JBRA Assisted Reproduction 2025;29(Suppl.2 SBRA 2025):86
Poster Presentation
29^th Annual Congress of the SBRA. São Paulo/SP - Brazil, 2025
doi: 10.5935/1518-0557.20263666

P-74. Effects of Liraglutide on Ovarian Histomorphology in LDLr⁻/⁻ Mice on a High-Calorie Diet

Licia Cristina Silva de Lima Oliveira¹, Nara Vicente de Matos¹, Beatriz Astori Paraguassu¹, Antonio João Viana Batista¹, Tadeu Uggere de Andrade¹, Girlandia Alexandre Brasil Amorim¹, Marcella Martins Terra¹

¹ Universidade Vila Velha - UVV - Vila Velha - Espírito Santo – Brasil

Objective: To evaluate the effects of liraglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, on ovarian follicular histomorphology in low-density lipoprotein receptor knockout (LDLr⁻/⁻) mice, considering the increasing use of this drug among women of reproductive age.
Methods: Female LDLr⁻/⁻ knockout mice and their wild-type (C57BL/6) counterparts, aged 2–3 months, were randomly assigned to three groups: 1) Wild Type (WT): standard diet (Alinutri^® rodent chow) + saline (vehicle), 2) LDLr⁻/⁻ control: high-calorie diet + saline (vehicle, subcutaneous), 3) LDLr⁻/⁻ LIRA: high-calorie diet + liraglutide (Victoza^®; 1.2 mg/kg/ day, subcutaneous). The high-calorie diet (Western Diet, Pragsoluções^®) was rich in sucrose and lipids, containing 16.9% protein, 42.8% carbohydrates, 40.3% lipids, and 0.15% cholesterol. The treatment lasted 60 consecutive days. At the end of the protocol, animals were euthanized, and ovaries were collected, fixed in paraformaldehyde, and embedded in paraffin. Histological sections were stained with hematoxylin and eosin for morphological and quantitative analyses. Follicles were classified as primordial, primary, secondary, or tertiary. Follicle counts were performed on alternating sections to avoid duplication. For morphometric analysis, the area of tertiary follicles was measured using ImageJ^® software. Statistical analysis was performed using ANOVA followed by Tukey's post hoc test, with significance set at p<0.05.
Results: Histological analysis revealed no significant differences between the liraglutide and control groups regarding the total number of follicles (p>0.05). Similarly, the distribution of follicles across developmental stages—primordial, primary, secondary, and tertiary—remained comparable among groups. Ovarian morphology was preserved in all treated animals, with no evidence of degeneration or tissue toxicity. Regarding tertiary follicle area, a non-significant reduction was observed from WT to LDLr⁻/⁻ control (p=0.066). However, the LDLr⁻/⁻ LIRA group (mean=2.13) showed a statistically significant reduction compared with WT (mean=3.04; p=0.002). No significant difference was found between LDLr⁻/⁻ control and LDLr⁻/⁻ LIRA groups (p=0.415).
Conclusion: Chronic liraglutide treatment in LDLr⁻/⁻ mice did not induce significant changes in ovarian morphology or follicular distribution, suggesting preservation of tissue integrity. The reduction in tertiary follicle mean area observed between groups was not associated with relevant structural alterations. Considering the growing use of GLP-1 receptor agonists by women of reproductive age, further studies are warranted to assess potential long-term reproductive effects and to evaluate the translational relevance of these findings in clinical settings.