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Characterization of cyclicity and hormonal profile with impending ovarian failure in a novel chemical-induced mouse model of perimenopause

机译:在围绝经的新型化学诱导小鼠模型中表征周期和激素水平以及即将发生的卵巢衰竭

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4-Vinylcyclohexene diepoxide (VCD) causes early, gradual ovarian failure in mice because it specifically targets small pre-antral ovarian follicles. The period between loss of these follicles and ovarian failure is analogous to perimenopause in women. We sought to characterize the period of onset of ovarian failure in VCD-treated mice in regard to estrous cycle length and hormonal changes. Female C57Bl/6 mice (age, 28 days) were dosed daily for 15 days with VCD (160 mg/kg intraperitoneally) to cause early ovarian failure or with vehicle only (control animals). Cycle length was monitored by vaginal cytology. Plasma levels of 17beta-estradiol (E2), progesterone (P4), and follicle-stimulating hormone (FSH) in control and VCD-treated animals were measured during proestrus of cycles 1 through 12. Cycle length (mean, 5.8 days) did not differ between groups for cycles 1 through 4. In contrast, cycle length during cycles 5 through 12 was increased (mean length, 10.9 days; P < 0.05 versus control) in VCD-treated animals, which also showed an apparent increase in plasma FSH levels. Plasma E2 and P4 at proestrus did not differ between groups during any cycle. Ovarian failure in VCD-treated mice was confirmed by histological evaluation on day 156 after onset of dosing, whereas control animals were still cycling. Therefore, despite compromised cycle length in VCD-treated mice, peak ovarian steroid production in preovulatory follicles at proestrus is adequate. These results demonstrate that the VCD-treated mouse can serve as an appropriate model to mimic hormonal changes during the perimenopausal transition in women.
机译:4-乙烯基环己烯二环氧化合物(VCD)会在小鼠中引起早期的渐进性卵巢衰竭,因为它专门针对较小的前肛门前卵泡。这些卵泡丧失与卵巢功能衰竭之间的时期类似于女性的围绝经期。我们试图就动情周期长度和荷尔蒙变化来表征VCD治疗小鼠的卵巢衰竭发作期。每天给雌性C57Bl / 6小鼠(年龄28天)给药VCD(腹膜内160 mg / kg),持续15天,以引起早期卵巢衰竭或仅用赋形剂(对照组)。通过阴道细胞学监测周期长度。在第1到第12周期的发情期中测量了对照组和VCD处理的动物的17β-雌二醇(E2),孕酮(P4)和促卵泡激素(FSH)的血浆水平。未检测到周期长度(平均5.8天)周期1至4的组之间存在差异。相反,在VCD处理的动物中,周期5至12的周期长度增加了(平均长度,为10.9天;与对照组相比,P <0.05),这也表明血浆FSH水平明显增加。在任何周期中,两组之间的发情期血浆E2和P4均无差异。在开始给药后第156天,通过组织学评估证实了用VCD治疗的小鼠的卵巢衰竭,而对照动物仍在循环。因此,尽管用VCD处理的小鼠的周期长受到损害,但在发情期排卵前卵泡中卵巢类固醇的峰值产量仍然足够。这些结果表明,经VCD处理的小鼠可以作为模仿女性围绝经期过渡期荷尔蒙变化的合适模型。

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