Table_4_Single-cell RNA-seq analysis and cell-cluster deconvolution of the human preovulatory follicular fluid cells provide insights into the pathophysiology of ovarian hyporesponse.xlsx

Reduction in responsiveness to gonadotropins or hyporesponsiveness may lead to the failure of in vitro fertilization (IVF), due to a low number of retrieved oocytes. The ovarian sensitivity index (OSI) is used to reflect the ovarian responsiveness to gonadotropin stimulation before IVF. Although introduced to clinical practice already years ago, its usefulness to predict clinical outcomes requires further research. Nevertheless, pathophysiological mechanisms of ovarian hyporesponse, along with advanced maternal age and in younger women, have not been fully elucidated. Follicles consist of multiple cell types responsible for a repertoire of biological processes including responding to pituitary gonadotropins necessary for follicle growth and oocyte maturation as well as ovulation. Encouraging evidence suggests that hyporesponse could be influenced by many contributing factors, therefore, investigating the variability of ovarian follicular cell types and their gene expression in hyporesponders is highly informative for increasing their prognosis for IVF live birth. Due to advancements in single-cell analysis technologies, the role of somatic cell populations in the development of infertility of ovarian etiology can be clarified. Here, somatic cells were collected from the fluid of preovulatory ovarian follicles of patients undergoing IVF, and RNA-seq was performed to study the associations between OSI and gene expression. We identified 12 molecular pathways differentially regulated between hypo- and normoresponder patient groups (FDR

对促性腺激素反应性降低或低反应性可能导致体外受精（IVF）失败，原因在于回收的卵母细胞数量不足。卵巢敏感性指数（OSI）被用于反映IVF前卵巢对促性腺激素刺激的反应性。尽管其已引入临床实践多年，但其预测临床结果的有用性仍需进一步研究。尽管如此，卵巢低反应的病理生理机制，以及随着年龄增长及年轻女性中尚未得到充分阐明。卵泡由多种细胞类型组成，这些细胞类型负责一系列生物学过程，包括对垂体促性腺激素的反应，这对于卵泡生长、卵母细胞成熟及排卵至关重要。有鼓舞人心的证据表明，低反应性可能受到许多影响因素的影响，因此，研究卵巢卵泡细胞类型的变异性及其在低反应性个体中的基因表达，对于提高IVF活产预后具有重要意义。随着单细胞分析技术的进步，可以阐明体细胞种群在卵巢源性不孕症发展中的作用。在此，我们从接受IVF的患者排卵前卵泡液中收集体细胞，并进行了RNA测序，以研究OSI与基因表达之间的关联。我们确定了在低反应性和正常反应性患者组之间差异调节的12个分子通路（FDR