A single neonatal administration of Bisphenol A induces higher tumour weight associated to changes in tumour microenvironment in the adulthood.
Margarita Isabel Palacios-ArreolaKaren Elizabeth Nava-CastroVíctor Hugo Del Río-AraizaNashla Yazmín Pérez-SánchezJorge Morales MontorPublished in: Scientific reports (2017)
BPA is an oestrogenic endocrine disrupting chemical compound. Exposure to BPA in as early as pregnancy leads to lifelong effects. Since endocrine and immune systems interact in a bidirectional manner, endocrine disruption may cause permanent alterations of the immune system, affecting a future anti-tumoral response. Neonate (PND 3) female syngeneic BALB/c mice were exposed to a single dose of 250 µg/kg BPA. Once sexual maturity was reached, a mammary tumour was induced injecting 4T1 cells in situ, these cells are derived from a spontaneous adenocarcinoma in a BALB/c mouse and therefore allows for an immunocompetent recipient. After 25 days of injection, showing no major endocrine alterations, BPA-exposed mice developed larger tumours. Tumour leukocytic infiltrate analysis revealed a higher proportion of regulatory T lymphocytes in the BPA-exposed group. RT-PCR analysis of tumour samples showed a decreased expression of TNF-α and IFN-γ, as well as the M2 macrophage marker Fizz-1 in the BPA-exposed group. Flow cytometry analysis revealed differences in ERα expression by T lymphocytes, macrophages and NK cells, both associated to BPA exposure and tumour development. These findings show a new aspect whereby early life BPA exposure can contribute to breast cancer development and progression by modulating the anti-tumoral immune response.
Keyphrases
- early life
- immune response
- flow cytometry
- poor prognosis
- stem cells
- single cell
- mental health
- nk cells
- induced apoptosis
- adipose tissue
- rheumatoid arthritis
- high fat diet induced
- physical activity
- insulin resistance
- dendritic cells
- metabolic syndrome
- transcription factor
- signaling pathway
- oxidative stress
- preterm birth
- radiation therapy
- skeletal muscle
- diabetic rats
- binding protein
- pregnant women
- drug induced
- high glucose
- ultrasound guided
- endoplasmic reticulum
- cell proliferation
- young adults