Research progress on the roles of primary cilia in fertility

Primary cilia are microtubule-based organelles that project from the cell surface. They are present in cells from single-celled eukaryotes to vertebrates, including humans. Recent studies have found that primary cilia are also widely distributed in multiple organs and tissues of the reproductive system, where they influence reproductive function by directly participating in or indirectly regulating related signaling pathways, thereby affecting fertility. Primary cilia participate in the regulation of oocyte meiosis and development. They also influence sperm maturation by regulating the homeostatic microenvironment required for spermiogenesis. By mediating Hedgehog (Hh) and Wnt signaling pathways, primary cilia regulate endometrial receptivity and decidual response, thereby influencing the embryo implantation rate. Furthermore, primary cilia control migration, invasion, differentiation, and vascular remodeling of human chorionic villi mesenchymal stromal cells and trophoblasts. Structural or functional impairment of primary cilia may disrupt placental vascular remodeling, leading to placental hypoplasia, potentially through the downregulation of downstream target genes of the Hh signaling pathway. Moreover, primary cilia may be involved in ovarian aging, ovulation, and endocrine function. This article reviews the research progress on the relationship between primary cilia and fertility, explores the potential mechanisms underlying the roles of primary cilia in gamete development, endometrial receptivity, decidualization, placental development, and ovarian reproductive endocrine function, aiming to provide new insights for fertility preservation and the prevention and treatment of human reproductive disorders.