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However, the interactions between oocytes and cumulus granulosa cells (CGs), oocytes and mural granulosa cells (MGs), and CGs and MGs remain to be fully explored. Using single-cell RNA-sequencing (scRNA-seq), we determined the transcriptional profiles of oocytes, CGs and MGs in antral follicles. Analysis of scRNA-seq data revealed that CGs may regulate follicular development through the BMP15-KITL-KIT-PI3K-ARF6 pathway with elevated expression of luteinizing hormone receptor (LHR). Because internalization of the LHR is regulated by <jats:italic>Arf6<\/jats:italic>, we constructed LHR<jats:sup>N316S<\/jats:sup> mice by CRISPR\/Cas9 to further explore mechanisms of follicular development and novel treatment strategies for female infertility. Ovaries of LHR<jats:sup>N316S<\/jats:sup> mice exhibited reduced numbers of corpora lutea and ovulation. The LHR<jats:sup>N316S<\/jats:sup> mice had a reduced rate of oocyte maturation in vitro and decreased serum progesterone levels. Mating LHR<jats:sup>N316S<\/jats:sup> female mice with ICR wild type male mice revealed that the infertility rate of LHR<jats:sup>N316S<\/jats:sup> mice was 21.4% (3\/14). Litter sizes from LHR<jats:sup>N316S<\/jats:sup> mice were smaller than those from control wild type female mice. The oocytes from LHR<jats:sup>N316S<\/jats:sup> mice had an increased rate of maturation in vitro after progesterone administration in vitro. Furthermore, progesterone treated LHR<jats:sup>N316S<\/jats:sup> mice produced offspring numbers per litter equivalent to WT mice. These findings provide key insights into cellular interactions in ovarian follicles and provide important clues for infertility treatment.<\/jats:p>\n                <jats:p><jats:bold>Graphical Abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s12539-024-00646-7","type":"journal-article","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T11:03:03Z","timestamp":1723806183000},"page":"976-989","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Luteinizing Hormone Receptor Mutation (LHRN316S) Causes Abnormal Follicular Development Revealed by Follicle Single-Cell Analysis and CRISPR\/Cas9"],"prefix":"10.1007","volume":"16","author":[{"given":"Chen","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqiang","family":"Nie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bufang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlan","family":"Mu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geng G.","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aijun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dali","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,16]]},"reference":[{"key":"646_CR1","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1139\/y10-009","volume":"88","author":"GM Kidder","year":"2010","unstructured":"Kidder GM, Vanderhyden BC (2010) Bidirectional communication between oocytes and follicle cells: ensuring oocyte developmental competence. 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