scholarly journals Neonatal exposure to bisphenol A modifies the abundance of estrogen receptor α transcripts with alternative 5′-untranslated regions in the female rat preoptic area

2007 ◽  
Vol 194 (1) ◽  
pp. 201-212 ◽  
Author(s):  
Lucas Monje ◽  
Jorgelina Varayoud ◽  
Enrique H Luque ◽  
Jorge G Ramos
Keyword(s):  
Estrogen Receptor ◽  
Bisphenol A ◽  
Low Dose ◽  
Preoptic Area ◽  
Methylation Status ◽  
Estrogen Receptor Α ◽  
Female Rats ◽  
Untranslated Regions ◽  
Neonatal Exposure ◽  
High Dose

The xenoestrogen bisphenol A (BPA) is commonly ingested by humans. We examined the effects of neonatal exposure to low versus high doses of BPA over the control of estrogen receptor α (ERα) expression in the preoptic area (POA) of prepubertal female rats. Pups received s.c. injections every 48 h of BPA (high dose, 20 mg/kg and low dose, 0.05 mg/kg) or diethylstilbestrol (DES, 0.02 mg/kg) from postnatal day (PND) 1 to PND7 and were killed at PND8 or PND21. Relative expression of ERα transcripts containing alternative 5′-untranslated regions OS, ON, O, OT, and E1 in POA were evaluated by RT-PCR. Methylation status of ERα promoters was determined by bisulfited DNA restriction analysis and ERα protein by immunohistochemistry. In PND8, the high dose of BPA and DES diminished total ERα mRNA levels, mediated by the decreased expression of ERα-O and ERα-OT variants. In contrast, the low dose of BPA augmented total ERα mRNA by increasing the expression of the ERα-E1 variant. In PND21, both BPA doses increased total ERα mRNA by means of the augmented expression of ERα-O and ERα-OT variants. In PND21, the methylation status of the ERα promoters and the circulating levels of estradiol were similar in all experimental groups. At PND8 and PND21, DES and the high dose of BPA decreased, while the low dose of BPA increased ERα protein in the POA. These findings show that neonatal BPA exposure alters the abundance of hypothalamic ERα transcript variants and protein in a dose-dependent manner.

scholarly journals The estrogen receptor α Σ3 mRNA splicing variant is differentially regulated by estrogen and progesterone in the rat uterus

2005 ◽  
Vol 186 (1) ◽  
pp. 51-60 ◽  
Author(s):  
J Varayoud ◽  
J G Ramos ◽  
L Monje ◽  
V Bosquiazzo ◽  
M Muñoz-de-Toro ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Alternative Splicing ◽  
Estrous Cycle ◽  
Low Dose ◽  
Estrogen Receptor Α ◽  
Mrna Splicing ◽  
Female Rats ◽  
Rt Pcr ◽  
Mrna Isoforms ◽  
Rat Uterus

The gene for estrogen receptor α (ERα) has been shown to be under complex hormonal control and its activity can be regulated by mRNA alternative splicing. Here we examined the regulation of ERα transcription and translation in the rat uterus by ovarian steroid hormones. We examined whether expression of ERα mRNA splice isoforms is hormonally regulated in ovariectomized (OVX) and cycling rats. Adult OVX female rats were treated daily with 17-β estradiol (E2) (0.05 μg/rat or 5 μg/rat), progesterone (P4) (1 mg/rat) or a combination of both hormones for 4 days. Animals were killed 24 h after the last injection and uterine horns were removed. In order to determine whether ERα mRNA isoforms are differentially expressed under various physiological conditions, animals were evaluated at proestrus, estrus and diestrus. The ERα protein and mRNA were detected by immunohistochemistry and comparative RT-PCR analysis respectively. The presence of ERα mRNA isoforms was evaluated using a nested RT-PCR assay. In OVX control rats, ERα mRNA and protein levels were high, demonstrating a constitutive expression of the ERα gene in the uterus. When animals received P4 or the high dose of E2, a significant decrease in both ERα mRNA and protein was observed in the uterus. However, when rats were protein was treated with the low dose of E2, only the ERα down-regulated; no changes were observed in ERα mRNA expression. In addition to the full-length ERα mRNA, OVX control rat uteri expressed three shorter transcripts: Σ3, Σ4 and Σ3,4 (lacking exon 3, exon 4, or both 3 and 4 respectively). Surprisingly, when OVX animals were treated with P4, the low dose of E2 or a combination of both steroids, expression of the Σ3 isoform was completely abolished. During the estrous cycle, all ERα mRNA splicing variants were detected at proestrus and estrus. However, in diestrus, significant low levels of the Σ3 isoform were observed. In summary, our results suggest a dose-dependent relationship between E2 concentrations and the level of control in the ERα transcription–translation cascade. Moreover, the alternative splicing of the ERα primary transcript is influenced by the hormonal milieu, suggesting that these events could affect the estrogen responsiveness of the rat uterus during the estrous cycle.

scholarly journals Neonatal Exposure to Bisphenol A Alters Rat Uterine Implantation-Associated Gene Expression and Reduces the Number of Implantation Sites

Endocrinology ◽  
2011 ◽  
Vol 152 (3) ◽  
pp. 1101-1111 ◽  
Author(s):  
Jorgelina Varayoud ◽  
Jorge G. Ramos ◽  
Verónica L. Bosquiazzo ◽  
Melina Lower ◽  
Mónica Muñoz-de-Toro ◽  
...  
Keyword(s):  
Gene Expression ◽  
Estrogen Receptor ◽  
Bisphenol A ◽  
Steroid Receptors ◽  
Estrogen Receptor Α ◽  
Receptor Expression ◽  
Female Rats ◽  
Postnatal Exposure ◽  
Long Term Effects ◽  
Implantation Sites

Endocrine disrupters have been associated with reproductive pathologies such as infertility and gynecological tumors. Using a rat model of early postnatal exposure to bisphenol A (BPA), we evaluated the long-term effects on 1) female reproductive performance, 2) uterine homeobox A10 (Hoxa10) and Hoxa10-target gene expression, and 3) ovarian steroid levels and uterine estrogen receptor α and progesterone (P) receptor expression. Newborn female rats received vehicle, BPA.05 (0.05 mg/kg · d), BPA20 (20 mg/kg · d), diethylstilbestrol.2 (0.2 μg/kg · d), or diethylstilbestrol 20 (20 μg/kg · d) on postnatal d 1, 3, 5, and 7. A significant decrease in the number of implantation sites was assessed in the xenoestrogen-exposed females. To address the molecular effects of postnatal xenoestrogen exposure on the pregnant uterus, we evaluated the expression of implantation-associated genes on d 5 of pregnancy (preimplantation uterus). All xenoestrogen-treated rats showed a lower expression of Hoxa10. In the same animals, two Hoxa10-downstream genes were misregulated in the uterus. β3Integrin, which is up-regulated by Hoxa10 in controls, was decreased, whereas empty spiracles homolog 2, which is down-regulated by Hoxa10, was increased. Furthermore a clear down-regulation of estrogen receptor α and P receptor expression was detected without changes in estradiol and P serum levels. The early exposure to BPA produced a lower number of implantation sites in association with a defective uterine environment during the preimplantation period. Alterations in the endocrine-regulated Hoxa10 gene pathways (steroid receptors—Hoxa10—β3integrin/empty spiracles homolog 2) could explain, at least in part, the BPA effects on the implantation process.

scholarly journals Persistent vs transient alteration of folliculogenesis and estrous cycle after neonatal vs adult exposure to Bisphenol A

Endocrinology ◽  
2019 ◽  
Author(s):  
David López-Rodríguez ◽  
Delphine Franssen ◽  
Elena Sevrin ◽  
Arlette Gérard ◽  
Cédric Balsat ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Estrous Cycle ◽  
Corn Oil ◽  
Female Rats ◽  
Neonatal Exposure ◽  
High Dose ◽  
Corpora Lutea ◽  
Lh Surge ◽  
Primordial Follicles ◽  
Adult Exposure

Abstract 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 aims at comparing the effects of neonatal versus adult exposure to a very low or a high dose of BPA for two weeks on ovulation and folliculogenesis and exploring 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 novel reproductive peptide Phoenixin indicated a disruption of the hypothalamic control of the preovulatory LH surge by BPA.

scholarly journals Delayed 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

Endocrinology ◽  
2016 ◽  
Vol 157 (5) ◽  
pp. 1740-1750 ◽  
Author(s):  
Delphine Franssen ◽  
Arlette Gérard ◽  
Benoit Hennuy ◽  
Anne-Françoise Donneau ◽  
Jean-Pierre Bourguignon ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Sexual Maturation ◽  
Low Dose ◽  
Ex Vivo ◽  
Female Rats ◽  
High Dose ◽  
Sequencing Analysis ◽  
Female Rat ◽  
Vaginal Opening ◽  
Gabaergic Neurotransmission

Abstract Rat sexual maturation is preceded by a reduction of the interpulse interval (IPI) of 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·d, 25 μg/kg·d, or 5 mg/kg·d from postnatal day (PND)1 to PND5 or PND15. Exposure to 25 ng/kg·d of BPA for 5 or 15 days was followed by a delay in developmental reduction of GnRH IPI studied ex vivo on PND20. 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·d for 15 days resulted in a premature reduction in GnRH IPI and a trend toward early vaginal opening. RNA sequencing analysis on PND20 indicated that exposure to BPA resulted in opposing dose effects on the mRNA expression of hypothalamic genes involved in gamma aminobutyric acid A (GABAA) 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.

Low dose neonatal exposure to bisphenol A affects emotional and social functions in a sex dependent manner in rats

2011 ◽  
Vol 71 ◽  
pp. e280-e281
Author(s):  
Yuki Tsuneyoshi ◽  
Akira Masuda ◽  
Kimiya Narikiyo ◽  
Nami Someya ◽  
Shuji Aou
Keyword(s):  
Bisphenol A ◽  
Low Dose ◽  
Neonatal Exposure ◽  
Dependent Manner ◽  
Social Functions

Low-dose perinatal diethylstilbestrol exposure affected behaviors and hypothalamic estrogen receptor-α-positive cells in the mouse

2004 ◽  
Vol 26 (2) ◽  
pp. 261-269 ◽  
Author(s):  
Mika Tanaka ◽  
Ritsuko Ohtani-Kaneko ◽  
Makoto Yokosuka ◽  
Chiho Watanabe
Keyword(s):  
Estrogen Receptor ◽  
Low Dose ◽  
Estrogen Receptor Α

Synthesis of bio-based epoxy monomers from natural allyl- and vinyl phenols and the estimation of their affinity to the estrogen receptor α by molecular docking

2016 ◽  
Vol 40 (9) ◽  
pp. 7701-7710 ◽  
Author(s):  
Erika Zago ◽  
Eric Dubreucq ◽  
Jérôme Lecomte ◽  
Pierre Villeneuve ◽  
Frédéric Fine ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Molecular Docking ◽  
Phenolic Compounds ◽  
Bisphenol A ◽  
Estrogen Receptor Α ◽  
Diglycidyl Ether ◽  
Metathesis Reaction

Potential substitutes of diglycidyl ether of bisphenol A (DGEBA) were synthesized by the metathesis reaction of glycidylated biobased phenolic compounds.

Male gender increases sensitivity to renal injury in response to cholesterol loading

2003 ◽  
Vol 284 (4) ◽  
pp. F718-F726 ◽  
Author(s):  
Diana M. Attia ◽  
Roel Goldschmeding ◽  
Mahmoud A. Attia ◽  
Peter Boer ◽  
Hein A. Koomans ◽  
...  
Keyword(s):  
Renal Injury ◽  
Low Dose ◽  
Plasma Cholesterol ◽  
A Priori ◽  
No Synthase ◽  
Male Gender ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Cholesterol Feeding

Males are at greater risk for renal injury than females. This may relate to nitric oxide (NO) availability, because female rats have higher renal endothelial NO synthase (NOS) levels. Previously, our laboratory found susceptibility to proteinuria induced by NOS inhibition in male compared with female rats. Dyslipidemia and hypercholesterolemia dose dependently decreased renal NOS activity and caused renal injury in female rats. We hypothesized that exposure of male rats to hypercholesterolemia would lead to more renal injury in male than in female rats due to an a priori lower renal NO system. Female and male rats were fed no, low-dose, or high-dose cholesterol for 24 wk. Cholesterol feeding dose dependently increased proteinuria in both female and male rats, but male rats developed more proteinuria at similar plasma cholesterol ( P < 0.001). Control males had lower renal NOS activity than control females (4.44 ± 0.18 vs. 7.46 ± 0.37 pmol · min−1 · mg protein−1; P < 0.05), and cholesterol feeding decreased renal NOS activity in males and in females ( P < 0.05). Cholesterol-fed males developed significantly more vascular, glomerular, and tubulointerstitial monocyte/macrophage influx and injury than females. Thus under baseline conditions, male rats have lower renal NOS activity than female rats. This may explain why male rats are more sensitive to renal injury by factors that decrease NO availability, such as hypercholesterolemia.

scholarly journals Estrogen Receptor α Gene Promoter 0/B Usage in the Rat Sexually Dimorphic Nucleus of the Preoptic Area

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1923-1928 ◽  
Author(s):  
Tomohiro Hamada ◽  
Yasuo Sakuma
Keyword(s):  
Estrogen Receptor ◽  
Sexual Differentiation ◽  
Preoptic Area ◽  
Gene Promoter ◽  
Estrogen Receptor Α ◽  
Egfp Expression ◽  
Sexually Dimorphic ◽  
Transgenic Rats ◽  
The Core ◽  
Sexually Dimorphic Nucleus

The volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) is two to four times larger in male rats than in females; however, the mechanism for the establishment of sexual dimorphism and the function of this nucleus is almost unknown. Perinatal estrogen can cause sexual dimorphism via the estrogen receptor α (ERα). Recently, transgenic rats were generated that express enhanced green fluorescent protein (EGFP) under the control of the ERα gene promoter 0/B to tag ERα-positive neurons in the brain. In the present study, we examined whether this EGFP expression could be a marker for the SDN-POA in adults. EGFP-labeled cells were distributed in the core of the SDN-POA (0/B-SDN) of male and female transgenic rats, in accordance with the Nissl staining and immunoreactivity for the SDN marker, calbindin. They were also immunoreactive for ERα. The core was bigger in volume and contained more 0/B-SDN neurons in males than in females. The EGFP-tagged cells were packed more densely in the female core than that in males. Subcutaneous injection of 100 μg 17β-estradiol to females on the day of birth, or orchidectomy of male neonates, reversed the sexually dimorphic phenotype of the volume of the 0/B-SDN, despite not affecting the cell number. We suggest that this EGFP expression in the SDN-POA could be a useful marker to clarify the sexual differentiation and function of the SDN-POA. Moreover, the ERα gene promoter 0/B plays a key role in the organization of the sexual differentiation of the SDN-POA.

Sign in / Sign up

Export Citation Format

Share Document