the adult BPA exposure. GnRH frequency was measure 24h after the adult BPA exposure. Results: early postnatal exposure to both BPA doses significantly decreased the percentage of females with a regular cycle (BPA-25ng: 51±15%; BPA-5mg: 7±7%; OIL: 86±2%). Folliculogenesis showed a significant decrease in the number of primordial follicles (BPA-25ng: 15.5±3.6; BPA-5mg: 20.4±5.2; OIL: 71.2±14.1) as well as a disruption in atretic follicles (BPA-25ng: 26.5±3.9; BPA-5mg: 111.9±29.4; OIL: 48.8±10.3) and the presence of cysts follicles (BPA-25ng: 0.04±0.02; BPA-5mg: 0.3±0.1). Adult exposure to BPA caused a disruption of the estrous cycle characterized by a significant decrease in the average time spent in proestrus (BPA-25ng: 19±2%; BPA-5mg: 17±1%; OIL: 23±1%). We also observed a disruption of folliculogenesis characterized by a significant decrease of antral follicles (BPA-25ng: 0.4±0.1; BPA-5mg: 0.5±0.07; OIL: 1.54±0.2), an increase of atretic follicles (BPA-25ng: 50.8±7.7; BPA-5mg: 48.7±6.7; OIL: 31.3±5.4) and the presence of cysts follicles (BPA-25ng: 0.2±0.1; BPA-5mg: 0.06±0.02). This effect was transient as the exposed females showed a regular cycle and folliculogenesis one month after the last dose of BPA. GnRH interpulse interval was significantly different when comparing animals exposed to the high or low dose of BPA but not when compared to the control group (BPA-25ng: 42.6±0.5; BPA-5mg: 40.2±0.6%; OIL: 41.1±0,2minutes±SEM). Conclusion: both early postnatal and adult exposure to BPA disrupts the estrous cycle and folliculogenesis. However, while adult exposure produces persistent alterations, the adult exposure cause activational effects. [less ▲]

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See detailLa déficience en FSH : actualités cliniques et thérapeutiques
VALDES SOCIN, Hernan Gonzalo ULiege; Pintiaux, Axelle ULiege; Delbaere, Anne et al

in Urologic (2017), 13(3), 16-22

L'hormone lutéinisante (LH) et l'hormone folliculostimulante (FSH) - hormones glycoprotéiques hypophysaires - régulent de concert la production de stéroïdes sexuels et la reproduction. Les stéroïdes ... [more ▼]

L'hormone lutéinisante (LH) et l'hormone folliculostimulante (FSH) - hormones glycoprotéiques hypophysaires - régulent de concert la production de stéroïdes sexuels et la reproduction. Les stéroïdes sexuels sont indispensables à la virilisation et à la féminisation, et participent également à la gamétogenèse (spermatogenèse chez l'homme et folliculogenèse chez la femme). Cet article sur le déficit en FSH fait suite à un article précédent publié dans Urologic décrivant le déficit en LH et ses conséquences sur la reproduction. [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 ULiege; Pinson, Anneline ULiege; 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 ULiege; Bourguignon, Jean-Pierre ULiege; Parent, Anne-Simone ULiege

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 ULiege; FUDVOYE, Julie ULiege; GAILLEZ, Stephanie ULiege et al

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

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See detailAdult exposure to BPA causes activational disruption of estrous cycle and folliculogenesis
Lopez Rodriguez, David ULiege; Franssen, Delphine ULiege; GERARD, Arlette ULiege et al

Conference (2016)

Our society is facing a public health challenge caused by the increasing presence of endocrine disrupting chemicals (EDCs). Bisphenol A (BPA) is a widespread EDC used in the manufacture of PVC and epoxy ... [more ▼]

Our society is facing a public health challenge caused by the increasing presence of endocrine disrupting chemicals (EDCs). Bisphenol A (BPA) is a widespread EDC used in the manufacture of PVC and epoxy resins. While early postnatal exposure to BPA disrupts sexual maturation andpubertal timing, , its effects on fertility after adult exposure have not yet been studied. Female Wistar rats were exposed for 15 days to corn oil or a low (25ng/kg/d) or a high (5mg/kg/d) BPA dose subcutateouslyat 90 days of age. Animals exposed to both doses showed a disruption of the estrous cyclicity characterized by a decrease in the average time spent in proestrus. We observed a disruption on folliculogenesis characterized by a significant decrease of antral follicles and increase of atretic follicles. The exposed females showed a regular cycle one month after the last dose of BPAWe did not observe any difference in the frequency or amplitude of GnRH secretion 24h after the end of exposure. We also observed that early postnatal exposure to BPA for 15 days disrupted estrous cycle during adulthood with a decrease in time spent in proestrus. In conclusion, exposure to BPA neonatally or during adulthood disrupts the estrous cycle and folliculogenesis. The effects of exposure to BPA during adulthood might be independent of GnRH secretion. Moreover, the effects of early postnatal exposure to BPA are persistent while exposure to BPA during adulthood appears to causeeactivational, non persistent alteration of the oestrus cycle. [less ▲]

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See detailActivational and organizational disruption of folliculogenesis and estrous cycle after an exposure to Bisphenol A (BPA) during early postnatal or adult window of exposure
Lopez Rodriguez, David ULiege; Franssen, Delphine ULiege; GERARD, Arlette ULiege et al

Poster (2016)

The increasing presence of endocrine disruption chemicals (EDCs) has been link with a reduction in fertility rate and alterations of pubertal timing. Bisphenol A (BPA) is a ubiquitous EDC used in the ... [more ▼]

The increasing presence of endocrine disruption chemicals (EDCs) has been link with a reduction in fertility rate and alterations of pubertal timing. Bisphenol A (BPA) is a ubiquitous EDC used in the manufacture of polyvinyl chloride (PVC) and epoxy resins that we can find in food containers and plastics. Our previous studies have shown that an early postnatal exposure to a low dose of BPA disrupts sexual maturation and pubertal timing. However, its long-term and adult effects on fertility have not yet been studied. Daily s.c injections of BPA were administered for 15 days to 1 and 90 day-old female Wistar rats at two different doses: a low dose of 25ng/kg/d and a high dose of 5mg/kg/d. The early postnatal exposure to both BPA doses produces a decrease in the percentage of female with a regular cycle characterized by a decrease on the time spend in proestrus (BPA-25ng 13,6±3,4; BPA-5mg 12,2±3,1%; OIL 18,7±3,2%). During exposure at adulthood, both doses caused a disruption of the estrous cycle characterized by a significant decrease in the average time spent in proestrus (BPA-25ng 18,9±2,2%; BPA-5mg 16,9±1,3%; OIL 23,3±0,9%). This effect was We also observed a disruption of folliculogenesis characterized by a significant decrease of antral follicles (BPA-25ng 21,4±2.1%; BPA-5mg 20,94±2%; OIL 35,6±1,6%) and increase of atretic follicles (BPA-25ng 24,2±3,9%; BPA-5mg 26,2±6,3%; OIL 15,5±0,8%). The exposed females showed a regular cycle one month after the last dose of BPA. In conclusion, both BPA doses have been found to produce a disruption of oestrus cycle and folliculogenesis depending on the window of exposure. While BPA produces persistent effects after early postnatal exposure, exposure during adulthood appears to cause activational, non-persistent alterations. [less ▲]

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

Book published by Karger (2016)

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