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.

scholarly journals Multigenerational and transgenerational impact of paternal bisphenol A exposure on male fertility in a mouse model

2020 ◽  
Vol 35 (8) ◽  
pp. 1740-1752 ◽  
Author(s):  
Md Saidur Rahman ◽  
Won-Ki Pang ◽  
Do-Yeal Ryu ◽  
Yoo-Jin Park ◽  
Myung-Geol Pang
Keyword(s):  
Dna Methylation ◽  
Bisphenol A ◽  
Large Scale ◽  
Corn Oil ◽  
Sperm Count ◽  
Future Generations ◽  
High Dose ◽  
Male Mice ◽  
Paternal Exposure ◽  
Methylation Patterns

Abstract STUDY QUESTION How does paternal exposure to bisphenol A (BPA) affect the fertility of male offspring in mice in future generations? SUMMARY ANSWER Paternal exposure to BPA adversely affects spermatogenesis, several important sperm functions and DNA methylation patterns in spermatozoa, which have both multigenerational (in F0 and F1) and partial transgenerational (mainly noticed in F2, but F3) impacts on the fertility of the offspring. WHAT IS KNOWN ALREADY BPA, a synthetic endocrine disruptor, is used extensively to manufacture polycarbonate plastics and epoxy resins. Growing evidence suggests that exposure to BPA during the developmental stages results in atypical reproductive phenotypes that could persist for generations to come. STUDY DESIGN, SIZE, DURATION CD-1 male mice (F0) were treated with BPA (5 or 50 mg/kg body weight per day (bw/day)) or ethinylestradiol (EE) (0.4 μg/kg bw/day) for 6 weeks. Control mice were treated with vehicle (corn oil) only. The treated male mice were bred with untreated female mice to produce first filial generation (F1 offspring). The F2 and F3 offspring were produced similarly, without further exposure to BPA. PARTICIPANTS/MATERIALS, SETTING, METHODS Histological changes in the testis along with functional, biochemical and epigenetic (DNA methylation) properties of spermatozoa were investigated. Subsequently, each parameter of the F0–F3 generations was compared between BPA-treated mice and control mice. MAIN RESULTS AND THE ROLE OF CHANCE Paternal BPA exposure disrupted spermatogenesis by decreasing the size and number of testicular seminiferous epithelial cells, which eventually led to a decline in the total sperm count of F0–F2 offspring (P &lt; 0.05). We further showed that a high BPA dose decreased sperm motility in F0–F2 males by mediating the overproduction of reactive oxygen species (F0–F1) and decreasing intracellular ATP (F0–F2) in spermatozoa (P &lt; 0.05). These changes in spermatozoa were associated with altered global DNA methylation patterns in the spermatozoa of F0–F3 males (P &lt; 0.05). Furthermore, we noticed that BPA compromised sperm fertility in mice from the F0–F2 (in the both dose groups) and F3 generations (in the high-dose group only). The overall reproductive toxicity of BPA was equivalent to or higher (high dose) than that of the tested dose of EE. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION Further research is required to determine the variables (e.g. lowest BPA dose) that are capable of producing changes in sperm function and fertility in future generations. WIDER IMPLICATIONS OF THE FINDINGS These results may shed light on how occupational exposure to BPA can affect offspring fertility in humans. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (Grant No. NRF-2018R1A6A1A03025159). M.S.R. was supported by Korea Research Fellowship Program through the NRF funded by the Ministry of Science and ICT (Grant No. 2017H1D3A1A02013844). There are no competing interests.

Investigation of the effects of bisphenol-A exposure on lymphoid system in prenatal stage

2020 ◽  
Vol 36 (7) ◽  
pp. 502-513
Author(s):  
Işil Aydemir ◽  
Caner Özbey ◽  
Oktay Özkan ◽  
Şadiye Kum ◽  
Mehmet İbrahim Tuğlu
Keyword(s):  
Lymph Node ◽  
Bisphenol A ◽  
Tissue Damage ◽  
Corn Oil ◽  
Histopathological Examination ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Organ Function ◽  
Pregnant Rats

Bisphenol-A (BPA) used in the production of plastic materials is a temperature-soluble agent. It also has a steroid hormone-like activity; therefore, it poses a danger to human health. In our study, we aimed to investigate the effects of BPA on lymph node and spleen in male rats exposed to this agent during prenatal stage. The pregnant female rats were divided into four groups: control, sham, low dose (300 µg/kg BPA), and high dose (900 µg/kg BPA). BPA was dissolved in 1 mL of corn oil and administered to the pregnant rats every day during pregnancy. On the 21st and 45th day after the birth, male rats’ lymph node and spleen samples were taken and histopathological examination was performed. Samples were stained with hematoxylin and eosin to determine the general histological appearance, and with CD3 and CD20 immunohistochemically. The results of staining were evaluated by H-score, and statistical analysis was performed. In the samples, BPA applications were not found to cause significant tissue damage. But there was a significant decrease in the immunoreactivities of CD3 and CD20 after BPA applications in both 21st and 45th day samples. After high dose BPA administration, decreased CD3 immunoreactivity was statistically significant. It is thought that BPA does not cause histologically significant tissue damage, but it may impair organ function at cellular level. The investigation of molecules involved in organ function will be useful in revealing the mechanisms that will cause dysfunction.

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.

The Synthetic Hest Shock Protein (Hsp) 90 Inhibitor EC141 Induces Degradation of the Bcr-Abl p190 Protein and Apoptosis of Philadelphia Chromosome (Ph)-Positive Acute Lymphoblastic Leukemia (ALL) Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2784-2784
Author(s):  
Alessandra Ferrajoli ◽  
Yongtao Wang ◽  
Susan M. O’Brien ◽  
Stefan H. Faderl ◽  
David M. Harris ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Bone Marrow Cells ◽  
Apoptotic Cell ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Protein Kinase Inhibitors ◽  
High Dose ◽  
Dependent Manner ◽  
Protein Levels ◽  
Dose Dependent

Abstract High dose chemotherapy of Ph+ ALL is rarely curative and clinical responses to protein kinase inhibitors have been transient. Although new regimens combining chemotherapy with Bcr-Abl kinase inhibitors improve survival, the long-term prognosis of patients with Ph+ ALL remains guarded. Thus, novel therapeutic strategies are needed. Hsp90 is a ubiquitous molecular chaperone protein required for the folding, activation and assembly of mediators of signal transduction, cell cycle control, and transcription regulation. The Hsp90 inhibitor EC141 (Biogen Idec, Inc.) blocks the chaperone activity of Hsp90 and induces proteasomal degradation of it’s client proteins. Because Hsp90 is a chaperone of Bcr-Abl we investigated the activity of EC141 against the Ph+ ALL B-cell lines Z-119, Z-181 and Z-33 (Estrov et al. J Cell Physiol166: 618, 1996; Leukemia10:1534, 1996). First we studied the effect of EC141 on Hsp levels in Ph+ ALL cells. EC141 (50 nM) down-regulated the protein levels of Hsp90 and upregulated those of Hsp70. Then, the effect of EC141 on the proliferation of Ph+ ALL cells was evaluated using the MTT assay. EC141 inhibited the growth and metabolic activity of Z-119, Z-181 and Z-33 Ph+ ALL cells in a dose-dependent manner at concentrations ranging from 1 to 100 nM. Similar results were obtained with primary bone marrow cells from patients with Ph+ ALL. Using the ALL blast colony culture assay we found that EC141 inhibited the proliferation of marrow-derived ALL colony-forming cells in a dose-dependent fashion. To explore the mechanism of action Z-181 were incubated cells with increasing concentrations of EC141; immunoprecipitation and Western immunoblotting were used to detect changes in cellular protein levels. EC141 degraded the Bcr-Abl p190 protein and inhibited the phosphorylation of CrkL in a dose-dependent manner. Furthermore, exposure of Z-181 cells to EC141 resulted in a time- and dose-dependent activation of procaspase 3, cleavage of poly (adenosine diphosphate-ribose) polymerase and apoptotic cell death as assessed by Annexin V. Taken together, our data suggest that EC141 degrades the Bcr-Abl p190 protein, inhibits proliferation, and induces apoptosis of Ph+ ALL cells. Additional studies aimed at investigating the in vivo activity of EC141 in Ph+ ALL are warranted.

scholarly journals Effects of Bisphenol A and 4-Tert-octylphenol on Embryo Implantation Failure in Mouse

2018 ◽  
Author(s):  
Dinh Nam Tran ◽  
Eui-Man Jung ◽  
Changhwan Ahn ◽  
Jae-Hwan Lee ◽  
Yeong-Min Yoo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bisphenol A ◽  
Calcium Transport ◽  
Embryo Implantation ◽  
Implantation Site ◽  
Mrna Levels ◽  
Implantation Failure ◽  
Gene Expressions ◽  
Expression Levels ◽  
Implantation Sites

Miscarriage due to blastocyst implantation failure occurs in up to two-thirds of all miscarriage cases in human. The calcium ion has been shown to be involved in many cellular signal transduction pathways as well as in the regulation of cell adhesion, which is necessary for the embryo implantation process. Exposure to endocrine-disrupting chemicals (EDs) during early gestation results in disruption of intrauterine implantation and uterine reception, leading to implantation failure. In this study, ovarian estrogen (E2), bisphenol A (BPA), or 4-tert-octylphenol (OP), with or without ICI 182,780 (ICI) were injected subcutaneously from gestation day 1 to gestation day 3 post-coitus. The expression levels of the calcium transport genes were assessed in maternal uteri and implantation sites. The number of implantation sites was significantly low in the OP group, and implantation sites were absent in the E2 and EDs+ICI groups. There were different calcium transient transport channel expression levels in uterus and implantation site samples. The levels of TRPV5 and TRPV6 gene expression were significantly increased by EDs with/without ICI treatment in uterus. Whereas, TRPV5 and TRPV6 gene expression were significantly lower in implantation sites samples. NCX1 and PMCA1 mRNA levels were significantly decreased by OP and BPA in the implantation site samples. Compared to vehicle treatment in uterus, both the MUC1 mRNA and protein levels were markedly high in all but the BPA group. Taken together, these results suggest that both BPA and OP can impair embryo implantation through alteration of calcium transport gene expressions and by affecting uterine receptivity.

scholarly journals Rottlerin Suppresses Fat Accumulation by Inhibiting Adipogenesis and De Novo Lipogenesis in 3T3-L1 Adipocytes

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1224-1224
Author(s):  
Ye Jin Kim ◽  
Gwang-woong !Go
Keyword(s):  
Lipid Accumulation ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Dependent Manner ◽  
Gene Expressions ◽  
Alcoholic Fatty Liver ◽  
Protein Levels ◽  
Funding Sources ◽  
Mrna Gene ◽  
Oil Red O

Abstract Objectives Rottlerin is isolated from Mallotus japonicus, a rich-in polyphenol. Rottlerin is a PKC delta inhibitor known for an uncoupler of oxidative phosphorylation and anti-neoplastic agent. However, the effect of anti-obesity is not conclusive. This study hypothesized that rottlerin inhibits lipid accumulation in adipocytes. Methods 3T3-L1 cells were maintained with DMEM containing 10% BCS and 1% penicillin. The cells were seeded in a 6-well plate with a density of 8 × 104 followed by cultured for 4 days until reaching 120% confluency and incubated in a differentiation medium for 6 days. Rottlerin was incubated with differentiation media (0, 1, 2, and 4 µM). Cells were harvested after treatment for measurement of Oil Red O stating, immunoblotting, and RT-PCR. Results Differentiated 3T3-L1 adipocytes were stained using the Oil Red O, which stains triglycerides into the red. Lipid accumulation was significantly inhibited in 4 µM of rottlerin (P &lt; 0.001). In protein levels, PPARγ, an adipogenesis marker, was reduced dose-dependently decreased (P &lt; 0.001), indicating lipid droplet formation reduced. FAS and SCD1 were diminished by rottlerin treated groups (all P &lt; 0.001). ACC-pS79/ACC was increased by rottlerin (P = 0.02). In mRNA gene expressions, C/EBPα was reduced by rottlerin in a dose-dependent manner (P &lt; 0.001), and PPARγ tend to be decreased by rottlerin (P = 0.06). FAS and SREBP1 were inhibited by rottlerin (P &lt; 0.01). SCD1 was dramatically reduced by rottlerin (P &lt; 0.001). Conclusions We found that rottlerin reduces lipid accumulation by inhibiting adipogenesis in differentiated 3T3-L1 adipocytes. This suggests that rottlerin is a potential nutraceutical for treating dyslipidemia, non-alcoholic fatty liver disease, and obesity. Funding Sources This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science and ICT; MSIT).

scholarly journals Influence of nonylphenol exposure on basic growth, development, and thyroid tissue structure in F1 male rats

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7039
Author(s):  
Lin Wang ◽  
Jie Xu ◽  
Feng Zeng ◽  
Xiangjun Fu ◽  
Weihong Xu ◽  
...  
Keyword(s):  
Dose Group ◽  
Corn Oil ◽  
Thyroid Tissue ◽  
Male Rats ◽  
Follicular Epithelium ◽  
High Dose Group ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Lactational Exposure

Objective Environmental endocrine disruptors (EEDs) with a weak ability to mimic estrogen have been associated with thyroid dysfunction. However, little is known about the effect of nonylphenol (NP), a well-known EED, on thyroid structure. The present study evaluates whether gestational and lactational exposure to NP impacts growth and thyroid structure in F1 male rats. Methods A total of 60 rats were gavaged with NP (25, 50, and 100 mg/kg), estradiol (E2, 30 μg/kg/day), and corn oil alone (vehicle control) from gestational day 6 to postnatal day (PND) 21. Serum thyroid hormones free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone levels were detected by automated chemiluminescence immunoassay analyzer. The NP level in the thyroid was measured using high-performance liquid chromatography. The ultrastructure of follicular epithelial cells was examined using transmission electron microscopy. Histopathology was conducted using hematoxylin and eosin staining. Results On PND 0, exposure to 50 and 100 mg/kg/day NP led to a significant decrease in the average litter size, litter weight and number of live pups per litter compared to the control group (P < 0.05). Dams exposed to NP during perinatal period demonstrated decreased serum levels of FT3 and FT4 in F1 male rats, when compared to the control group (P < 0.05). The NP level in the control group was 3.39 ± 0.08 ng/mg, while NP levels in the low, middle, and high dose groups ranged from 5.20 to 11.00 ng/mg. Exposure caused a dose-related increase in NP level in the thyroid of male pups (P < 0.01). The thicknesses of the thyroid follicular epithelium were 2.06 ± 0.37 μm in the control group and 3.97 ± 1.61 μm in the high-dose group. The thickness of the thyroid follicular epithelium increased with an increase in treatment dose in a dose-dependent manner (P < 0.05). The sizes of the thyroid follicles were 1,405.53 ± 866.62 μm2 in the control group and 317.49 ± 231.15 μm2 in the high-dose group. With increasing NP dosages, animals showed a decreased size of the thyroid follicle (P < 0.01). Thyroid follicular cells of NP-treated rats showed mildly swollen mitochondria and dilated rough endoplasmic reticulum in the cytoplasm. Conclusion Nonylphenol can cross the placental barrier and accumulate in the thyroid of F1 male rats. Gestational and lactational exposure to NP in dams impacted both development and growth of pups and damaged the ultrastructure of their thyroid tissue, which may further negatively influence normal thyroid function.

scholarly journals The Effect of Exposure to Bisphenol A on Spermatozoon and the Expression of Tight Junction Protein Occludin in Male Mice

Dose-Response ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 155932582092674
Author(s):  
Tingshuai Cao ◽  
Yuanchao Cao ◽  
Hongqiang Wang ◽  
Peitao Wang ◽  
Xinsheng Wang ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Tight Junction ◽  
Sperm Motility ◽  
Corn Oil ◽  
Sperm Count ◽  
High Dose ◽  
Male Mice ◽  
Irreversible Damage ◽  
Junction Protein ◽  
Higher Doses

Although bisphenol A (BPA) has been associated with impaired spermatogenesis, the mechanisms remain unclear. Tight junction occludin plays important roles in spermatogenesis. The objective of the present study was to explore the effects of BPA exposure in adolescent mice. Male mice were orally treated with low-dose (0.05 mg/kg/d), middle-dose (5.0 mg/kg/d), or high-dose (50 mg/kg/d) BPA in corn oil from postnatal day (PND) 35 to 65. Animals were killed on PND 65 and PND 125. On PND 65, the sperm count, sperm motility, and the expression of occludin showed a dose-related decline. On PND 125, the sperm count, sperm motility, and the expression of occludin were in recovery. However, there remained significant decreases in these parameters in the 50 mg/kg/d group on PND 125 compared with the control. The dose-related effects on the measured parameters and occludin expression suggest an early suppressive or damaging effect on the blood–testis barrier followed by recovery after dosing ceased. At a BPA dose of 50 mg/kg/d, recovery did not occur, suggesting that higher doses of BPA may cause irreversible damage to reproduction in male mice.

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 Effects of Bisphenol A and 4-tert-Octylphenol on Embryo Implantation Failure in Mouse

2018 ◽  
Vol 15 (8) ◽  
pp. 1614 ◽  
Author(s):  
Dinh Nam Tran ◽  
Eui-Man Jung ◽  
Changhwan Ahn ◽  
Jae-Hwan Lee ◽  
Yeong-Min Yoo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bisphenol A ◽  
Calcium Transport ◽  
Embryo Implantation ◽  
Implantation Site ◽  
Mrna Levels ◽  
Implantation Failure ◽  
Gene Expressions ◽  
Expression Levels ◽  
Implantation Sites

Miscarriage due to blastocyst implantation failure occurs in up to two-thirds of all human miscarriage cases. Calcium ion has been shown to be involved in many cellular signal transduction pathways as well as in the regulation of cell adhesion, which is necessary for the embryo implantation process. Exposure to endocrine-disrupting chemicals (EDs) during early gestation results in disruption of intrauterine implantation and uterine reception, leading to implantation failure. In this study, ovarian estrogen (E2), bisphenol A (BPA), or 4-tert-octylphenol (OP), with or without ICI 182,780 (ICI) were injected subcutaneously from gestation day 1 to gestation day 3 post-coitus. The expression levels of the calcium transport genes were assessed in maternal uteri and implantation sites. The number of implantation sites was significantly low in the OP group, and implantation sites were absent in the E2, ICI and EDs + ICI groups. There were different calcium transient transport channel expression levels in uterus and implantation site samples. The levels of TRPV5 and TRPV6 gene expression were significantly increased by EDs with/without ICI treatment in utero. Meanwhile, TRPV5 and TRPV6 gene expression were significantly lower in implantation sites samples. NCX1 and PMCA1 mRNA levels were significantly decreased by OP and BPA in the implantation site samples. Compared to vehicle treatment in the uterus, both the MUC1 mRNA and protein levels were markedly high in all but the BPA group. Taken together, these results suggest that both BPA and OP can impair embryo implantation through alteration of calcium transport gene expressions and by affecting uterine receptivity.

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