The follicle-deplete mouse ovary produces androgen
The follicle-deplete mouse ovary produces androgen
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DOI：
10.1095/biolreprod.103.016113
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发表时间：
2004-07-01
影响因子：
3.6
通讯作者：
Hoyer, PB
中科院分区：
文献类型：
--
作者：
Mayer, LP;Devine, PJ;Hoyer, PB
绝经后卵巢中卵泡耗尽，富含产生雄激素的间质细胞。本研究旨在使用工业化学品 4-乙烯基环己烯二环氧化物 (VCD) 引起小鼠卵泡耗竭，并表征残留卵巢组织中细胞的类固醇生成能力。根据剂量探索研究，VCD 的最佳每日浓度确定为 160 mg/kg。雌性 B6C3F(1) 未成熟小鼠每天用载体对照或 VCD（160 mg kg(-1) 天(-1)，15 天，腹腔注射）治疗。取出卵巢并进行处理以进行组织学评估。治疗开始后第 15 天，原始卵泡耗尽，初级卵泡减少至对照的 10% 左右。第 46 天，初级卵泡耗尽，次级卵泡和窦卵泡分别减少至对照的 0.7% 和 2.6%。 75% 的接受治疗的小鼠表现出动情周期紊乱。到第 58 天，所有治疗小鼠均处于持续发情间期（无周期）。第 37 天，血浆 FSH 水平相对于对照组有所增加（P < 0.05），并在第 100 天达到稳定水平。到第 127 天，相对于年龄匹配的周期对照组，VCD 治疗小鼠的显着差异包括卵巢和子宫重量减轻、血浆 LH 和 FSH 升高、血浆黄体酮和雄烯二酮降低。此外，血浆17β-雌二醇水平检测不到。与对照不同，LH 受体和高密度脂蛋白受体 (SR-BI) 的免疫染色在 VCD 治疗动物的卵巢切片中呈扩散状态。将来自第120天对照和VCD处理的动物的卵巢分离并将分散的细胞置于培养物中。来自 VCD 处理动物卵巢的培养细胞比对照细胞产生更少的 LH 刺激黄体酮。在周期性对照动物的细胞中检测不到雄烯二酮的产生。相反，经 VCD 处理的动物细胞产生的雄烯二酮在胰岛素和 LH（1 和 3 ng/ml）存在下翻倍。总的来说，这些数据表明，VCD 介导的卵泡耗竭导致残留卵巢组织，这可能类似于绝经后卵巢的滤泡耗竭。这可能作为一个有用的动物模型来检查女性随着卵巢衰老发生的卵泡丧失的动态。
The follicle-depleted postmenopausal ovary is enriched in interstitial cells that produce androgens. This study was designed to cause follicle depletion in mice using the industrial chemical, 4-vinylcyclohexene diepoxide (VCD), and characterize the steroidogenic capacity of cells in the residual ovarian tissue. From a dose-finding study, the optimal daily concentration of VCD was determined to be 160 mg/kg. Female B6C3F(1) immature mice were treated daily with vehicle control or VCD (160 mg kg(-1) day(-1), 15 days, i.p.). Ovaries were removed and processed for histological evaluation. On Day 15 following onset of treatment, primordial follicles were depleted and primary follicles were reduced to about 10% of controls. On Day 46, primary follicles were depleted and secondary and antral follicles were reduced to 0.7% and 2.6% of control, respectively. Seventy-five percent of treated mice displayed disruptions in estrous cyclicity. All treated mice were in persistent diestrus (acyclic) by Day 58. Plasma FSH levels were increased (P < 0.05) relative to controls on Day 37 and had plateaued by Day 100. Relative to age-matched cyclic controls, by Day 127, the significant differences in VCD-treated mice included reduced ovarian and uterine weights, elevated plasma LH and FSH, and reduced plasma progesterone and androstenedione. Furthermore, plasma 17beta-estradiol levels were nondetectable. Unlike controls, immunostaining for LH receptor, and the high density lipoprotein receptor (SR-BI), was diffuse in ovarian sections from VCD-treated animals. Ovaries from Day 120 control and VCD-treated animals were dissociated and dispersed cells were placed in culture. Cultured cells from ovaries of VCD-treated animals produced less LH-stimulated progesterone than control cells. Androstenedione production was nondetectable in cells from cyclic control animals. Conversely, cells from VCD-treated animals produced androstenedione that was doubled in the presence of insulin and LH (1 and 3 ng/ml). Collectively, these data demonstrate that VCD-mediated follicle depletion results in residual ovarian tissue that may be analogous to the follicle-deplete postmenopausal ovary. This may serve as a useful animal model to examine the dynamics of follicle loss in women as ovarian senescence ensues.