A low-testosterone state associated with endometrioma leads to the apoptosis of granulosa cells.
Although endometriosis is suspected to be a cause of premature ovarian insufficiency (POI), the mechanism(s) underlying this process have not been elucidated. Recently, androgens were shown to promote oocyte maturation and to play a role in folliculogenesis. In addition, several reports have documen...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4275210?pdf=render |
| _version_ | 1818581755467137024 |
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| author | Yoshihiro J Ono Akiko Tanabe Yoko Nakamura Hikaru Yamamoto Atsushi Hayashi Tomohito Tanaka Hiroshi Sasaki Masami Hayashi Yoshito Terai Masahide Ohmichi |
| author_facet | Yoshihiro J Ono Akiko Tanabe Yoko Nakamura Hikaru Yamamoto Atsushi Hayashi Tomohito Tanaka Hiroshi Sasaki Masami Hayashi Yoshito Terai Masahide Ohmichi |
| author_sort | Yoshihiro J Ono |
| collection | DOAJ |
| description | Although endometriosis is suspected to be a cause of premature ovarian insufficiency (POI), the mechanism(s) underlying this process have not been elucidated. Recently, androgens were shown to promote oocyte maturation and to play a role in folliculogenesis. In addition, several reports have documented low testosterone levels in the follicular fluid obtained from endometriosis patients. We therefore examined whether the low levels of serum testosterone are associated with the apoptosis of granulosa cells in follicles obtained from endometriosis patients. Serum samples were collected from 46 patients with endometriosis and from 62 patients without endometriosis who received assisted reproductive therapy. Specimens of the ovaries obtained from 10 patients with endometrioma were collected using laparoscopy. The mean serum testosterone concentration in the patients with endometriosis was significantly lower than that observed in the patients without endometriosis. Furthermore, high expression of a pro-apoptotic Bcl-2 member, BimEL, in the follicles was found to be associated with a low serum testosterone level. We clarified the underlying mechanisms using a basic approach employing human immortalized granulosa cells derived from a primary human granulosa cell tumor, the COV434 cell line. The in vitro examination demonstrated that testosterone inhibited apoptosis induced by sex steroids depletion via the PI3K/Akt-FoxO3a pathway in the COV434 cells. In conclusion, we elucidated the mechanism underlying the anti-apoptotic effects of testosterone on granulosa cells, and found that a low-testosterone status is a potentially important step in the development of premature ovarian insufficiency in patients with endometriosis. |
| first_indexed | 2024-12-16T07:38:32Z |
| format | Article |
| id | doaj.art-6b75f34ff9824238a5106adcc49586dd |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T07:38:32Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-6b75f34ff9824238a5106adcc49586dd2022-12-21T22:39:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01912e11561810.1371/journal.pone.0115618A low-testosterone state associated with endometrioma leads to the apoptosis of granulosa cells.Yoshihiro J OnoAkiko TanabeYoko NakamuraHikaru YamamotoAtsushi HayashiTomohito TanakaHiroshi SasakiMasami HayashiYoshito TeraiMasahide OhmichiAlthough endometriosis is suspected to be a cause of premature ovarian insufficiency (POI), the mechanism(s) underlying this process have not been elucidated. Recently, androgens were shown to promote oocyte maturation and to play a role in folliculogenesis. In addition, several reports have documented low testosterone levels in the follicular fluid obtained from endometriosis patients. We therefore examined whether the low levels of serum testosterone are associated with the apoptosis of granulosa cells in follicles obtained from endometriosis patients. Serum samples were collected from 46 patients with endometriosis and from 62 patients without endometriosis who received assisted reproductive therapy. Specimens of the ovaries obtained from 10 patients with endometrioma were collected using laparoscopy. The mean serum testosterone concentration in the patients with endometriosis was significantly lower than that observed in the patients without endometriosis. Furthermore, high expression of a pro-apoptotic Bcl-2 member, BimEL, in the follicles was found to be associated with a low serum testosterone level. We clarified the underlying mechanisms using a basic approach employing human immortalized granulosa cells derived from a primary human granulosa cell tumor, the COV434 cell line. The in vitro examination demonstrated that testosterone inhibited apoptosis induced by sex steroids depletion via the PI3K/Akt-FoxO3a pathway in the COV434 cells. In conclusion, we elucidated the mechanism underlying the anti-apoptotic effects of testosterone on granulosa cells, and found that a low-testosterone status is a potentially important step in the development of premature ovarian insufficiency in patients with endometriosis.http://europepmc.org/articles/PMC4275210?pdf=render |
| spellingShingle | Yoshihiro J Ono Akiko Tanabe Yoko Nakamura Hikaru Yamamoto Atsushi Hayashi Tomohito Tanaka Hiroshi Sasaki Masami Hayashi Yoshito Terai Masahide Ohmichi A low-testosterone state associated with endometrioma leads to the apoptosis of granulosa cells. PLoS ONE |
| title | A low-testosterone state associated with endometrioma leads to the apoptosis of granulosa cells. |
| title_full | A low-testosterone state associated with endometrioma leads to the apoptosis of granulosa cells. |
| title_fullStr | A low-testosterone state associated with endometrioma leads to the apoptosis of granulosa cells. |
| title_full_unstemmed | A low-testosterone state associated with endometrioma leads to the apoptosis of granulosa cells. |
| title_short | A low-testosterone state associated with endometrioma leads to the apoptosis of granulosa cells. |
| title_sort | low testosterone state associated with endometrioma leads to the apoptosis of granulosa cells |
| url | http://europepmc.org/articles/PMC4275210?pdf=render |
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