Advances in understanding palmitoylation in female reproductive disorders: Mechanisms and future directions

Protein palmitoylation modification is a key lipidated post-translational modification that dynamically regulates protein function, subcellular localization, and signaling pathways in eukaryotic cells, with important implications for the onset and progression of female reproductive disorders. This article reviews the research progress of protein palmitoylation modification in the female reproductive system, focusing on its mechanisms of action in reproductive pathological processes such as polycystic ovary syndrome (PCOS), oocyte ageing and dysfunction, recurrent pregnancy loss, uterine leiomyoma, adenomyosis, and ovarian cancer. For example, it has been found that in PCOS, abnormal palmitoylation modifications lead to reduced conversion of androgens to estrogens, triggering hyperandrogenism. Palmitoylation modifications regulate the subcellular localization and function of key proteins, which in turn affect oocyte maturation and ageing. In recurrent miscarriages, aberrant palmitoylation regulation of T cell immunoglobulin domain and mucin domain-3 (Tim-3) in metaphase CD4 + T cells leads to immunomodulatory imbalance. Estrogen is involved in the development of adenomyopathy of the uterus by influencing the membrane localization of the cellular polarity protein Scribble through the acyl protein thioesterase 1/2 (APT1/APT2)-mediated process of S-palmitoylation. However, the study of palmitoylation modification in female reproductive medicine is still in its infancy. In the future, we need to further broaden the disease spectrum, integrate multi-omics technologies, and systematically analyze the spatial and temporal specificity maps of palmitoylation modification in the female reproductive system, so as to provide a new strategy for the precise diagnosis and treatment of female reproductive disorders.