A low-testosterone state associated with endometrioma leads to the apoptosis of granulosa cells.
A low-testosterone state associated with endometrioma leads to the apoptosis of granulosa cells.
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DOI：
10.1371/journal.pone.0115618
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ohmichi M
中科院分区：
文献类型：
--
作者：
Ono YJ;Tanabe A;Nakamura Y;Yamamoto H;Hayashi A;Tanaka T;Sasaki H;Hayashi M;Terai Y;Ohmichi M
虽然子宫内膜异位症被怀疑是卵巢功能不全(POI)的一个原因，但这一过程背后的机制(S)尚未阐明。近年来，雄激素被证明能促进卵母细胞成熟，并在卵泡发生中发挥作用。此外，有几份报告证明，子宫内膜异位症患者卵泡液中的睾酮水平较低。因此，我们研究了低水平的血清睾酮是否与子宫内膜异位症患者卵泡颗粒细胞的凋亡有关。采集46例子宫内膜异位症患者和62例接受辅助生殖治疗的非子宫内膜异位症患者的血清标本。收集10例子宫内膜异位症患者的卵巢标本。子宫内膜异位症患者的平均血清睾酮水平明显低于非子宫内膜异位症患者。此外，在卵泡中高表达促凋亡的BimEL成员BimEL与低血清睾酮水平有关。我们使用一种基本的方法阐明了潜在的机制，该方法使用的是来自原发的人类颗粒细胞瘤COV434细胞系的人类永生化颗粒细胞。体外实验表明，睾酮通过PI3K/Akt-FOXO3a途径抑制性激素缺乏诱导的COV434细胞凋亡。总之，我们阐明了睾酮对颗粒细胞的抗凋亡作用的机制，并发现低睾酮状态是子宫内膜异位症患者卵巢功能不全发生的潜在重要步骤。
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.
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
2.7
作者：
EPPIG, JJ;FRETER, RR;SCHULTZ, RM
通讯作者：
SCHULTZ, RM
影响因子：
8
作者：
Essafi, A;de Mattos, SF;Lam, EWF
通讯作者：
Lam, EWF
DOI：
10.1016/s0889-8545(05)70302-8
发表时间：
1997-06-01
影响因子：
3.2
作者：
Eskenazi, B;Warner, ML
通讯作者：
Warner, ML
影响因子：
--
作者：
Gill, A;Jamnongjit, M;Hammes, SR
通讯作者：
Hammes, SR