Department of Life and Environmental Sciences, Università Politecnica delle Marche, Via Brecce Bianche, 60131 Ancona, Italy.
Clinica Ostetrica Ginecologica, Università Politecnica delle Marche, Ospedale G. Salesi, Via F. Corridoni 11, 60131 Ancona, Italy.
Int J Mol Sci. 2022 Feb 2;23(3):1713. doi: 10.3390/ijms23031713.
The oocyte and the surrounding cumulus cells (CCs) are deeply linked by a complex bidirectional cross-talk. In this light, the molecular analysis of the CCs is nowadays considered to be precious in providing information on oocyte quality. It is now clear that miRNAs play a key role in several ovarian functions, such as folliculogenesis, steroidogenesis, and ovulation. Thus, in this study, specific miRNAs, together with their target genes, were selected and investigated in CCs to assess the response of patients with normal (NR) and low (LR) ovarian reserve to two different controlled ovarian stimulation (COS) protocols, based on rFSH and hMG. Moreover, a Fourier transform infrared microspectroscopy (FTIRM) analysis was performed to evaluate DNA conformational changes in CCs and to relate them with the two COS protocols. The results evidenced a modulation of the expression of miRNAs and related target genes involved in CCs' proliferation, in vasculogenesis, angiogenesis, genomic integrity, and oocyte quality, with different effects according to the ovarian reserve of patients. Moreover, the COS protocols determined differences in DNA conformation and the methylation state. In particular, the results clearly showed that treatment with rFSH is the most appropriate in NR patients with normal ovarian reserve, while treatment with hMG appears to be the most suitable in LR patients with low ovarian reserve.
卵母细胞与周围的卵丘细胞（CCs）通过复杂的双向交流紧密相连。鉴于此，目前认为对 CCs 的分子分析可以为卵母细胞质量提供有价值的信息。现在已经清楚，miRNAs 在几种卵巢功能中起着关键作用，例如卵泡发生、类固醇生成和排卵。因此，在这项研究中，选择并研究了特定的 miRNAs 及其靶基因，以评估具有正常（NR）和低（LR）卵巢储备的患者对基于 rFSH 和 hMG 的两种不同控制性卵巢刺激（COS）方案的反应。此外，还进行了傅里叶变换红外微光谱（FTIRM）分析，以评估 CCs 中的 DNA 构象变化，并将其与两种 COS 方案相关联。结果表明，miRNAs 和相关靶基因的表达受到了调节，这些基因参与 CCs 的增殖、血管生成、血管生成、基因组完整性和卵母细胞质量，其作用根据患者的卵巢储备情况而有所不同。此外，COS 方案还确定了 DNA 构象和甲基化状态的差异。特别是，结果清楚地表明，对于具有正常卵巢储备的 NR 患者，rFSH 的治疗最为合适，而对于具有低卵巢储备的 LR 患者，hMG 的治疗似乎更为合适。
