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在窦卵泡生长过程中,不同的卵泡刺激素暴露方案会改变小鼠卵丘-卵母细胞复合物中的基因表达。

Different follicle-stimulating hormone exposure regimens during antral follicle growth alter gene expression in the cumulus-oocyte complex in mice.

机构信息

Follicle Biology Laboratory, Vrije Universiteit Brussel, Brussels, Belgium.

出版信息

Biol Reprod. 2010 Oct;83(4):514-24. doi: 10.1095/biolreprod.109.083311. Epub 2010 Jun 30.

Abstract

Follicle-stimulating hormone (FSH) and oocyte-secreted factors influence granulosa cell differentiation and follicle development. Whereas FSH stimulates the expression of mural cell transcripts, oocyte-secreted factors regulate specific cumulus cell genes and suppress the appearance of mural cell transcripts. This study addresses the extent to which clinically relevant changes in FSH doses applied during antral follicle development in vitro could alter the expression of oocyte and cumulus cell transcripts. A 12-day culture system in which mouse ovarian preantral follicles can grow to preovulatory follicles was used. The following three FSH regimens were considered: 1) continuous exposure to an FSH level of 10 mIU/ml (control), 2) decreasing concentrations of FSH (low FSH), and 3) an FSH level of 25 mIU/ml (high FSH) as soon as the antrum is formed. Transcripts in oocytes (Gdf9, Bmp15, and Fgf8) and in cumulus cells (Amh, Lhcgr, Ar, and Pfkp) were quantified by real-time PCR. Under high FSH, the three oocyte transcripts were upregulated, while in cumulus cells a shutdown of the Amh signal and substantial increases in Lhcgr and Ar expression were measured. In contrast, low FSH tended to reduce Lhcgr to levels comparable to those in vivo. Levels of Pfkp were not affected by FSH doses. These results demonstrate that a 2.5-fold increase in FSH changes both oocyte and cumulus cell transcript levels. Conversely, a decrease in FSH does not affect transcript levels but seems to limit inappropriate Lhcgr expression. Modulating FSH within physiological ranges during the antral phase of culture alters cumulus cell differentiation.

摘要

卵泡刺激素(FSH)和卵母细胞分泌的因子影响颗粒细胞的分化和卵泡的发育。虽然 FSH 刺激壁细胞转录物的表达,但卵母细胞分泌的因子调节特定的卵丘细胞基因,并抑制壁细胞转录物的出现。本研究探讨了在体外进行窦前卵泡发育过程中,临床相关剂量的 FSH 变化对卵母细胞和卵丘细胞转录物表达的影响程度。使用了一种为期 12 天的培养系统,其中可以使小鼠卵巢前腔卵泡生长到排卵前卵泡。考虑了以下三种 FSH 方案:1)持续暴露于 10 mIU/ml 的 FSH 水平(对照),2)FSH 浓度降低(低 FSH),以及 3)一旦形成窦腔,FSH 水平为 25 mIU/ml(高 FSH)。通过实时 PCR 定量测定卵母细胞(Gdf9、Bmp15 和 Fgf8)和卵丘细胞(Amh、Lhcgr、Ar 和 Pfkp)中的转录物。在高 FSH 下,三种卵母细胞转录物上调,而在卵丘细胞中,Amh 信号关闭,Lhcgr 和 Ar 表达显著增加。相比之下,低 FSH 倾向于将 Lhcgr 降低到与体内相当的水平。Pfkp 水平不受 FSH 剂量的影响。这些结果表明,FSH 增加 2.5 倍会改变卵母细胞和卵丘细胞的转录物水平。相反,FSH 减少不会影响转录物水平,但似乎限制了不适当的 Lhcgr 表达。在培养的窦前期内调节 FSH 在生理范围内可改变卵丘细胞的分化。

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