References of "Gerard, Arlette"
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See detailRight Atrial Myocardial Remodeling in Children With Atrial Septal Defect Involves Inflammation, Growth, Fibrosis, and Apoptosis.
Rouatbi, Hatem; FARHAT, Nesrine ULiege; Heying, Ruth et al

in Frontiers in pediatrics (2020), 8

Introduction: Myocardial remodeling due to large atrial septum defect (ASD) is macroscopically characterized by dilation of the right-sided cardiac cavities secondary to volume overload, the cellular ... [more ▼]

Introduction: Myocardial remodeling due to large atrial septum defect (ASD) is macroscopically characterized by dilation of the right-sided cardiac cavities secondary to volume overload, the cellular mechanisms of which are not yet understood. We postulated that inflammation, fibrosis, and cell death are actors of right atrial remodeling secondary to ASD. Patients and Methods: In 12 children with large ASD (median age: 63 months), expression of genes coding for proteins involved in the response to cell stress and -protection, inflammation, growth and angiogenesis, fibrosis, and apoptosis was assessed by RT-PCR in right atrial myocardial biopsies taken during cardiac surgery. The presence of cytokines in myocardial cells was confirmed by immunohistochemistry and effective apoptosis by TUNEL assay. Results: In all patients investigated, a cellular response to early mechanical stress with the initiation of early protective mechanisms, of inflammation (and its control), -growth, and -angiogenesis, of fibrosis and apoptosis was present. The apoptotic index assessed by TUNEL assay averaged 0.3%. Conclusions: In children with large ASD, macroscopic right atrial remodeling relates to cellular mechanisms involving the expression of numerous genes that either still act to protect cells and tissues but that also harm as they initiate and/or sustain inflammation, fibrosis, and cell death by apoptosis. This may contribute to long term morbidity in patients with ASD. [less ▲]

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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; Awylyn, Carlos Francisco; Sevrin, Elena ULiege et al

Conference (2019)

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See detailPersistent vs Transient Alteration of Folliculogenesis and Estrous Cycle After Neonatal vs Adult Exposure to Bisphenol A.
Lopez Rodriguez, David ULiege; Franssen, Delphine ULiege; Sevrin, Elena ULiege et al

in Endocrinology (2019), 160(11), 2558-2572

Exposure to bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical (EDC), is known to produce variable effects on female puberty and ovulation. This variability of effects is possibly due to ... [more ▼]

Exposure to bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical (EDC), is known to produce variable effects on female puberty and ovulation. This variability of effects is possibly due to differences in dose and period of exposure. Little is known about the effects of adult exposure to environmentally relevant doses of this EDC and the differences in effect after neonatal exposure. This study sought to compare the effects of neonatal vs adult exposure to a very low dose or a high dose of BPA for 2 weeks on ovulation and folliculogenesis and to explore the hypothalamic mechanisms involved in such disruption by BPA. One-day-old and 90-day-old female rats received daily subcutaneous injections of corn oil (vehicle) or BPA (25 ng/kg/d or 5 mg/kg/d) for 15 days. Neonatal exposure to both BPA doses significantly disrupted the estrous cycle and induced a decrease in primordial follicles. Effects on estrous cyclicity and folliculogenesis persisted into adulthood, consistent with a disruption of organizational mechanisms. During adult exposure, both doses caused a reversible decrease in antral follicles and corpora lutea. A reversible disruption of the estrous cycle associated with a delay and a decrease in the amplitude of the LH surge was also observed. Alterations of the hypothalamic expression of the clock gene Per1 and the reproductive peptide phoenixin indicated a disruption of the hypothalamic control of the preovulatory LH surge by BPA. [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 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 detailEFFECT OF ESTETROL ON THE NEGATIVE FEEDBACK OF ESTROGENS ON LH SECRETION
Khbouz, Badr ULiege; Corona, Rebeca; Gerard, Arlette ULiege et al

Poster (2017, May)

Estradiol (E2) is a key regulator of reproduction through its role on the feedback control of gonadotropin secretion by the hypothalamus. E2 effects are mainly mediated via estrogen receptor alpha (ERα ... [more ▼]

Estradiol (E2) is a key regulator of reproduction through its role on the feedback control of gonadotropin secretion by the hypothalamus. E2 effects are mainly mediated via estrogen receptor alpha (ERα) activation by a combination of the nuclear and the membrane-associated pathways. However, the contribution of these mechanisms to the regulation of reproduction is not completely clear. To elucidate this contribution, we used estetrol (E4), a human natural estrogen produced in human at late pregnancy which preferentially binds ERα and in peripheral tissuesacts as an agonist on the nuclear fraction of the receptor but as an antagonist on the membrane fraction. In ovariectomized adult mice, we assessed the effects of E4 alone (E4: 0.3-3.0mg/kg twice daily) or in combination with E2 (E2:5µg/kg twice daily) on the negative feedback regulation of the secretion of the luteinizing hormone (LH) and the expression of two E2-regulated proteins: kisspeptin (KP) and progesterone receptor (PR). When used alone, the highest dose of E4 regulated LH secretion to a level similar as E2 and increased the number of PR-expressing neurons in the ventromedial hypothalamic nucleus (VMH) and in the preoptic area (POA), but had not significant effect on the number of KP neurons in the anteroventral periventricular nucleus (AVPV). By contrast, when administered along with E2, E4 had no effect on the negative feedback induced by E2. In conclusion, the results show that E4 exerts a dose-dependent action similar to that of E2 on the secretion of LH and that high doses of E4 increases the expression of PR in the preoptic area and the ventromedial hypothalamic nucleus. Together these suggest that the negative feedback of estrogens on LH secretion depends on nuclear-depend but no membrane-dependent signaling and of estrogens. [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 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 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 ULiege; GERARD, Arlette ULiege; HENNUY, Benoit ULiege 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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