Mammalian target of rapamycin/eukaryotic initiation factor 4F pathway regulates follicle growth and development of theca cells in mice
Chao Zhang A , Xiao-Ran Liu B , Yong-Chun Cao A , Jin-Ling Tian A , Di Zhen A , Xiao-Fei Luo A , Xin-Mei Wang A , Jian-Hui Tian C D and Jian-Ming Gao A D
+ Author Affiliations
- Author Affiliations
A Animal Science and Technology College, Beijing University of Agriculture, Beijing 102206, China.
B Galactophore Breast Clinic, Peking University School of Oncology, Beijing 100142, China.
C College of Animal Science and Technology, China Agricultural University, Beijing 100083, China.
D Corresponding author. Email: jianming.gao@hotmail.com
*These authors contributed equally to this work.
Reproduction, Fertility and Development 29(4) 768-777 https://doi.org/10.1071/RD15230
Submitted: 9 June 2015 Accepted: 26 November 2015 Published: 11 January 2016
Abstract
The aim of the present study was to clarify the roles of the mammalian target of rapamycin (mTOR) signalling pathway in follicular growth and development of thecal cells. Using in vivo-grown and in vitro-cultured ovaries, histological changes were evaluated using haematoxylin and eosin (HE) staining. Differentially expressed genes (DEGs) from 0 day post partum (d.p.p.) to 8 d.p.p. ovaries were screened by microarray and verified by quantitative real-time polymerase chain reaction. Forty-two DEGs related to cell proliferation and differentiation were screened out, with most DEGs being related to the to mTOR signalling pathway. Then, 3 d.p.p. ovaries were retrieved and used to verify the role of mTOR signalling in follicle and thecal cell development using its activators (Ras homologue enriched in brain (Rheb) and GTP) and inhibitor (rapamycin). The development of follicles and thecal cells was significantly impaired in ovaries cultured in vitro Day 3 to Day 8. In in vitro-cultured ovaries, Rheb and GTP (is 100 ng mL–1 Rheb and 500 ng mL–1 GTP for 48 h) significantly increased follicle diameter, the percentage of primary and secondary follicles and the umber of thecal cells, and upregulated expression of mTOR, phosphorylated eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1), eukaryotic initiation factor (eIF) 4F and cytochrome P450, family 17, subfamily A, polypeptide 1 (CYP17A1). Rapamycin (10 nM rapamycin for 24 h) had opposite effects to those of Rheb and GTP, and partly abrogated (significant) the effects of Rheb and GTP when added to the culture in combination with these drugs. Thus, mTOR signalling plays an important role in follicle growth and thecal cell development.
Additional keywords: 4EBP1, CYP17A1, follicular growth, GTP, mTOR pathway, ovary, Rheb, thecal cells.
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