Ovarian Insufficiency: From Molecular Pathology to Novel Therapeutic Approach

Dear Colleagues,

Ovarian insufficiency represents a challenge where recent molecular discoveries revolutionized our understanding and therapeutic arsenal.

Recent molecular insights have revealed intricate mechanisms beyond traditional paradigms. Epigenetic modifications, particularly DNA methylation and histone acetylation, regulate follicular dynamics and ovarian aging. Mitochondrial dysfunction emerges as a central player in oocyte quality deterioration, while inflammasome activation and oxidative stress accelerate follicular atresia. Ovarian stem cell discovery challenges conventional dogma, and cellular senescence pathways offer therapeutic targets.

While conventional approaches—hormone replacement therapy and assisted reproductive technologies—remain foundational, emerging interventions are transforming clinical possibilities. Intraovarian regenerative therapies include platelet-rich plasma, mesenchymal and very small embryonic-like stem cells, and bioengineered ovarian tissue reconstruction. Growth hormone supplementation, mitochondrial-targeted antioxidants, NAD+ precursors, and senolytic agents address cellular senescence. Advanced techniques—in vitro maturation with stem cell co-culture, in vitro gametogenesis, and three-dimensional ovarian scaffolds—represent paradigm-shifting approaches targeting fundamental mechanisms of ovarian decline.

This Special Issue welcomes research elucidating molecular mechanisms—genetic, immunological, and metabolic—and clinical investigations of both established and experimental therapies. We seek studies that translate laboratory discoveries into evidence-based protocols, offering tangible hope for women with premature ovarian insufficiency, diminished reserve, and age-related dysfunction.

Together, we advance precision medicine in reproductive health.

Prof. Dr. Aleksandar Ljubić
Guest Editor

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