Butylated hydroxyanisole (BHA), a synthetic phenolic antioxidant (SPA), has been used as a food additive. However, BHA acts as an environmental hormone, i.e., endocrine disruptor. Here, we investigated BHA-induced male reproductive dysfunction in mouse Leydig and Sertoli cells. We found that BHA suppressed proliferation and induced cell cycle arrest in TM3 and TM4 cells. Furthermore, we investigated mitochondrial permeabilization, expression profiles of pro-apoptotic and anti-apoptotic proteins, calcium influx, and endoplasmic reticulum (ER) stress in testicular cells after BHA treatment. The results indicated that BHA-mediated calcium dysregulation and ER stress downregulated steroidogenesis- and spermatogenesis-related genes in mouse testis cell lines. Additionally, proliferation of both TM3 and TM4 cells in response to BHA treatment was regulated via the Mapk and Akt signaling pathways. Therefore, constant BHA exposure may lead to testicular toxicity via mitochondrial dysfunction, ER stress, and abnormal calcium levels in the testis.
Bibliographical noteFunding Information:
This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute funded by the Ministry of Health & Welfare (grant number: HI17C0929 ), and the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (MSIT) (No. 2018R1C1B6009048 ).
© 2019 Elsevier B.V.
- ER stress
- Leydig cell
- Mitochondrial apoptosis
- Sertoli cell
ASJC Scopus subject areas
- Environmental Engineering
- Environmental Chemistry
- Waste Management and Disposal