Dibutyl phthalate promotes juvenile Sertoli cell proliferation by decreasing the levels of the E3 ubiquitin ligase Pellino 2.
Environ Health
; 19(1): 87, 2020 08 01.
Article
in En
| MEDLINE
| ID: mdl-32738922
ABSTRACT
BACKGROUND:
A previous study showed that dibutyl phthalate (DBP) exposure disrupted the growth of testicular Sertoli cells (SCs). In the present study, we aimed to investigate the potential mechanism by which DBP promotes juvenile SC proliferation in vivo and in vitro.METHODS:
Timed pregnant BALB/c mice were exposed to vehicle, or DBP (50, 250, and 500 mg/kg/day) from 12.5 days of gestation until delivery. In vitro, CCK-8 and EdU incorporation assays were performed to determine the effect of monobutyl phthalate (MBP), the active metabolite of DBP, on the proliferation of TM4 cells, which are a juvenile testicular SC cell line. Western blotting analysis, quantitative PCR (q-PCR), and flow cytometry were performed to analyse the expression of genes and proteins related to the proliferation and apoptosis of TM4 cells. Coimmunoprecipitation was used to determine the relationship between the ubiquitination of interleukin 1 receptor-associated kinase 1 (IRAK1) and the effect of MBP on promoting the proliferation of TM4 cells.RESULTS:
In the 50 mg/kg/day DBP-exposed male mice offspring, the number of SCs was significantly increased. Consistent with the in vivo results, in vitro experiments revealed that 0.1 mM MBP treatment promoted the proliferation of TM4 cells. Furthermore, the data showed that 0.1 mM MBP-mediated downregulation of the E3 ubiquitin ligase Pellino 2 (Peli2) increased ubiquitination of IRAK1 by K63, which activated MAPK/JNK signalling, leading to the proliferation of TM4 cells.CONCLUSIONS:
Prenatal exposure to DBP led to abnormal proliferation of SCs in prepubertal mice by affecting ubiquitination of the key proliferation-related protein IRAK1 via downregulation of Peli2.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phthalic Acids
/
Plasticizers
/
Sertoli Cells
/
Nuclear Proteins
/
Cell Proliferation
/
Dibutyl Phthalate
Limits:
Animals
Language:
En
Journal:
Environ Health
Journal subject:
SAUDE AMBIENTAL
Year:
2020
Document type:
Article
Affiliation country: