Neonatal bisphenol A exposure induces meiotic arrest and apoptosis of spermatogenic cells

Xie, Meng; Bu, Pengli; Li, Fengjie; Lan, Shijian; Wu, Hongjuan; Lu, Yuan; Wang, Ying

doi:10.18632/oncotarget.7218

Cited by 62 publications

(35 citation statements)

References 40 publications

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“…Subcutaneous injection is an appropriate route for BPA delivery into the neonatal mice to assess its effects on testicular development. The reason why we chose subcutaneous injection as the route of BPA administration was explained in another paper (Xie et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Effects of bisphenol A exposure on DNA integrity and protamination of mouse spermatozoa

et al. 2019

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Background Bisphenol A is widely used in the manufacture of polycarbonate plastics and has caused increasing concern over its potential adverse impacts on spermatogenesis. However, the effect of bisphenol A on spermiogenesis is yet to be explored. Objectives To evaluate whether bisphenol A has adverse effects on DNA integrity and protamination of spermatogenic cell. Materials and methods Newborn male mice were subcutaneously injected with bisphenol A (0.1, 5 mg/kg body weight, n = 15) or coin oil (control group, n = 20) daily from post‐natal day 1 until 35. At post‐natal day 70, epididymis caudal spermatozoa and testes were collected. Sperm count, sperm motility, and sperm morphology were analyzed. The sperm chromatin structure assay was performed to examine the sperm DNA fragmentation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method was used to assess apoptosis of spermatogenic cells. The ultrastructural features of testicular sections were examined under a transmission electron microscope. Western blot and RT‐PCR were used to detect the expression levels of transition protein (Tnp) 1 and Tnp2, protamine (Prm) 1 and Prm2 protein, and mRNA in mice testes. Results Bisphenol A significantly reduced sperm counts, impaired sperm motility, and increased the percentage of malformed spermatozoa. Poor sperm chromatin integrity and increased TUNEL‐positive spermatogenic cells were also observed in mice exposed to bisphenol A. Ultrastructural analysis of testes showed that bisphenol A exposure caused incomplete chromatin condensation, retention of residual cytoplasm, and abnormal acrosome formation. In addition, the relative expression levels of Tnp2 and Prm2 in mice testes decreased significantly in bisphenol A groups. Discussion and conclusion Our findings identified that neonatal bisphenol A exposure may negatively contribute to the sperm quality in adult mice. Mechanistically, we showed that bisphenol A reduced sperm chromatin integrity along with increased DNA damage, which may be due to poor protamination of spermatozoa.

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Section: Discussionmentioning

confidence: 99%

Effects of bisphenol A exposure on DNA integrity and protamination of mouse spermatozoa

et al. 2019

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“…Xu et al [ 48 ] found that BPA could interfere with ERα signaling in the developing hippocampus in an ER-dependent manner. Neonatal BPA exposure disrupted meiosis progression during the first wave of spermatogenesis and increased the expression of ERα and PCNA in the developing testes [ 49 ]. However, few studies have explored the possible mechanisms of how BPA increases ERα expression.…”

Section: Discussionmentioning

confidence: 99%

Low dose of Bisphenol A enhance the susceptibility of thyroid carcinoma stimulated by DHPN and iodine excess in F344 rats

Zhang

et al. 2017

Oncotarget

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Thyroid carcinoma (TC) is the most common endocrine neoplasm. The risk of TC as a second primary malignancy (SPM) of breast cancer is significantly increased. Bisphenol A (BPA) is a widely contacted xenoestrogen and increases susceptibility to breast cancer through binding to estrogen receptor alpha (ERα). However, the effect of BPA on thyroid carcinogenesis has not been fully demonstrated. This present study aimed to characterize the effects of BPA on the development of TC using a Fischer 344 (F344) rat model. In this study, we established a TC model using female F344 rats pretreated with N-Bis (2-hydroxypropyl) nitrosamine (DHPN) at a single dose of 2800 mg/kg (the DA group) or without DHPN (the DN group), followed by stimulation with BPA at the level of 250 μg/kg (BPA250) or 1000 μg/kg (BPA1000) and a basic diet containing potassium iodine (KI, 1000 μg/L) for 64 weeks. We demonstrated that the incidence of TC in the BPA250 + KI of DA groups reached the highest at 50%, the incidence of thyroid hyperplasia lesions (including both tumors and focal hyperplasia lesions) in the BPA1000 + KI of DA groups reached 100% (P < 0.05). ERα protein and immunochemistry expression was upregulated in the BPA-exposed groups and the immunochemistry scores were positively correlated with PCNA. Thus, the present results indicate that BPA could enhance the susceptibility to TC stimulated by DHPN and iodine excess. ERα is probably involved in the proliferation effect of BPA. BPA or KI alone could not increase TC incidence.

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“…PCNA is a cell cycle protein in the nucleus and functions in DNA synthesis ( 32 ). PCNA is commonly used as a marker to assess the state of cell proliferation ( 33 ). The results of the current study demonstrated that ADRP silencing decreased the expression level of PCNA in PDGF-treated VSMCs.…”

Section: Discussionmentioning

confidence: 99%

Adipose differentiation-related protein knockdown inhibits vascular smooth muscle cell proliferation and migration and attenuates neointima formation

Zhao

Han

Hong

et al. 2017

Molecular Medicine Reports

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Vascular smooth muscle cells (VSMCs) have an important role in atherosclerosis development. Evidence has demonstrated that adipose differentiation-related protein (ADRP) is associated with foam cell formation and atherosclerosis progression. However, to the best of our knowledge, no previous studies have investigated the role of ADRP knockdown in platelet-derived growth factor (PDGF)-stimulated proliferation and migration of VSMCs in vitro. Furthermore, the effect of ADRP knockdown on neointima formation in vivo remains unclear. In the present study, primary human aortic VSMCs were incubated with PDGF following ADRP small interfering (si)RNA transfection. Cell viability, migration and cell cycle distribution were analyzed by MTT, wound healing and Transwell assays and flow cytometry, respectively. Extracellular signal-regulated kinase (ERK), phosphorylated (p)-ERK, Akt, p-Akt, proliferating cell nuclear antigen (PCNA), matrix metalloproteinase (MMP)-2 and MMP-9 protein levels were determined by western blotting. Apolipoprotein E−/− mice fed an atherogenic diet were injected with siADRP or control siRNA twice a week. After 3 weeks of therapy, aortas were excised and ADRP mRNA and protein expression was determined. Neointima formation was assessed by hematoxylin and eosin staining. The results of the current study demonstrated that ADRP knockdown significantly inhibited PDGF-induced increases in VSMC viability, caused G1 phase cell cycle arrest and decreased PCNA expression. Knockdown of ADRP inhibited PDGF-induced migration of VSMCs by reducing MMP protein expression and activity. In addition, the present study also demonstrated that ADRP knockdown inhibited ERK and Akt signaling pathways in response to PDGF. Furthermore, siADRP administration suppressed neointima formation in the mouse model. The results of the present study indicate that ADRP may be a potential target for the treatment of atherosclerosis.

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Neonatal bisphenol A exposure induces meiotic arrest and apoptosis of spermatogenic cells

Cited by 62 publications

References 40 publications

Effects of bisphenol A exposure on DNA integrity and protamination of mouse spermatozoa

Effects of bisphenol A exposure on DNA integrity and protamination of mouse spermatozoa

Low dose of Bisphenol A enhance the susceptibility of thyroid carcinoma stimulated by DHPN and iodine excess in F344 rats

Adipose differentiation-related protein knockdown inhibits vascular smooth muscle cell proliferation and migration and attenuates neointima formation

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