Dysregulated post-translational modifications in granulosa cells drive ovarian dysfunction and potential infertility applications (Review)

TL;DR

This review explores how changes in protein modifications in granulosa cells affect ovarian function and infertility.

Contribution

The paper highlights novel PTMs like SUMOylation and lactylation in granulosa cells and their role in infertility.

Findings

PTMs regulate granulosa cell proliferation, differentiation, and apoptosis.

Aberrant PTMs impair follicular development and contribute to infertility.

Targeting PTM-regulated signaling may offer new infertility treatments.

Abstract

Ovarian granulosa cells (GCs), as key components of follicles, orchestrate follicular development and ovarian maturation through bidirectional communication with oocytes and through hormone synthesis. Their dysfunction substantially contributes to female infertility. Post-translational modifications (PTMs) carry out pivotal roles in the regulation of ovarian physiology and pathology by modulating GC proliferation, differentiation, apoptosis and steroid hormone secretion. The present review seeks to summarize the current advances in canonical PTMs such as phosphorylation, methylation, acetylation and ubiquitination, as well as novel protein modifications such as SUMOylation and lactylation, particularly focusing on their roles in the proliferation, differentiation and apoptosis of GCs at the molecular level. Moreover, the present review explores how aberrant PTMs impair GC function, leading to follicular developmental disorders, and proposes that targeting PTM-regulated signaling in GCs may provide novel therapeutic strategies for ovarian dysfunction. Collectively, the present review aims to provide insights into elucidating the etiology of infertility, and establishing a theoretical foundation for the development of PTM-targeted reproductive interventions.

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