References of "Bourguignon, Jean-Pierre p000716/"
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See detailGPR151, a new regulator of GnRH neurons
Franssen, Delphine ULiege; Lopez Rodriguez, David ULiege; Dupuis, Nadine et al

Poster (2019, September)

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See detailEffects of exposure to an EDC mixture on the pubertal timing through a maternal behavioral epigenetic multigenerational transmission
Lopez Rodriguez, David ULiege; Delli, Virginia; GERARD, Arlette ULiege et al

Conference (2019)

Endocrine disrupting chemicals (EDCs) are today a rising public health challenge because of their ubiquity and presence in complex mixtures and their effects on the developing body throughout generations ... [more ▼]

Endocrine disrupting chemicals (EDCs) are today a rising public health challenge because of their ubiquity and presence in complex mixtures and their effects on the developing body throughout generations. We aim at studying the effect of a mixture of EDCs on female sexual development during 3 generations of females after exposure and determine whether an epigenetic hypothalamic mechanism is involved in those effects. Female rats were orally exposed from 2 weeks before gestation until weaning to corn oil or a mixture of 14 anti-androgenic and estrogenic EDCs at low doses (F0 generation). Sexual development (vaginal opening, GnRH interpulse interval and estrous cyclicity) as well as maternal behavior were measured from F1 to F3 generation. An RNAseq was carry out using mediobasal hypothalamus from females at P21 from the F1 and F3 generation to decipher targets of the exposure, then validated by RT-PCR and studied for epigenetic modifications by ChIP. F2 and F3 females showed a delayed puberty (delayed VO) and a decrease in the percentage of females having regular estrous cycles, characterized by a significant increase in the time spent in estrus and decreased time spent in diestrus. A hypothalamic epigenetic mechanism is known to be involved in the onset of puberty. We have observed both transcriptional and histone epigenetic alterations in genes involved in estrogen (ESR1), glutamtergic (GRIN2Dà and dopamine (TH and DRD1) signaling as well as in glucocorticoid activity (NR3C1 and CRH), kisspeptin (KISS1) and oxytocin (OXT). We have as well observed that F1 females, exposed in utero, which shows a decrease in TH mRNA expression spent less time licking and more time resting alone. Those modifications on maternal behavior are known to be transmitted through generations. Overall, data shows that gestational exposure to an EDCs mixture can affect maternal behavior and sexual development during several generations. The F1 alteration of maternal behavior caused by in utero exposure to the mixture of EDCs trigger a multigenerational transmission of the phenotype and an induces an altered epigenetic reprogramming if the hypothalamus. [less ▲]

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See detailEDC mixture disrupts maternal behavior and the hypothalamic control of puberty transgenerationally through epigenetic mechanisms.
Lopez Rodriguez, David ULiege; Alwin, Carlos Francisco; GERARD, Arlette ULiege et al

Poster (2019)

Endocrine disrupting chemicals (EDCs) are a rising concern for public health due to their ubiquity as complex mixtures. Our goal was to study the effect of an EDC mixture on female sexual development ... [more ▼]

Endocrine disrupting chemicals (EDCs) are a rising concern for public health due to their ubiquity as complex mixtures. Our goal was to study the effect of an EDC mixture on female sexual development during 3 generations. Female rats (F0 generation) were orally exposed to a mixture of 13 anti-androgenic and estrogenic EDCs or corn oil for 2 weeks before gestation until weaning. The mixture was composed of plasticizers, fungicides/pesticides, UV filters, parabens and acetaminophen at doses representing human exposure. Sexual development (vaginal opening, GnRH interpulse-interval, estrous cyclicity and folliculogenesis) and maternal behavior were studied from F0 to F3 generations. At PND21, mediobasal hypothalamus of the F1 and F3 were removed for gene expression, histone modifications and DNA methylation analysis of target genes. F2 and F3 females showed delayed vaginal opening, decreased percentage of regular estrous cycle, decreased GnRH interpulse interval and altered late stage folliculogenesis. F1 and F2 females showed decreased maternal licking behavior while spending more time resting alone. The phenotype was associated with transcriptional and epigenetic alterations of hypothalamic genes involved in reproductive competence and behavior like kisspeptin (Kiss1), oxytocin (Oxt), estrogen (Esr1), glutamate (Grin2d), dopamine signaling (Th) as well as glucocorticoid activity (Nr3c1 and Crh). We have found alterations in repressive (H3K27me3, H3K9me3) or active (H3K4me3, H3K9ac) histone marks concomitant with transcriptional activity. Overall, gestational and lactational exposure to an environmentally relevant EDC mixture transgenerationally affects sexual development throughout epigenetic reprogramming of the hypothalamic control of puberty. Such effects could be mediated by alterations of maternal behavior. [less ▲]

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See detailTransgenerational effects of exposure to an EDC mixture on maternal behavior and sexual development
Lopez Rodriguez, David ULiege; Delli, Virginia; GERARD, Arlette ULiege et al

Conference (2018, July 17)

Environmental factors such as endocrine disrupting chemicals (EDCs) have been proven to produce transgenerational inherited modifications. A rising public health challenge is to determine the effect of ... [more ▼]

Environmental factors such as endocrine disrupting chemicals (EDCs) have been proven to produce transgenerational inherited modifications. A rising public health challenge is to determine the effect of complex mixtures of EDCs on the developing body throughout generations. In this study we aim to determine the transgenerational effects of a mixture of EDCs on female sexual development and behavior. Female rats were orally exposed from 2 weeks before gestation until weaning to corn oil or a mixture of 14 anti-androgenic and estrogenic EDCs at low doses. Sexual development (sex ratio, vaginal opening (VO), GnRH interpulse interval and estrous cyclicity) as well as maternal behavior were measured from F0 to F3 generation. In utero exposed females (F1) when raising pups, showed an increased time resting alone and decreased time licking and grooming pups. F2 (animals whose germlines were exposed) and F3 exposed animals showed an altered sex ratio in favor of males and F2 and F3 females showed delayed VO. F2 and F3 females followed for estrous cyclicity showed significant alterations of estrous cyclicity characterized by a significant increase in the time spent in estrus and decreased time spent in diestrus. F3 females presented an increased GnRH interpulse interval compared to control. Overall, data shows that gestational exposure to an EDCs mixture can affect maternal behavior and sexual development during several generations. The effects observed in the F3 generation suggest the presence of transgenerational epigenetic mechanisms. [less ▲]

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See detailA gestational exposure to EDCs induces transgenerational effects on maternal behavior and female sexual development
Lopez Rodriguez, David ULiege; Delli, Virginia; GERARD, Arlette ULiege et al

Conference (2018)

Environmental factors such as endocrine disrupting chemicals (EDCs) have been proven to involve transgenerational mechanisms in their effects. Environmentally relevant mixtures of EDCs pose a public ... [more ▼]

Environmental factors such as endocrine disrupting chemicals (EDCs) have been proven to involve transgenerational mechanisms in their effects. Environmentally relevant mixtures of EDCs pose a public health challenge and their effects on developmental endpoints throughout generations remain largely unknown. In this study we aim to determine the transgenerational effects of a mixture of EDCs on maternal behavior and female sexual development in the offspring. Female rats were orally exposed from 2 weeks before gestation until weaning to corn oil or a mixture of 14 anti-androgenic and/or estrogenic EDCs at low doses. Sexual development (sex ratio, vaginal opening (VO), pulsatile GnRH secretion from hypothalamic explants and estrous cyclicity) as well as maternal behavior were studied from F0 to F3 generation. When adult females exposed In utero (F1) were raising pups, they showed an increased time resting alone and a decreased time licking and grooming pups. In F2 (animals whose germlines were exposed) and F3 generations after exposure, an altered sex ratio was observed in favor of males and F2 and F3 females showed delayed VO. These sexually delayed F2 and F3 females subsequently showed significant alterations of estrous cyclicity characterized by a significant increase in the time spent in estrus and decreased time spent in diestrus. F3 females presented an increased GnRH interpulse interval compared to control. Overall, the data shows that gestational and lactational exposure to an EDCs mixture can affect maternal behavior in F1 generation and sexual development during several generations. The effects observed in the F3 generation suggest the involvement of indirect and possibly epigenetic mechanisms. [less ▲]

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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 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 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 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 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 detailPreface
Wit, J. M.; Sizonenko, P. C.; Bourguignon, Jean-Pierre ULiege et al

in Endocrine Development (2016), 29

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See detailExposure to endocrine-disrupting chemicals in the USA: a population-based disease burden and cost analysis
Attina, T. M.; Hauser, R.; Sathyanarayana, S. et al

in Lancet Diabetes and Endocrinology (2016), 4(12), 996-1003

Background Endocrine-disrupting chemicals (EDCs) contribute to disease and dysfunction and incur high associated costs (>1% of the gross domestic product [GDP] in the European Union). Exposure to EDCs ... [more ▼]

Background Endocrine-disrupting chemicals (EDCs) contribute to disease and dysfunction and incur high associated costs (>1% of the gross domestic product [GDP] in the European Union). Exposure to EDCs varies widely between the USA and Europe because of differences in regulations and, therefore, we aimed to quantify disease burdens and related economic costs to allow comparison. Methods We used existing models for assessing epidemiological and toxicological studies to reach consensus on probabilities of causation for 15 exposure–response relations between substances and disorders. We used Monte Carlo methods to produce realistic probability ranges for costs across the exposure–response relation, taking into account uncertainties. Estimates were made based on population and costs in the USA in 2010. Costs for the European Union were converted to US$ (€1=$1·33). Findings The disease costs of EDCs were much higher in the USA than in Europe ($340 billion [2·33% of GDP] vs $217 billion [1·28%]). The difference was driven mainly by intelligence quotient (IQ) points loss and intellectual disability due to polybrominated diphenyl ethers (11 million IQ points lost and 43 000 cases costing $266 billion in the USA vs 873 000 IQ points lost and 3290 cases costing $12·6 billion in the European Union). Accounting for probability of causation, in the European Union, organophosphate pesticides were the largest contributor to costs associated with EDC exposure ($121 billion), whereas in the USA costs due to pesticides were much lower ($42 billion). Interpretation EDC exposure in the USA contributes to disease and dysfunction, with annual costs taking up more than 2% of the GDP. Differences from the European Union suggest the need for improved screening for chemical disruption to endocrine systems and proactive prevention. Funding Endocrine Society, Ralph S French Charitable Foundation, and Broad Reach Foundation. © 2016 Elsevier Ltd [less ▲]

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See detailScientific issues relevant to setting regulatory criteria to identify endocrine-disrupting substances in the european union
Slama, R.; Bourguignon, Jean-Pierre ULiege; Demeneix, B. et al

in Environmental Health Perspectives (2016), 124(10), 1497-1503

Endocrine disruptors (EDs) are defined by the World Health Organization (WHO) as exogenous compounds or mixtures that alter function(s) of the endocrine system and consequently cause adverse effects in an ... [more ▼]

Endocrine disruptors (EDs) are defined by the World Health Organization (WHO) as exogenous compounds or mixtures that alter function(s) of the endocrine system and consequently cause adverse effects in an intact organism, or its progeny, or (sub)populations. European regulations on pesticides, biocides, cosmetics, and industrial chemicals require the European Commission to establish scientific criteria to define EDs. Objectives: We address the scientific relevance of four options for the identification of EDs proposed by the European Commission. [less ▲]

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See detailEU regulation of endocrine disruptors: a missed opportunity
Kortenkamp, A.; Bourguignon, Jean-Pierre ULiege; Slama, R. et al

in Lancet Diabetes and Endocrinology (2016), 4(8), 649-650

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See detailPeer-reviewed and unbiased research, rather than 'sound science', should be used to evaluate endocrine-disrupting chemicals
Trasande, L.; Vandenberg, L. N.; Bourguignon, Jean-Pierre ULiege et al

in Journal of Epidemiology and Community Health (2016), 70(11), 1051-1056

Evidence increasingly confirms that synthetic chemicals disrupt the endocrine system and contribute to disease and disability across the lifespan. Despite a United Nations Environment Programme/WHO report ... [more ▼]

Evidence increasingly confirms that synthetic chemicals disrupt the endocrine system and contribute to disease and disability across the lifespan. Despite a United Nations Environment Programme/WHO report affirmed by over 100 countries at the Fourth International Conference on Chemicals Management, 'manufactured doubt' continues to be cast as a cloud over rigorous, peer-reviewed and independently funded scientific data. This study describes the sources of doubt and their social costs, and suggested courses of action by policymakers to prevent disease and disability. The problem is largely based on the available data, which are all too limited. Rigorous testing programmes should not simply focus on oestrogen, androgen and thyroid. Tests should have proper statistical power. 'Good laboratory practice' (GLP) hardly represents a proper or even gold standard for laboratory studies of endocrine disruption. Studies should be evaluated with regard to the contamination of negative controls, responsiveness to positive controls and dissection techniques. Flaws in many GLP studies have been identified, yet regulatory agencies rely on these flawed studies. Peer-reviewed and unbiased research, rather than 'sound science', should be used to evaluate endocrine-disrupting chemicals. [less ▲]

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