BACKGROUND Superovulation treatment had some adverse effects on maturity and development of oocytes. Can superovulation dose of gonadotropins (Gns) affect the transcriptome of granulosa cells and follicular fluid (FF) hormone levels? METHODS One leading pre-ovulatory follicle per subject was used from three natural-cycle and four Gn-stimulated patients. Granulosa cells and FF samples were collected from the same leading follicle of each patient. RNA was extracted from granulosa cells and subjected to deep sequencing and analysis. Follicle-stimulating hormone (FSH), estradiol (E2), androstenedione (AND), testosterone (T), luteinizing hormone (LH), and progesterone (P4) levels in FF were measured by immunoassays. Student's t test was used for statistical analysis. RESULTS A total of 715 genes were up-regulated, and 287 genes were down-regulated, in the Gn-stimulated group relative to the control group. Gene Ontology analysis revealed that the down-regulated genes were enriched in cell cycle and meiosis pathways, primarily those associated with follicle or oocyte maturation and quality. On the other hand, the up-regulated genes were enriched in functions related to immunity and cytokine-cytokine receptor interactions. Compared to the follicles of natural cycle, the E2 and LH concentrations were significantly reduced (P < 0.001), the P4 concentration was significantly increased (P = 0.003), and the concentrations of FSH, T and AND had no difference in the follicles of Gn-stimulated cycle. CONCLUSIONS Cell cycle- and meiosis-associated genes were down-regulated by Gns stimulation, whereas immune- and cytokine-associated genes were up-regulated. Hormone levels were also affected by Gns stimulation. Compared with natural-cycle follicles,putative markers associated with oocyte quality and follicle maturation were significantly different from those in Gn-stimulated follicles. Hormone levels in follicles were compatible with the steroidogenic patterns of granulosa cell, which reflects the follicle maturation and oocyte quality.

中文翻译：

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外源促性腺激素对人颗粒细胞转录组和卵泡液激素谱的影响。

背景技术超排卵治疗对卵母细胞的成熟和发育有一些不利影响。促性腺激素（Gns）的超排卵剂量会影响颗粒细胞的转录组和卵泡液（FF）激素水平吗？方法从三位自然周期和四位Gn刺激的患者中使用每位受试者一个排卵前领先的卵泡。从每个患者的相同前导卵泡收集颗粒细胞和FF样品。从颗粒细胞提取RNA，并进行深度测序和分析。通过免疫测定法测定FF中的促卵泡激素（FSH），雌二醇（E2），雄烯二酮（AND），睾丸激素（T），黄体生成激素（LH）和孕激素（P4）水平。学生的t检验用于统计分析。结果共有715个基因被上调，在Gn刺激的组中，相对于对照组，有287个基因被下调。基因本体分析表明，下调的基因在细胞周期和减数分裂途径中富集，主要与卵泡或卵母细胞的成熟和质量有关。另一方面，上调的基因富含与免疫和细胞因子-细胞因子受体相互作用有关的功能。与自然周期的卵泡相比，E2和LH的浓度显着降低（P <0.001），P4的浓度显着增加（P = 0.003），而FSH，T和AND的卵泡中的卵泡没有差异。 Gn刺激的周期。结论Gns刺激下调了细胞周期和减数分裂相关的基因，而上调了免疫和细胞因子相关的基因。激素水平也受到Gns刺激的影响。与自然周期卵泡相比，与卵母细胞质量和卵泡成熟相关的标志物与Gn刺激卵泡中的标志物显着不同。卵泡中的激素水平与颗粒细胞的类固醇生成模式兼容，这反映了卵泡的成熟和卵母细胞的质量。