Gonadotropin treatment augments postnatal oogenesis and primordial follicle assembly in adult mouse ovaries?

Gonadotropin treatment augments postnatal oogenesis and primordial follicle assembly in adult mouse ovaries?
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DOI:
10.1186/1757-2215-5-32
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发表时间:
2012-11-07
影响因子:
4
通讯作者:
Modak H
Modak H
中科院分区:
医学3区
文献类型:
--
作者:
Bhartiya D;Sriraman K;Gunjal P;Modak H

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卵泡刺激素 (FSH) 对卵巢和睾丸中的种系和体细胞室发挥作用,尽管 FSH 受体 (FSHR) 仅定位于体细胞,即生长中的卵泡的颗粒细胞和曲细精管中的支持细胞。女性高水平的FSH与卵巢储备功能差、卵巢过度刺激综合征等有关,同时FSH在卵巢皮质条体外器官型培养过程中充当生存因子。因此,进一步了解 FSH 对卵巢的作用至关重要。我们之前曾报道过,在包括小鼠、兔、猴、羊和人类在内的各种哺乳动物的卵巢表面上皮 (OSE) 中,存在多能极小胚胎样干细胞(VSEL 表达 Oct-4A 以及其他多能标记)及其直系后代“祖细胞”卵巢生殖干细胞(OGSC 表达 Oct-4B 以及其他生殖细胞标记)。本研究旨在探讨妊娠马血清促性腺激素 (PMSG) 对成年小鼠卵巢的影响,重点是 VSEL、OGSC、产后卵子发生和原始卵泡组装。在发情周期的不同阶段以及 PMSG (5 IU) 治疗 2 和 7 天后收集成年小鼠的卵巢,以研究 FSHR、多能干细胞、减数分裂和生殖细胞特异性标记物的组织结构和表达。 PMSG 治疗导致 FSHR 和增殖增加,除了大窦卵泡的颗粒细胞外,OSE 和原始卵泡 (PF) 卵母细胞的 FSHR 和 PCNA 免疫染色也增加。在 PMSG 治疗后,对照卵巢中发情期 PF 队列中总是与 PF 相关的多层 OSE 的小 1-2 个区域增加到 5-8 个区域。这与多能转录物(Oct-4A、Nanog)、减数分裂(Scp-3)和生殖细胞(Oct-4B、Mvh)特异性标记物的增加有关。 MVH 在生殖细胞巢状簇上显示出阳性免疫染色,并且在原始卵泡似乎通过卵母细胞连接的地方。本研究的结果表明,对成年小鼠进行促性腺激素 (PMSG) 治疗会导致卵巢中多能干细胞活性增加,这与减数分裂增加、多个 PF 群体的出现及其在 OSE 附近的组装有关。研究发现,这与 PF 中生殖细胞巢的存在和卵母细胞的细胞质连续性有关。我们之前报道过,成年哺乳动物卵巢中的多能卵巢干细胞是 VSEL,它产生轻微分化的 OGSC。因此,我们提出促性腺激素通过其对多能 VSEL 的作用增强成年小鼠卵巢中的新生卵子发生和 PF 组装。
Follicle stimulating hormone (FSH) exerts action on both germline and somatic compartment in both ovary and testis although FSH receptors (FSHR) are localized only on the somatic cells namely granulosa cells of growing follicles and Sertoli cells in the seminiferous tubules. High levels of FSH in females are associated with poor ovarian reserve, ovarian hyper stimulation syndrome etc. and at the same time FSH acts as a survival factor during in vitro organotypic culture of ovarian cortical strips. Thus a further understanding of FSH action on the ovary is essential. We have earlier reported presence of pluripotent very small embryonic-like stem cells (VSELs express Oct-4A in addition to other pluripotent markers) and their immediate descendants ‘progenitors’ ovarian germ stem cells (OGSCs express Oct-4B in addition to other germ cell markers) in ovarian surface epithelium (OSE) in various mammalian species including mice, rabbit, monkey, sheep and human. Present study was undertaken to investigate the effect of pregnant mare serum gonadotropin (PMSG) on adult mice ovaries with a focus on VSELs, OGSCs, postnatal oogenesis and primordial follicle assembly. Ovaries were collected from adult mice during different stages of estrus cycle and after 2 and 7 days of PMSG (5 IU) treatment to study histo-architecture and expression for FSHR, pluripotent stem cells , meiosis and germ cell specific markers. PMSG treatment resulted in increased FSHR and proliferation as indicated by increased FSHR and PCNA immunostaining in OSE and oocytes of primordial follicles (PF) besides the granulosa cells of large antral follicles. Small 1–2 regions of multilayered OSE invariably associated with a cohort of PF during estrus stage in control ovary were increased to 5–8 regions after PMSG treatment. This was associated with an increase in pluripotent transcripts (Oct-4A, Nanog), meiosis (Scp-3) and germ cells (Oct-4B, Mvh) specific markers. MVH showed positive immuno staining on germ cell nest-like clusters and at places primordial follicles appeared connected through oocytes. The results of the present study show that gonadotropin (PMSG) treatment to adult mouse leads to increased pluripotent stem cell activity in the ovaries, associated with increased meiosis, appearance of several cohorts of PF and their assembly in close proximity of OSE. This was found associated with the presence of germ cell nests and cytoplasmic continuity of oocytes in PF. We have earlier reported that pluripotent ovarian stem cells in the adult mammalian ovary are the VSELs which give rise to slightly differentiated OGSCs. Thus we propose that gonadotropin through its action on pluripotent VSELs augments neo-oogenesis and PF assembly in adult mouse ovaries.
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发表时间: 2008-03-01
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影响因子: 4.3
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发表时间: 1986-05-01
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DOI: 10.1089/scd.2011.0554
发表时间: 2012-03-01
影响因子: 4
作者:
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DOI: 10.1093/humrep/der145
发表时间: 2011-08-01
期刊: HUMAN REPRODUCTION
影响因子: 6.1
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