Identification of a New Theca/Interstitial Cell-Specific Gene and Its Biological Role in Growth of Mouse Ovarian Follicles at the Gonadotropin-Independent Stage
Theca/interstitial cells are responsible for the growth and maturation of ovarian follicles. However, little is known about the theca/interstitial cell-specific genes and their functions. In this study, we explored transcriptomes of theca/interstitial cells by RNA-seq, and the novel biological roles...
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Frontiers Media S.A.
2019-08-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2019.00553/full |
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| author | Masato Aoyama Masato Aoyama Akira Shiraishi Shin Matsubara Kaoru Horie Tomohiro Osugi Tsuyoshi Kawada Keiko Yasuda Honoo Satake |
| author_facet | Masato Aoyama Masato Aoyama Akira Shiraishi Shin Matsubara Kaoru Horie Tomohiro Osugi Tsuyoshi Kawada Keiko Yasuda Honoo Satake |
| author_sort | Masato Aoyama |
| collection | DOAJ |
| description | Theca/interstitial cells are responsible for the growth and maturation of ovarian follicles. However, little is known about the theca/interstitial cell-specific genes and their functions. In this study, we explored transcriptomes of theca/interstitial cells by RNA-seq, and the novel biological roles of a theca cell marker, asporin (Aspn)/periodontal ligament-associated protein 1 (PLAP-1). RNA-seq detected 432 and 62 genes expressed specifically in theca/interstitial cells and granulosa cells isolated from 3-weeks old mouse ovaries. Gene ontology analysis demonstrated that these genes were largely categorized into four major groups: extracellular matrix organization-related terms, chemotaxis-related terms, the angiogenesis-related terms, and morphogenesis-related terms. In situ hybridization demonstrated that the newly detected representative gene, Aspn/PLAP-1, was detected specifically in the outer layer of theca cells in contrast with the expression of the basal lamina-specific gene, Nidgen-1. Intriguingly, an Aspn/PLAP-1 antibody completely arrested the growth of secondary follicles that is the gonadotropin-independent follicle developmental stage. Furthermore, transforming growth factor-β (TGF-β)-triggered signaling was induced by the Aspn/PLAP-1 antibody treatment, which is consistent with the inhibitory effect of Aspn/PLAP-1 on TGF-β. Altogether, these results suggest that theca cells are classified into subpopulations on the basis of new marker genes and their biological functions, and provide evidence that Aspn/PLAP-1 is expressed exclusively in the outer layer of theca cells and plays a pivotal role in the growth of secondary follicles via downregulation of the canonical TGF-β signaling cascade. |
| first_indexed | 2024-12-19T13:07:07Z |
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| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-19T13:07:07Z |
| publishDate | 2019-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-1b79020a13af4e2788a02392279b0a3e2022-12-21T20:20:01ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922019-08-011010.3389/fendo.2019.00553481218Identification of a New Theca/Interstitial Cell-Specific Gene and Its Biological Role in Growth of Mouse Ovarian Follicles at the Gonadotropin-Independent StageMasato Aoyama0Masato Aoyama1Akira Shiraishi2Shin Matsubara3Kaoru Horie4Tomohiro Osugi5Tsuyoshi Kawada6Keiko Yasuda7Honoo Satake8Department of Chemistry, Biology, and Environmental Science, Faculty of Science, Nara Women's University, Nara, JapanBioorganic Research Institute, Suntory Foundation for Life Sciences, Kyoto, JapanBioorganic Research Institute, Suntory Foundation for Life Sciences, Kyoto, JapanBioorganic Research Institute, Suntory Foundation for Life Sciences, Kyoto, JapanDepartment of Chemistry, Biology, and Environmental Science, Faculty of Science, Nara Women's University, Nara, JapanBioorganic Research Institute, Suntory Foundation for Life Sciences, Kyoto, JapanBioorganic Research Institute, Suntory Foundation for Life Sciences, Kyoto, JapanDepartment of Chemistry, Biology, and Environmental Science, Faculty of Science, Nara Women's University, Nara, JapanBioorganic Research Institute, Suntory Foundation for Life Sciences, Kyoto, JapanTheca/interstitial cells are responsible for the growth and maturation of ovarian follicles. However, little is known about the theca/interstitial cell-specific genes and their functions. In this study, we explored transcriptomes of theca/interstitial cells by RNA-seq, and the novel biological roles of a theca cell marker, asporin (Aspn)/periodontal ligament-associated protein 1 (PLAP-1). RNA-seq detected 432 and 62 genes expressed specifically in theca/interstitial cells and granulosa cells isolated from 3-weeks old mouse ovaries. Gene ontology analysis demonstrated that these genes were largely categorized into four major groups: extracellular matrix organization-related terms, chemotaxis-related terms, the angiogenesis-related terms, and morphogenesis-related terms. In situ hybridization demonstrated that the newly detected representative gene, Aspn/PLAP-1, was detected specifically in the outer layer of theca cells in contrast with the expression of the basal lamina-specific gene, Nidgen-1. Intriguingly, an Aspn/PLAP-1 antibody completely arrested the growth of secondary follicles that is the gonadotropin-independent follicle developmental stage. Furthermore, transforming growth factor-β (TGF-β)-triggered signaling was induced by the Aspn/PLAP-1 antibody treatment, which is consistent with the inhibitory effect of Aspn/PLAP-1 on TGF-β. Altogether, these results suggest that theca cells are classified into subpopulations on the basis of new marker genes and their biological functions, and provide evidence that Aspn/PLAP-1 is expressed exclusively in the outer layer of theca cells and plays a pivotal role in the growth of secondary follicles via downregulation of the canonical TGF-β signaling cascade.https://www.frontiersin.org/article/10.3389/fendo.2019.00553/fulltheca cellsecondary folliclefollicle growthtranscriptomeAsporin/PLAP-1 |
| spellingShingle | Masato Aoyama Masato Aoyama Akira Shiraishi Shin Matsubara Kaoru Horie Tomohiro Osugi Tsuyoshi Kawada Keiko Yasuda Honoo Satake Identification of a New Theca/Interstitial Cell-Specific Gene and Its Biological Role in Growth of Mouse Ovarian Follicles at the Gonadotropin-Independent Stage Frontiers in Endocrinology theca cell secondary follicle follicle growth transcriptome Asporin/PLAP-1 |
| title | Identification of a New Theca/Interstitial Cell-Specific Gene and Its Biological Role in Growth of Mouse Ovarian Follicles at the Gonadotropin-Independent Stage |
| title_full | Identification of a New Theca/Interstitial Cell-Specific Gene and Its Biological Role in Growth of Mouse Ovarian Follicles at the Gonadotropin-Independent Stage |
| title_fullStr | Identification of a New Theca/Interstitial Cell-Specific Gene and Its Biological Role in Growth of Mouse Ovarian Follicles at the Gonadotropin-Independent Stage |
| title_full_unstemmed | Identification of a New Theca/Interstitial Cell-Specific Gene and Its Biological Role in Growth of Mouse Ovarian Follicles at the Gonadotropin-Independent Stage |
| title_short | Identification of a New Theca/Interstitial Cell-Specific Gene and Its Biological Role in Growth of Mouse Ovarian Follicles at the Gonadotropin-Independent Stage |
| title_sort | identification of a new theca interstitial cell specific gene and its biological role in growth of mouse ovarian follicles at the gonadotropin independent stage |
| topic | theca cell secondary follicle follicle growth transcriptome Asporin/PLAP-1 |
| url | https://www.frontiersin.org/article/10.3389/fendo.2019.00553/full |
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