title: Mammalian target of rapamycin/eukaryotic initiation factor 4F pathway regulates follicle growth and development of theca cells in mice.
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 100ngmL-1Rheb and 500ngmL-1GTP for 48h) 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 (10nM rapamycin for 24h) 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.
authors.affiliation: Animal Science and Technology College, Beijing University of Agriculture, Beijing 102206, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Galactophore Breast Clinic, Peking University School of Oncology, Beijing 100142, China.
authors.forename: Xiao-Ran
authors.initials: XR
authors.lastname: Liu
authors.affiliation: Animal Science and Technology College, Beijing University of Agriculture, Beijing 102206, China.
authors.forename: Yong-Chun
authors.initials: YC
authors.lastname: Cao
authors.affiliation: Animal Science and Technology College, Beijing University of Agriculture, Beijing 102206, China.
authors.forename: Jin-Ling
authors.initials: JL
authors.lastname: Tian
authors.affiliation: Animal Science and Technology College, Beijing University of Agriculture, Beijing 102206, China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhen
authors.affiliation: Animal Science and Technology College, Beijing University of Agriculture, Beijing 102206, China.
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Luo
authors.affiliation: Animal Science and Technology College, Beijing University of Agriculture, Beijing 102206, China.
authors.forename: Xin-Mei
authors.initials: XM
authors.lastname: Wang
authors.affiliation: College of Animal Science and Technology, China Agricultural University, Beijing 100083, China.
authors.forename: Jian-Hui
authors.initials: JH
authors.lastname: Tian
authors.affiliation: Animal Science and Technology College, Beijing University of Agriculture, Beijing 102206, China.
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Gao
mesh_terms: D000818:Animals; D039562:Eukaryotic Initiation Factor-4F / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006160:Guanosine Triphosphate / Q000494:pharmacology; D051379:Mice; D006080:Ovarian Follicle / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D000076205:Ras Homolog Enriched in Brain Protein / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D013799:Theca Cells / Q000187:drug effects / Q000378:metabolism*
chemical_list: D039562:Eukaryotic Initiation Factor-4F; D000076205:Ras Homolog Enriched in Brain Protein; D006160:Guanosine Triphosphate; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus