Post-translational modifications (PTMs) of proteins, as the core mechanism for dynamically regulating follicular development, affect the maintenance of mammalian fertility by precisely coordinating granulosa cell–oocyte interaction, metabolic reprogramming, and epigenetic remodeling. Dysregulation of these modifications directly contributes to major reproductive diseases, including polycystic ovary syndrome (PCOS) and premature ovarian insufficiency (POI). Post-translational modifications regulate follicular development through intricate mechanisms. Thus, this review systematically synthesizes recent advances in PTMs, encompassing traditional ones such as phosphorylation, ubiquitination, and acetylation, alongside emerging modifications including lactylation, SUMOylation, and ISGylation, thereby constructing a more comprehensive PTM landscape of follicular development. Furthermore, this study dissects the molecular interaction networks of these PTMs during follicular activation, maturation, and ovulation, and uncovers the common mechanisms through which PTM dysregulation contributes to pathological conditions, including hyperandrogenism in PCOS and follicular depletion in POI. Finally, this review ultimately provides a theoretical basis for improving livestock reproductive efficiency and precise intervention in clinical ovarian diseases.

Porcine reproductive and respiratory syndrome virus is a major pathogen that causes massive economic losses in the global swine industry. Lysine propionylation and malonylation are metabolism-sensitive post-translational modifications, yet their coordinated regulatory roles during PRRSV pulmonary infection remain unknown. This study combined quantitative proteomics, propionylome and malonylome to characterize host molecular alterations between healthy and PRRSV-infected porcine lung tissues (three piglets per group). Quantitative proteomics identified 1467 significantly downregulated proteins and only 129 upregulated proteins, indicating a profound host protein shutoff during PRRSV pulmonary infection. The two acyl modifications displayed opposite regulatory patterns independent of global protein expression changes: 51 propionylation sites (24 proteins) were upregulated with only 1 downregulated, while 37 malonylation sites (30 proteins) were downregulated and only 5 upregulated. Functional enrichment and PPI network analysis revealed clear functional divergence: hyper-propionylated hub proteins were exclusively enriched in mitochondrial energy metabolism pathways, whereas hypo-malonylated core proteins were mainly involved in lipid metabolism and cell fate regulation. Integrated multi-omics analysis confirmed that protein expression and lysine acylation constitute two coordinated but independent regulatory layers, with histone H4 identified as a candidate target of competitive propionylation/malonylation. This work reports the comprehensive landscape of lysine propionylation and malonylation upon PRRSV infection, reveals a dual-PTM remodeling strategy for viral hijacking of host homeostasis, and provides candidate targets for future functional investigation and antiviral development.