Cumulus Expansion and Oocyte Quality Across the Pubertal Transition in Mice: Implications for Modeling Fertility Preservation in Adolescents

Abstract Objective: To determine whether cumulus expansion and oocyte aneuploidy differ across the pubertal transition in a murine model designed to approximate clinical assisted reproductive technology (ART) conditions. Methods: Controlled experimental animal study using prepubertal (D16–25), peripubertal (D26–35), and reproductively young adult CD-1 female mice (9 and 12 weeks old). Mice underwent gonadotropin stimulation to model controlled ovarian hyperstimulation. Cumulus–oocyte complexes (COCs) were collected following in vivo maturation prior to ovulation or assessed before and after in vitro maturation (IVM). Main outcome measures included COC surface area, cumulus cell layer thickness, oocyte spindle configuration, chromosome alignment, and aneuploidy rates. Results: Following in vivo maturation, COC surface area (1505 ± 151.4 µm² vs. 1735 ± 115.7 µm² vs. 1637 ± 75.6 µm², p = 0.44), cumulus layer thickness (176 ± 18 µm vs. 201.5 ± 21.2 µm vs. 196.7 ± 13.7 µm, p = 0.59), and oocyte euploidy rates (94.25 ± 3.6% vs. 91.41 ± 4.8% vs. 88.14 ± 2.9%, p = 0.57) were similar across D21–25, D28–35, and 12-week cohorts, respectively. Under IVM conditions, pre-IVM COC area was smaller in D16–21 mice compared with 9-week mice (377.6 ± 5.6 µm² vs. 466.8 ± 16.5 µm², p < 0.05). However, post-IVM COC area, cumulus expansion, and spindle/chromosome abnormality rates did not differ among groups (all p > 0.05). Conclusion: In this murine model, markers of oocyte competence, including cumulus expansion, meiotic integrity, and aneuploidy rates, were largely preserved across the pubertal transition, highlighting translational limitations of mice for modeling human adolescent ovarian biology.