Problem This study aimed to identify subsets of regulatory T cells (Tregs) associated with ovarian aging and determine whether they can be used as markers of reproductive aging. Method This prospective cohort study was conducted among women of reproductive age. Basic physiological characteristics, reproductive hormones, Treg cell subsets, and correlations between these parameters were assessed. The POSEIDON criteria was used to identify women with low reproductive potential. Results The percentages of HLA‐DR+ CD45RAˉ Tregs and CD28ˉ Treg‐like cells significantly increased with age. Women between 40 and 49 years had significantly higher percentages of HLA‐DR+ CD45RAˉ Tregs and CD28ˉ Treg‐like cells than those at 20–29, 30–34, and 35–39 years old. Age positively correlated with FSH levels and the percentages of HLA‐DR+ CD45RAˉ Tregs and CD28ˉ Treg‐like cells, but inversely correlated with antral follicle count (AFC) and AMH levels. Interestingly, a positive correlation was found between the percentages of HLA‐DR+ CD45RAˉ Tregs and FSH levels, whereas an inverse correlation was found between those of HLA‐DR+ CD45RAˉ Tregs and AFC or AMH levels. Furthermore, a significant positive correlation was observed between the percentages of CD28ˉ Treg‐like cells and AFC. Based on POSEIDON criteria, women with the percentages of HLA‐DR+ CD45RAˉ Tregs and CD28ˉ Treg‐like cells above reference value ranges were assigned to the low prognosis groups. Conclusion These findings suggest that HLA‐DR+ CD45RAˉ Tregs and CD28ˉ Treg‐like cells can be used as immunologic markers of reproductive aging, which helps clinicians identify women with low reproductive potential and establish individualized therapeutic strategies.

During pregnancy, cell senescence at the maternal-fetal interface is required for maternal well-being, placental development, and fetal growth. However, recent reports have shown that aberrant cell senescence is associated with multiple pregnancy-associated abnormalities, such as preeclampsia, fetal growth restrictions, recurrent pregnancy loss, and preterm birth. Therefore, the role and impact of cell senescence during pregnancy requires further comprehension. In this review, we discuss the principal role of cell senescence at the maternal-fetal interface, emphasizing its “bright side” during decidualization, placentation, and parturition. Additionally, we highlight the impact of its deregulation and how this “dark side” promotes pregnancy-associated abnormalities. Furthermore, we discuss novel and less invasive therapeutic practices associated with the modulation of cell senescence during pregnancy.