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

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G-protein Coupled Estrogen Receptor Expression in Growth Hormone Secreting and Non-Functioning Adenomas

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/a-1274-1330 ◽

2020 ◽

Author(s):

Hande Mefkure Ozkaya ◽

Muge Sayitoglu ◽

Nil Comunoglu ◽

Eda Sun ◽

Fatma Ela Keskin ◽

...

Keyword(s):

Gene Expression ◽

Estrogen Receptor ◽

Protein Expression ◽

G Protein ◽

Estrogen Receptor Α ◽

Receptor Expression ◽

Positive Correlation ◽

Polymerase Chain ◽

G Protein Coupled ◽

Transforming Gene

Abstract Purpose To evaluate the expression of G-protein coupled estrogen receptor (GPER1), aromatase, estrogen receptor α (ERα), estrogen receptor β (ERβ), pituitary tumor transforming gene (PTTG), and fibroblast growth factor 2 (FGF2) in GH-secreting and non-functioning adenomas (NFA). Methods Thirty patients with acromegaly and 27 patients with NFA were included. Gene expression was determined via quantitative reverse transcription polymerase chain reaction (QRT-PCR). Protein expression was determined via immunohistochemistry. Results There was no difference, in terms of gene expression of aromatase, ERα, PTTG, and FGF2 between the two groups (p>0.05 for all). ERβ gene expression was higher and GPER1 gene expression was lower in GH-secreting adenomas than NFAs (p<0.05 for all). Aromatase and ERβ protein expression was higher in GH-secreting adenomas than NFAs (p=0.01). None of the tumors expressed ERα. GPER1 expression was detected in 62.2% of the GH-secreting adenomas and 45% of NFAs. There was no difference in terms of GPER1, PTTG, FGF2 H scores between the two groups (p>0.05 for all). GPER1 gene expression was positively correlated to ERα, ERβ, PTTG, and FGF2 gene expression (p<0.05 for all). There was a positive correlation between aromatase and GPER1 protein expression (r=0.31; p=0.04). Conclusions GPER1 is expressed at both gene and protein level in a substantial portion of GH-secreting adenomas and NFAs. The finding of a positive correlation between GPER1 and ERα, ERβ, PTTG, and FGF2 gene expression and aromatase and GPER1 protein expression suggests GPER1 along with aromatase and classical ERs might mediate the effects of estrogen through upregulation of PTTG and FGF2.

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Estradiol Stimulates Apolipoprotein A-IV Gene Expression in the Nucleus of the Solitary Tract Through Estrogen Receptor-α

Endocrinology ◽

10.1210/en.2014-1239 ◽

2014 ◽

Vol 155 (10) ◽

pp. 3882-3890 ◽

Cited By ~ 7

Author(s):

Ling Shen ◽

Yin Liu ◽

David Q.H. Wang ◽

Patrick Tso ◽

Stephen C. Woods ◽

...

Keyword(s):

Gene Expression ◽

Estrogen Receptor ◽

Nucleus Tractus Solitarius ◽

Body Weight Gain ◽

Gene Promoter ◽

Estrogen Receptor Α ◽

Inhibitory Effect ◽

Female Rats ◽

Upstream Region ◽

Apolipoprotein A

Abstract Although estrogens have been implicated in the regulation of apolipoprotein A-IV (apo A-IV) gene expression in the nucleus tractus solitarius, previous studies have not defined the molecular mechanism. The aim of this study was to examine the transcriptional mechanisms involved in regulation of apo A-IV gene expression. Using cultured primary neuronal cells from rat embryonic brainstems, we found that treatment with 10nM 17β-estradiol-3-benzoate (E2) or 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (an estrogen receptor [ER]α agonist), but not 2,3-bis(4-hydroxyphenyl)-propionitrile (an ERβ agonist), significantly increased apo A-IV gene expression, compared with vehicle treatment. This effect of E2 was abolished when the cells were incubated with E2 linked to BSA, which prevents E2 from entering cells, implying that a nongenomic mechanism of E2 is not involved. Two putative estrogen response elements were identified at the 5′-upstream region of the apo A-IV gene promoter, but only 1 of them was able to recruit ERα, leading to increased apo A-IV gene expression, as determined by chromatin immunoprecipitation assay and luciferase activity analysis. A cyclic regimen of E2 or 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol treatment for 8 cycles (4 d/cycle, mimicking the ovarian cycle of female rats) in ovariectomized female rats significantly reduced food intake and body weight gain and increased apo A-IV gene expression in the nucleus tractus solitarius, relative to vehicle. These data collectively demonstrate that nuclear ERα is the primary mediator of E2's action on apo A-IV gene expression and suggest that increased signaling of endogenous apo A-IV may at least partially mediate E2-induced inhibitory effect on feeding.

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Gene expression profiling reveals novel regulation by bisphenol-A in estrogen receptor-α-positive human cells

Environmental Research ◽

10.1016/j.envres.2005.05.004 ◽

2006 ◽

Vol 100 (1) ◽

pp. 86-92 ◽

Cited By ~ 45

Author(s):

David W. Singleton ◽

Yuxin Feng ◽

Jun Yang ◽

Alvaro Puga ◽

Adrian V. Lee ◽

...

Keyword(s):

Gene Expression ◽

Estrogen Receptor ◽

Bisphenol A ◽

Gene Expression Profiling ◽

Expression Profiling ◽

Estrogen Receptor Α ◽

Human Cells

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Inhibition of Oxytocin Receptor and Estrogen Receptor-α Expression, But Not Relaxin Receptors (LGR7), in the Myometrium of Late Pregnant Relaxin Gene Knockout Mice

Endocrinology ◽

10.1210/en.2003-0548 ◽

2003 ◽

Vol 144 (10) ◽

pp. 4272-4275 ◽

Cited By ~ 24

Author(s):

Andrew L. Siebel ◽

Helen M. Gehring ◽

Irna Grace T. Reytomas ◽

Laura J. Parry

Keyword(s):

Gene Expression ◽

Estrogen Receptor ◽

Knockout Mice ◽

Gene Knockout ◽

Estrogen Receptor Α ◽

Oxytocin Receptor ◽

Receptor Expression ◽

Late Gestation ◽

Mrna Levels ◽

Gene Knockout Mice

This study used relaxin (RLX) gene knockout mice (Rlx−/−) to investigate the effects of RLX on myometrial oxytocin receptor (OTR) and estrogen receptor (ER)-α gene expression in late gestation. We also characterized the temporal expression of the RLX receptor (LGR7) and demonstrated gene transcripts in the myometrium of Rlx+/+ and Rlx−/− mice. There was a significant (P < 0.05) decrease in myometrial LGR7 gene expression on d 17.5 and 18.5 post coitum (pc) compared with earlier stages of gestation, but no differences between Rlx+/+ and Rlx−/− mice. Myometrial OTR mRNA levels increased at the end of gestation in Rlx+/+ but not Rlx−/− mice. ERα gene expression was up-regulated on d 14.5 pc in Rlx+/+ mice, with mRNA levels remaining high throughout late gestation. In contrast, ERα mRNA levels were significantly lower in Rlx−/− mice on d 14.5 and 18.5 pc. These data show that the increases in myometrial OTR and ERα expression in late pregnant Rlx+/+ mice were attenuated in Rlx−/− mice. The effects of RLX on OTRs are probably mediated via activation of ERα. Finally, RLX receptor expression in the myometrium of Rlx−/− mice did not differ from wild-type mice, implying that RLX does not influence expression of its receptor.

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Bisphenol A (BPA) induces progesterone receptor expression in an estrogen receptor α-dependent manner in perinatal brain

Neurotoxicology and Teratology ◽

10.1016/j.ntt.2020.106864 ◽

2020 ◽

Vol 78 ◽

pp. 106864

Author(s):

Allyssa Fahrenkopf ◽

Christine K. Wagner

Keyword(s):

Estrogen Receptor ◽

Progesterone Receptor ◽

Bisphenol A ◽

Estrogen Receptor Α ◽

Receptor Expression ◽

Dependent Manner ◽

Progesterone Receptor Expression

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

Journal of Endocrinology ◽

10.1677/joe-07-0014 ◽

2007 ◽

Vol 194 (1) ◽

pp. 201-212 ◽

Cited By ~ 69

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.

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Loading-related regulation of gene expression in bone in the contexts of estrogen deficiency, lack of estrogen receptor α and disuse

Bone ◽

10.1016/j.bone.2009.10.021 ◽

2010 ◽

Vol 46 (3) ◽

pp. 628-642 ◽

Cited By ~ 65

Author(s):

Gul Zaman ◽

Leanne K. Saxon ◽

Andrew Sunters ◽

Helen Hilton ◽

Peter Underhill ◽

...

Keyword(s):

Gene Expression ◽

Estrogen Receptor ◽

Regulation Of Gene Expression ◽

Estrogen Receptor Α ◽

Estrogen Deficiency

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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

New Journal of Chemistry ◽

10.1039/c6nj00782a ◽

2016 ◽

Vol 40 (9) ◽

pp. 7701-7710 ◽

Cited By ~ 15

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.

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