scholarly journals Bisphenol A Exposure during Pregnancy Alters the Mortality and Levels of Reproductive Hormones and Genes in Offspring Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Shuang Ma ◽  
Wanyu Shi ◽  
Xiaodan Wang ◽  
Pengyan Song ◽  
Xiuhui Zhong
Keyword(s):  
Bisphenol A ◽  
Reproductive Toxicity ◽  
Female Offspring ◽  
Reproductive Hormones ◽  
Maternal Exposure ◽  
Adult Offspring ◽  
Mrna Levels ◽  
Protein Levels ◽  
Pregnant Mice ◽  
Exposure During Pregnancy

The present study investigated the reproductive toxicity of bisphenol A (BPA) exposure to the mother on the offspring mice. BPA was given to pregnant mice at 50 mg/kg, 500 mg/kg, and 2500 mg/kg BW BPA daily by gavage during the whole gestation period. The offspring mice were sacrificed at 8 weeks of age. Results showed that exposure of BPA to the mother increased the mortality (P<0.05). Maternal exposure of BPA reduced the levels of T (♂) and FSH (♀) (P<0.01) and elevated E2 (♀) level in the adult offspring (P<0.01). BPA exposure caused testicular damage as shown by less Leydig cells and ovarian injury as shown by more vacuoles and less corpus granules in the adult offspring mice. Immunohistochemistry revealed that maternal exposure of BPA increased Bax and decreased Bcl-2 at the protein levels in testicular and ovary tissues in the offspring mice. BPA significantly reduced the expression of StAR in male offspring (P<0.05). Interestingly, the mRNA levels of Cyp11a were significantly decreased in 50 mg/kg groups and were increased in 500 mg/kg group in the males. Reduced Kitlg and elevated Amh at the mRNA levels were detected in the female offspring.

scholarly journals The Role of the FOXO1/β2-AR/p-NF-κB p65 Pathway in the Development of Endometrial Stromal Cells in Pregnant Mice under Restraint Stress

2021 ◽  
Vol 22 (3) ◽  
pp. 1478
Author(s):  
Jiayin Lu ◽  
Yaoxing Chen ◽  
Zixu Wang ◽  
Jing Cao ◽  
Yulan Dong
Keyword(s):  
Oxidative Stress ◽  
Stromal Cells ◽  
Restraint Stress ◽  
Target Genes ◽  
Mrna Levels ◽  
Endometrial Stromal Cells ◽  
Protein Levels ◽  
Pregnant Mice

Restraint stress causes various maternal diseases during pregnancy. β2-Adrenergic receptor (β2-AR) and Forkhead transcription factor class O 1 (FOXO1) are critical factors not only in stress, but also in reproduction. However, the role of FOXO1 in restraint stress, causing changes in the β2-AR pathway in pregnant mice, has been unclear. The aim of this research was to investigate the β2-AR pathway of restraint stress and its impact on the oxidative stress of the maternal uterus. In the study, maternal mice were treated with restraint stress by being restrained in a transparent and ventilated device before sacrifice on Pregnancy Day 5 (P5), Pregnancy Day 10 (P10), Pregnancy Day 15 (P15), and Pregnancy Day 20 (P20) as well as on Non-Pregnancy Day 5 (NP5). Restraint stress augmented blood corticosterone (CORT), norepinephrine (NE), and blood glucose levels, while oestradiol (E2) levels decreased. Moreover, restraint stress increased the mRNA levels of the FOXO family, β2-AR, and even the protein levels of FOXO1 and β2-AR in the uterus and ovaries. Furthermore, restraint stress increased uterine oxidative stress level. In vitro, the protein levels of FOXO1 were also obviously increased when β2-AR was activated in endometrial stromal cells (ESCs). In addition, phosphorylated-nuclear factor kappa-B p65 (p-NF-κB p65) and its target genes decreased significantly when FOXO1 was inhibited. Overall, it can be said that the β2-AR/FOXO1/p-NF-κB p65 pathway was activated when pregnant mice were under restraint stress. This study provides a scientific basis for the origin of psychological stress in pregnant women.

Expression of the breast cancer resistance protein (Bcrp1/Abcg2) in tissues from pregnant mice: effects of pregnancy and correlations with nuclear receptors

2006 ◽  
Vol 291 (6) ◽  
pp. E1295-E1304 ◽  
Author(s):  
Honggang Wang ◽  
Xiaohui Wu ◽  
Kelly Hudkins ◽  
Andrei Mikheev ◽  
Huixia Zhang ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Small Intestine ◽  
Nuclear Receptors ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Cancer Resistance ◽  
Protein Levels ◽  
Pregnant Mice ◽  
Resistance Protein ◽  
Kidney Liver

The breastcancer resistance protein (BCRP) plays an important role in drug disposition, including limiting drug penetration across the placental barrier. Our goal was to investigate the effects of pregnancy on Bcrp1 expression in pregnant mice. We examined Bcrp1 expression in placenta, kidney, liver, and small intestine at various gestational ages. Bcrp1 protein levels peaked at gestation day ( gd) 15 in placenta, at gd 10 and 15 in kidney, and at gd 15 in liver; however, Bcrp1 protein levels in small intestine did not change significantly with gestational ages. Immunohistochemistry analysis revealed that the cellular localization of Bcrp1 in placenta, kidney, liver, and small intestine was not influenced by pregnancy. Bcrp1 mRNA levels were analyzed by quantitative real-time RT-PCR. In general, the effects of pregnancy on Bcrp1 protein somewhat lagged behind the effects on Bcrp1 mRNA. To further investigate the possible roles of nuclear receptors in the regulation of the Bcrp1 gene during pregnancy, we examined mRNA levels of aryl hydrocarbon receptor (AhR), hypoxia-inducible factor 1α (HIF1α), estrogen receptor α (ERα), estrogen receptor β (ERβ), or progesterone receptor and compared them with those of Bcrp1. Bcrp1 mRNA was significantly correlated with mRNA of AhR, HIF1α, and ERβ in placenta, with mRNA of HIF1α in kidney, and with mRNA of AhR and ERα in liver. These data suggest that Bcrp1 expression in mouse tissues can be altered by pregnancy in a gestational age-dependent manner. Such effects are likely mediated by certain nuclear receptors through a transcriptional mechanism.

124 THE REGULATION OF CALCIUM TRANSPORT GENE EXPRESSIONS DURING PREGNANCY AFTER EXPOSURE TO OCTYLPHENOL AND BISPHENOL A

2013 ◽  
Vol 25 (1) ◽  
pp. 209
Author(s):  
S. Kim ◽  
E. B. Jeung
Keyword(s):  
Bisphenol A ◽  
Calcium Transport ◽  
Corn Oil ◽  
Urinary Calcium ◽  
High Dose ◽  
Dependent Manner ◽  
Gene Expressions ◽  
Protein Levels ◽  
Pregnant Mice ◽  
Serum And Urine

Octylphenol (OP) is a degradation product of alkylphenol ethoxylates that are widely used to in rubber, pesticides, and paints. Bisphenol A (BPA) is an organic compound with two functional phenol groups and used to make polycarbonate plastic and epoxy resins, along with other applications. OP and BPA are known as endocrine disruptors that can induce inappropriate estrogenic action, and may disturb natural calcium metabolism. In the present study, the effects of OP and BPA on the calcium levels of serum and urine, and calcium transport genes were investigated in the duodenum and kidney of the pregnant mice. From 6.5 to 16.5 days post-coitus (dpc), 5 pregnant mice for each group were orally given with ethylestradiol (EE, 0.2 mg kg–1 day –1), OP (15, 45, or 135 mg kg–1 day–1) or BPA (5 or 50 mg kg–1 day –1) dissolved in corn oil. The duodenum, kidney, blood, and urine were obtained from the mice at day 18.5 of pregnancy. As a result, serum and urinary calcium levels were decreased by OP and BPA in a dose-dependent manner. The mRNA expression levels of calcium transport genes TRPV6 and CaBP-9k were decreased in the kidney after treatment with OP and BPA, while duodenal expression of TRPV6 was reduced by a high dose of BPA. The protein levels of these genes showed similar pattern with those of mRNA in the kidney and duodenum. The data were analyzed using a one-way ANOVA. P < 0.05 was considered statistically significant. Taken together, OP and BPA altered gene expressions associated with calcium transport in the pregnant mice, which may cause reduced serum and urine calcium levels. These results suggest that estrogenic actions of OP and BPA may lead to influence the calcium levels during pregnancy in the mice.

GRIM-19, a gene associated with retinoid-interferon-induced mortality, affects endometrial receptivity and embryo implantation

2017 ◽  
Vol 29 (7) ◽  
pp. 1447 ◽  
Author(s):  
Yang Yang ◽  
Yanyan Sun ◽  
Laiyang Cheng ◽  
Anna Li ◽  
Yanjun Shen ◽  
...  
Keyword(s):  
Immune Tolerance ◽  
Embryo Implantation ◽  
Pregnant Mouse ◽  
Endometrial Receptivity ◽  
Mrna Levels ◽  
Protein Levels ◽  
Tnf Α ◽  
Pregnant Mice ◽  
Adhesion Rate

GRIM-19 is associated with apoptosis, abnormal proliferation, immune tolerance and malignant transformation, and it also plays an important role in early embryonic development. Although the homologous deletion of GRIM-19 causes embryonic lethality in mice, the precise role of GRIM-19 in embryo implantation has not been elucidated. Here we show that GRIM-19 plays an important role in endometrial receptivity and embryo implantation. Day 1 to Day 6 pregnant mouse uteri were collected. Immunohistochemistry studies revealed the presence of GRIM-19 on the luminal epithelium and glandular epithelium throughout the implantation period in pregnant mice. The protein and mRNA levels of GRIM-19 were markedly decreased on Day 4 of pregnancy in pregnant mice, but there was no change in GRIM-19 levels in a group of pseudopregnant mice. Overexpression of GRIM-19 decreased the adhesion rate of RL95–2–BeWo co-cultured spheroids and increased apoptosis. Furthermore, STAT3 and IL-11 mRNA and protein levels were reduced by overexpressing GRIM-19, but protein and mRNA levels of TNF-α were increased. These findings indicate the involvement of GRIM-19 in the embryo implantation process by regulating adhesion, apoptosis and immune tolerance.

scholarly journals Maternal exposure to a mixture of Bisphenol A and Diethyl Hexyl Phthalate predisposes female offspring to growth retardation and metabolic dysfunction in adulthood

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Josephine Bou Dagher ◽  
Maryam Al Mansi ◽  
Amrita Kaimal ◽  
Katarzyna Rzepka ◽  
Kryzystof Czaja ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Growth Retardation ◽  
Female Offspring ◽  
Maternal Exposure ◽  
Metabolic Dysfunction

scholarly journals Elucidating the role of pigment epithelium-derived factor (PEDF) in metabolic PCOS models

2020 ◽  
Vol 244 (2) ◽  
pp. 297-308 ◽  
Author(s):  
Michal Silber ◽  
Irit Miller ◽  
Hadas Bar-Joseph ◽  
Ido Ben-Ami ◽  
Ruth Shalgi
Keyword(s):  
Pigment Epithelium ◽  
Elevated Serum ◽  
Female Offspring ◽  
Mrna Levels ◽  
Prolonged Incubation ◽  
Protein Levels ◽  
Potential Therapeutic Role ◽  
Endothelial Growth Factor

PCOS is the most common endocrinopathy in women; associated with obesity and insulin resistance (IR). IR leads to accumulation of advanced-glycation-end-products (AGEs) and their receptor, RAGE. PCOS patients have increased levels of vascular endothelial growth factor (VEGF), interleukin 6/8 (IL-6/8) and anti-Mϋllerian-hormone (AMH). PEDF is a secreted-glycoprotein known for its anti-angiogenic and anti-inflammatory properties. We aimed to elucidate the role of PEDF in the pathogenesis and treatment of PCOS. We used a prenatal PCOS mouse model and fed the female offspring a high-fat diet, inducing metabolic PCOS (met.PCOS) characteristics. Female offspring were divided into three groups: control; met.PCOS; met.PCOS + recombinant PEDF (rPEDF). Met.PCOS mice gained more weight, had elevated serum IL-6 and higher mRNA levels of AMH, PEDF and RAGE in their granulosa cells (GCs) than met.PCOS + rPEDF mice. An in vitro Met.PCOS model in human GCs (KGN) line was induced by prolonged incubation with insulin/AGEs, causing development of IR. Under the same conditions, we observed an elevation of VEGF, IL-6/8 mRNAs, concomitantly with an increase in PEDF mRNA, intracellular protein levels, and an elevation of PEDF receptors (PEDF-Rs) mRNA and protein. Simultaneously, a reduction in the secretion of PEDF from GCs, was measured in the medium. The addition of rPEDF (5 nM) activated P38 signaling, implying that PEDF-Rs maintained functionality, and negated AGE-induced elevation of IL-6/8 and VEGF mRNAs. Decreased PEDF secretion may be a major contributor to hyperangiogenesis and chronic inflammation, which lie at the core of PCOS pathogenesis. rPEDF treatment may restore physiological angiogenesis inflammatory balance, thus suggesting a potential therapeutic role in PCOS.

scholarly journals Perinatal exposure to low-dose bisphenol A affects the neuroendocrine stress response in rats

2013 ◽  
Vol 220 (3) ◽  
pp. 207-218 ◽  
Author(s):  
Emily Panagiotidou ◽  
Sophia Zerva ◽  
Dimitra J Mitsiou ◽  
Michael N Alexis ◽  
Efthymia Kitraki
Keyword(s):  
Stress Response ◽  
Bisphenol A ◽  
Hpa Axis ◽  
Chronic Exposure ◽  
Glucocorticoid Receptors ◽  
Low Dose ◽  
Female Offspring ◽  
Zona Fasciculata ◽  
Mrna Levels ◽  
Brain Physiology

Bisphenol A (BPA) is an estrogen-mimicking endocrine disruptor. Early-life exposures to low doses of BPA exert long-lasting effects on animals' reproductive and brain physiology. However, little is known about the effects of BPA on the stress–response system. Given the interaction of sex and stress hormones, we examined the effect of a low perinatal BPA exposure on the function of the hypothalamic–pituitary–adrenal (HPA) axis at rest and upon application of acute stress. Throughout pregnancy and lactation rats received daily 40 μg BPA/kg body weight orally via cornflakes. We studied the effect of this low but chronic exposure to BPA in the male and female offspring at puberty. BPA exposure led to abnormal adrenal histology including reduced zona reticularis especially in male offspring, hyperplasia of zona fasciculata in both sexes, and increased adrenal weight in female offspring. BPA-treated females had increased basal corticosterone and reduced hypothalamic glucocorticoid receptors (GR) levels. Stressed BPA-exposed females exhibited anxiety-like behavioral coping, a less rigorous corticosterone response, and did not downregulate GR in the hypothalamus, compared with control females. BPA-exposed males exhibited a heightened corticosterone stress response compared with females; they also displayed increased pro-opiomelanocortin mRNA levels and retained the prestress levels of pituitary corticotropin-releasing hormone-receptor 1, compared with control males. We found that perinatal chronic exposure to a low dose of BPA perturbs the basal and stress-induced activity of the HPA axis in a sexually dimorphic manner at adolescence. Exposure to BPA might contribute to increased susceptibility to stress-related disorders in later life.

scholarly journals Maternal-Fetal Glucocorticoid Milieu Programs Hypothalamic-Pituitary-Thyroid Function of Adult Offspring

Endocrinology ◽  
2004 ◽  
Vol 145 (9) ◽  
pp. 4068-4072 ◽  
Author(s):  
Jennifer Slone-Wilcoxon ◽  
Eva E. Redei
Keyword(s):  
Thyroid Function ◽  
Female Offspring ◽  
Adult Offspring ◽  
Mrna Levels ◽  
Continuous Release ◽  
Fetal Plasma ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
Low Levels

Abstract To assess the role of maternal glucocorticoid milieu on the hypothalamic-pituitary-thyroid function of the offspring, we adrenalectomized (ADX) pregnant dams on gestation d 8 and implanted a placebo pellet or a continuous release 50- or 75-mg corticosterone (CORT) pellet. Maternal ADX led to realignment of the balance between maternal and fetal plasma CORT levels, resulting in an increase in CORT of fetal origin in the maternal compartment. Maternal ADX and low levels of CORT replacement had no discernable effect on maternal pituitary-thyroid measures. In contrast, the increase in fetal CORT, as a consequence of the absence of maternal glucocorticoids, decreased birth weight in neonates, decreased adult hypothalamic TRH mRNA levels, and increased plasma TSH levels in both male and female adult offspring, all of which were reversed by administration of basal levels of CORT to the pregnant ADX dam. Decreased plasma T3 concentrations in female offspring were reversed by administration of the higher levels of CORT to the ADX dams. Our data indicate that maternal glucocorticoids modulate the developing hypothalamic-pituitary-thyroid axis.

Developmental exposure to bisphenol A leads to cardiometabolic dysfunction in adult mouse offspring

2012 ◽  
Vol 3 (4) ◽  
pp. 287-292 ◽  
Author(s):  
F. R. Cagampang ◽  
C. Torrens ◽  
F. W. Anthony ◽  
M. A. Hanson
Keyword(s):  
Bisphenol A ◽  
Receptor Gene ◽  
Perinatal Period ◽  
Female Offspring ◽  
Metabolic Dysfunction ◽  
Developmental Exposure ◽  
Adverse Health Outcomes ◽  
Pregnant Mice ◽  
Receptor Gene Expression ◽  
Increased Susceptibility

Bisphenol A (BPA) is a chemical compound that has adverse health outcomes in adults when exposed during the perinatal period. However, its effect on cardiovascular function remains to be elucidated. In this study, we examined the effects of daily administration of BPA to pregnant mice from gestational days 11 to 19 on cardiometabolic outcomes in the adult offspring. Prenatal BPA exposure resulted in altered growth trajectory and organ size, increase adiposity and impaired glucose homeostasis in male and female offspring. In addition, these BPA offspring exhibited raised systolic blood pressure, and in the males this was accompanied by impaired vascular tone. The aortas in females, but not in males, from the BPA group also showed reduced estrogen receptor gene expression. These results indicate that prenatal exposure to BPA increased susceptibility of the offspring to developing cardiovascular and metabolic dysfunction later in life.

The Effects of Vitamin K1 and Warfarin on Prothrombin Expression in Human Hepatoblastoma (HepG2) Cells

1992 ◽  
Vol 68 (01) ◽  
pp. 040-047 ◽  
Author(s):  
C Scott Jamison ◽  
Bryan F Burkey ◽  
Sandra J Friezner Degen
Keyword(s):  
Total Protein ◽  
Hepg2 Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Response Analysis ◽  
Secreted Protein ◽  
Mrna Levels ◽  
Vitamin K1 ◽  
Maximal Increase ◽  
Protein Levels ◽  
Warfarin Treatment

SummaryCultures of human hepatoblastoma (HepG2) cells were treated with vitamin K1 or warfarin and prothrombin antigen and mRNA levels were determined. With 3 and 6 h of 10 µg vitamin K1 treatment secreted prothrombin antigen levels, relative to total secreted protein levels, were increased 1.5-fold and 2.1-fold, respectively, over ethanol-treated control levels as determined by an enzyme-linked immunosorbent assay. Dose-response analysis with 3 h of 25 µg/ml vitamin K1 treatment demonstrated a maximal increase of 2.0-fold in secreted prothrombin antigen levels, relative to total secreted protein levels, over ethanol-treated control levels. Pulse-chase analysis with 35S-methionine and immunoprecipitation of 35S-labelled prothrombin demonstrated that, with vitamin K1 treatment (25 µg/ml, 3 h), the rate of prothrombin secretion increased approximately 2-fold and the total amount (intra- and extracellular) of prothrombin synthesized increased approximately 50% over ethanol-treated control levels. Warfarin treatment (1, 5, or 10 µg/ml, 24 h) resulted in decreases in secreted prothrombin antigen levels, relative to total protein levels to approximately 85%, 87% or 81% of ethanol-treated control levels. Analysis of total RNA isolated from these cultures by Northern and solution hybridization techniques demonstrated that prothrombin mRNA was approximately 2.1 kb and that neither vitamin K1 nor warfarin treatment affected the quantity of prothrombin mRNA (ranging from 240–350 prothrombin mRNA molecules per cell). These results demonstrate that vitamin K1 and warfarin, in addition to effects on γ-carboxylation, affect prothrombin synthesis post-transcriptionally, perhaps influencing translation, post-translational processing and/or secretion mechanisms.

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