Frontiers in Cell and Developmental Biology (Jul 2020)
Hormone-Like Effects of 4-Vinylcyclohexene Diepoxide on Follicular Development
- Lian Bao Cao,
- Lian Bao Cao,
- Lian Bao Cao,
- Hong Bin Liu,
- Hong Bin Liu,
- Hong Bin Liu,
- Gang Lu,
- Gang Lu,
- Yue Lv,
- Yue Lv,
- Yue Lv,
- Chi Kwan Leung,
- Chi Kwan Leung,
- Chi Kwan Leung,
- Chi Kwan Leung,
- Yan Zhi Du,
- Yan Zhi Du,
- Wu Ming Wang,
- Wu Ming Wang,
- Zhi Qiang Xiong,
- Zhi Qiang Xiong,
- Zhi Qiang Xiong,
- Xian Wei Su,
- Xian Wei Su,
- Xian Wei Su,
- Xian Wei Su,
- Hong Jian Li,
- Hong Jian Li,
- Hong Jian Li,
- Hong Jian Li,
- Zi-Jiang Chen,
- Zi-Jiang Chen,
- Zi-Jiang Chen,
- Zi-Jiang Chen,
- Jin Long Ma,
- Jin Long Ma,
- Jin Long Ma,
- Jin Long Ma,
- Wai Yee Chan,
- Wai Yee Chan
Affiliations
- Lian Bao Cao
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Lian Bao Cao
- CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China
- Lian Bao Cao
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China
- Hong Bin Liu
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Hong Bin Liu
- CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China
- Hong Bin Liu
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China
- Gang Lu
- CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China
- Gang Lu
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China
- Yue Lv
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Yue Lv
- CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China
- Yue Lv
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China
- Chi Kwan Leung
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Chi Kwan Leung
- CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China
- Chi Kwan Leung
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China
- Chi Kwan Leung
- SDIVF R&D Centre, Hong Kong Science and Technology Parks, Sha Tin, China
- Yan Zhi Du
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China
- Yan Zhi Du
- Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Wu Ming Wang
- CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China
- Wu Ming Wang
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China
- Zhi Qiang Xiong
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Zhi Qiang Xiong
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China
- Zhi Qiang Xiong
- SDIVF R&D Centre, Hong Kong Science and Technology Parks, Sha Tin, China
- Xian Wei Su
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Xian Wei Su
- CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China
- Xian Wei Su
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China
- Xian Wei Su
- SDIVF R&D Centre, Hong Kong Science and Technology Parks, Sha Tin, China
- Hong Jian Li
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Hong Jian Li
- CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China
- Hong Jian Li
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China
- Hong Jian Li
- SDIVF R&D Centre, Hong Kong Science and Technology Parks, Sha Tin, China
- Zi-Jiang Chen
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Zi-Jiang Chen
- CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China
- Zi-Jiang Chen
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China
- Zi-Jiang Chen
- Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Jin Long Ma
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Jin Long Ma
- CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China
- Jin Long Ma
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China
- Jin Long Ma
- SDIVF R&D Centre, Hong Kong Science and Technology Parks, Sha Tin, China
- Wai Yee Chan
- CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China
- Wai Yee Chan
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China
- DOI
- https://doi.org/10.3389/fcell.2020.00587
- Journal volume & issue
-
Vol. 8
Abstract
Background4-vinylcyclohexene diepoxide (VCD) has long been considered a hazardous occupational chemical that promotes ovarian failure. However, VCD is also used as a research compound to chemically induce animal models of premature ovarian insufficiency (POI), and in related work we unexpectedly found that VCD apparently exhibits both dose- and duration-dependent opposing, hormone-like effects on the maintenance of the primordial follicle pool, follicle development, and ovulation induction.ResultsWe conducted experiments with cultured murine ovaries and performed transplantation experiments using postnatal day (PD) 2 and PD12 mice and found that low-dose, short-term exposure to VCD (VCDlow) actually protects the primordial/primary follicle pool and improves the functional ovarian reserve (FOR) by disrupting follicular atresia. VCDlow inhibits follicular apoptosis and regulates the Pten-PI3K-Foxo3a pathway. Short-term VCD exposure in vivo (80 mg/kg, 5 days) significantly increases the number of superovulated metaphase II oocytes, preovulatory follicles, and corpus luteum in middle-aged mice with diminished ovarian reserve (DOR). We demonstrate that low-dose but not high-dose VCD promotes aromatase levels in granulosa cells (GCs), thereby enhancing the levels of estradiol secretion.ConclusionOur study illustrates a previously unappreciated, hormone-like action for the occupational “ovotoxin” molecule VCD and strongly suggests that VCDlow should be explored for its potential utility for treating human ovarian follicular development disorders, including subfertility in perimenopausal women.
Keywords
