Enrichment analysis and experimental study of BPA-induced male reproductive damage toxicity pathways and key apoptosis signaling pathways

Wenbo YUAN; Wenbin LIU; Hongqiang CHEN; Zili CHAI; Guanghui ZHANG; Jia CAO

doi:10.16016/j.1000-5404.202009210

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Enrichment analysis and experimental study of BPA-induced male reproductive damage toxicity pathways and key apoptosis signaling pathways

更新时间：2026-01-09

- Enrichment analysis and experimental study of BPA-induced male reproductive damage toxicity pathways and key apoptosis signaling pathways
- Journal of Third Military Medical University Vol. 43, Issue 1, Pages: 38-44(2021)
- 作者机构：
- 作者简介：
- 基金信息：
  
  the National Key Research and Development Program of China(2017YFC1002001);the Key Program of National Natural Science Foundation of China(81630087)
- DOI：10.16016/j.1000-5404.202009210
  CLC：
- Received：24 September 2020，
  
  Published：15 January 2021
- 稿件说明：
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Wenbo YUAN, Wenbin LIU, Hongqiang CHEN, et al. Enrichment analysis and experimental study of BPA-induced male reproductive damage toxicity pathways and key apoptosis signaling pathways[J]. Journal of Third Military Medical University, 2021, 43(1): 38-44.
DOI：

Wenbo YUAN, Wenbin LIU, Hongqiang CHEN, et al. Enrichment analysis and experimental study of BPA-induced male reproductive damage toxicity pathways and key apoptosis signaling pathways[J]. Journal of Third Military Medical University, 2021, 43(1): 38-44. DOI： 10.16016/j.1000-5404.202009210.

摘要

Abstract

Objective

To explore the possible key pathways in the male reproductive toxicity induced by exposure to low-dose bisphenol A (BPA).

Methods

BPA-related genes were screened based on Comparative Toxicogenomics Database (CTD). Functional enrichment analysis was used for these genes to explore the possible pathways and identify the key genes in related pathways. Mouse spermatogonia cell line GC-2 cells were treated with BPA at a final concentration of 0 (DMSO control group)

40 and 80 μmol/L for 72 h. Then the changes of cell morphology and apoptotic rate were observed. The mRNA and protein expression levels of the obtained key genes were detected by RT-qPCR and Western blotting

respectively.

Results

A total of 1 460 BPA-related genes were screened out from the CTD database. Gene Ontology (GO) enrichment analysis showed that these genes were significantly enriched in molecular biological processes

such as reproductive system development and reproductive structure development

and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that they were significantly enriched in HIF-1 and PI3K-Akt signaling pathways (

0.01). Visual analysis showed that the key genes in the pathway were HIF-1α

PKC and P300/CBP

and PI3K

JAK

P53 and BCL-2. The apoptotic rate of GC-2 cells exposed to BPA was significantly increased in a dose-dependent manner (

0.05). Compared with the control cells

the mRNA expression levels of PI3K and JAK were significantly down-regulated

while those of P53 and BCL-2 were up-regulated (

0.05). The protein levels of PI3K and BCL-2 were obviously down-regulated

while that of P53 up-regulated (

0.05).

Conclusion

The PI3K-Akt signaling pathway may play an important role in the process of GC-2 cell apoptosis induced by low-dose BPA exposure.

关键词

Keywords

references

MURATA M KANG J H Bisphenol A (BPA) and cell signaling pathways Biotechnol Adv 2018 36 1 311 327 10.1016/j.biotechadv.2017.12.002 MURATA M, KANG J H. Bisphenol A (BPA) and cell signaling pathways[J]. Biotechnol Adv, 2018, 36(1): 311-327. DOI: 10.1016 /j.biotechadv.2017.12.002.

DE TONI L DE ROCCO PONCE M PETRE G C Bisphenols and male reproductive health: from toxicological models to therapeutic hypotheses Front Endocrinol 2020 11 301 10.3389/fendo.2020.00301 DE TONI L, DE ROCCO PONCE M, PETRE G C, et al . Bisphenols and male reproductive health: from toxicological models to therapeutic hypotheses[J ] . Front Endocrinol, 2020, 11: 301. DOI:10.3389/fendo.2020.00301.

RYU D Y RAHMAN M PANG M G Determination of highly sensitive biological cell model systems to screen BPA-related health hazards using pathway studio Int J Mol Sci 2017 18 9 1909 10.3390/ijms18091909 RYU D Y, RAHMAN M, PANG M G. Determination of highly sensitive biological cell model systems to screen BPA-related health hazards using pathway studio[J]. Int J Mol Sci, 2017, 18(9): 1909. DOI:10.3390/ijms18091909.

RAHMAN M S PANG M G Understanding the molecular mechanisms of bisphenol A action in spermatozoa Clin Exp Reprod Med 2019 46 3 99 106 10.5653/cerm.2019.00276 RAHMAN M S, PANG M G. Understanding the molecular mechanisms of bisphenol A action in spermatozoa[J]. Clin Exp Reprod Med, 2019, 46(3): 99-106. DOI:10.5653/cerm.2019.00276.

陈威 . 双酚A暴露引起青春前期大鼠睾丸中精子发生障碍及PI 3 K/Akt/FOXO1信号通路介导的凋亡 [D ] . 武汉 : 华中科技大学 , 2017 . 陈威.双酚A暴露引起青春前期大鼠睾丸中精子发生障碍及PI 3 K/Akt/FOXO1信号通路介导的凋亡[D ] .武汉: 华中科技大学, 2017.

CHEN W . Bisphenol A exposure induces spermatogenesis disorder and apoptosis mediated by PI3K/Akt/FOXO1 signaling pathway in prepubertal rats [D ] . Wuhan : Huazhong University of Science and Technology , 2017 . CHEN W. Bisphenol A exposure induces spermatogenesis disorder and apoptosis mediated by PI3K/Akt/FOXO1 signaling pathway in prepubertal rats[D]. Wuhan: Huazhong University of Science and Technology, 2017.

梁书秋陶亚楠李丹双酚A对小鼠睾丸间质细胞毒性及miR-203-3p和PI3K/AKT/FOXO1信号通路的影响实用药物与临床 2020 23 7 584 588 10.14053/j.cnki.ppcr.202007002 梁书秋, 陶亚楠, 李丹, 等.双酚A对小鼠睾丸间质细胞毒性及miR-203-3p和PI3K/AKT/FOXO1信号通路的影响[J].实用药物与临床, 2020, 23(7): 584-588. DOI: 10.14053/j.cnki.ppcr.202007002.

LIANG S Q TAO Y N LI D Effects of bisphenol A on mouse Leydig cell toxicity and mir-203-3p and PI3K/AKT/FOXO1 signaling pathway Pract Med Clin 2020 23 7 584 588 10.14053/j.cnki.ppcr.202007002 LIANG S Q, TAO Y N, LI D, et al . Effects of bisphenol A on mouse Leydig cell toxicity and mir-203-3p and PI3K/AKT/FOXO1 signaling pathway[J ] . Pract Med Clin, 2020, 23(7): 584-588. DOI: 10.14053/j.cnki.ppcr.202007002.

PERETZ J VROOMAN L RICKE W A Bisphenol A and reproductive health: update of experimental and human evidence, 2007-2013 Environ Heal Perspect 2014 122 8 775 786 10.1289/ehp.1307728 PERETZ J, VROOMAN L, RICKE W A, et al . Bisphenol A and reproductive health: update of experiment al and human evidence, 2007-2013[J ] . Environ Heal Perspect, 2014, 122(8): 775-786. DOI:10.1289/ehp.1307728.

KOIKE E YANAGISAWA R WIN-SHWE T T Exposure to low-dose bisphenol A during the juvenile period of development disrupts the immune system and aggravates allergic airway inflammation in mice Int J Immunopathol Pharmacol 2018 32 2058738418774897 10.1177/2058738418774897 KOIKE E, YANAGISAWA R, WIN-SHWE T T, et al . Exposure to low-dose bisphenol A during the juvenile period of development disrupts the immune system and aggravates allergic airway inflammation in mice[J ] . Int J Immunopathol Pharmacol, 2018, 32: 2058738418774897. DOI:10.1177/2058738418774897.

KOSNIK M B PLANCHART A MARVEL S W Integration of curated and high-throughput screening data to elucidate environmental influences on disease pathways Comput Toxicol 2019 12 100094 10.1016/j.comtox.2019.100094 KOSNIK M B, PLANCHART A, MARVEL S W, et al . Integrat ion of curated and high-throughput screening data to elucidate environmental influences on disease pathways[J ] . Comput Toxicol, 2019, 12: 100094. DOI:10.1016/j.comtox.2019.100094.

DAVIS A P GRONDIN C J JOHNSON R J The comparative toxicogenomics database: update 2017 Nucleic Acids Res 2017 45 d1 D972 D978 10.1093/nar/gkw838 DAVIS A P, GRONDIN C J, JOHNSON R J, et al . The comparative toxicogenomics database: update 2017[J ] . Nucleic Acids Res, 2017, 45(d1): D972-D978. DOI:10.1093/nar/gkw838.

DAVIS A P WIEGERS T C WIEGERS J Chemical-induced phenotypes at CTD help inform the predisease state and construct adverse outcome pathways Toxicol Sci 2018 165 1 145 156 10.1093/toxsci/kfy131 DAVIS A P, WIEGERS T C, WIEGERS J, et al . Chemical-induced phenotypes at CTD help inform the predisease state and construct adverse outcome pathways[J ] . Toxicol Sci, 2018, 165(1): 145-156. DOI:10.1093/toxsci/kfy131.

GRONDIN C J DAVIS A P WIEGERS T C Accessing an expanded exposure science module at the comparative toxicogenomics database Environ Health Perspect 2018 126 1 014501 10.1289/ehp2873 GRONDIN C J, DAVIS A P, WIEGERS T C, et al . Accessing an expanded exposure science module at the comparative toxicogenomics database[J ] . Environ Health Perspect, 2018, 126(1): 014501. DOI:10.1289/ehp2873.

XIE M N BU P L LI F J Neonatal bisphenol A exposure induces meiotic arrest and apoptosis of spermatogenic cells Oncotarget 2016 7 9 10606 10615 10.18632/oncotarget.7218 XIE M N, BU P L, LI F J, et al . Neonatal bisphenol A exposure induces meiotic arrest and apoptosis of spermatogenic cells[J ] . Oncotarget, 2016, 7(9): 10606-10615. DOI:10.18632/oncotarget.7218.

EFIMOVA O A KOLTSOVA A S KRAPIVIN M I Environmental epigenetics and genome flexibility: focus on 5-hydroxymethylcytosine Int J Mol Sci 2020 21 9 3223 10.3390/ijms21093223 EFIMOVA O A, KOLTSOVA A S, KRAPIVIN M I, et al . Environmental epigenetics and genome flexibility: focus on 5-hydroxymethylcytosine[J ] . Int J Mol Sci, 2020, 21(9): 3223. DOI:10.3390/ijms21093223.

ZHAO W LIU J WANG D Effect of silencing HIF-1alpha gene on testicle spermatogenesis function in varicocele rats Cell Tissue Res 2019 378 3 543 554 10.1007/s00441-019-03064-0 ZHAO W, LIU J, WANG D, et al . Effect of silencing HIF-1alpha gene on testicle spermatogenesis function in varicocele rats[J ] . Cell Tissue Res, 2019, 378(3): 543-554. DOI: 10.1007/s00441-019-03064-0.

HU X MA J J VIKASH V Thymoquinone augments cisplatin-induced apoptosis on esophageal carcinoma through mitigating the activation of JAK2/STAT3 pathway Dig Dis Sci 2018 63 1 126 134 10.1007/s10620-017-4856-8 HU X, MA J J, VIKASH V, et al . Thymoquinone augments cisplatin-induced apoptosis on esophageal carcinoma through mitigating the activation of JAK2/STAT3 pathway[J ] . Dig Dis Sci, 2018, 63(1): 126-134. DOI:10.1007/s10620-017-4856-8.

ZHAO X B QIN Y NIU Y L Matrine inhibits hypoxia/reoxygenation-induced apoptosis of cardiac microvascular endothelial cells in rats via the JAK2/STAT3 signaling pathway Biomed Pharmacother 2018 106 117 124 10.1016/j.biopha.2018.06.003 ZHAO X B, QIN Y, NIU Y L, et al . Matrine inhibits hypoxia/reoxygenation-induced apoptosis of cardiac microvascular endothelial cells in rats via the JAK2/STAT3 signaling pathway[J ] . Biomed Pharmacother, 2018, 106: 117-124. DOI:10.1016/j.biopha.2018.06.003.

ZHENG C LIU T LIU H Role of BCL-2 family proteins in apoptosis and its regulation Curr Protein Pept Sci 2020 21 8 799 806 10.2174/1389203721666191227122252 ZHENG C, LIU T, LIU H, et al . Role of BCL-2 family proteins in apoptosis and its regulation[J ] . Curr Protein Pept Sci, 2020, 21(8): 799-806. DOI: 10.2174/1389203721666191227122252.

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