Increased rounds of gonadotropin stimulation have side effects on mouse fallopian tubes and oocytes

Area of Science:

• Reproductive Biology
• Molecular Endocrinology
• Cellular Biology

Background:

• Gonadotropin stimulation is crucial for assisted reproductive technologies.
• The impact of multiple stimulation rounds on female reproductive tissues and oocyte quality requires further investigation.
• Understanding molecular changes in fallopian tubes and oocytes is essential for optimizing fertility treatments.

Purpose of the Study:

• To investigate the effects of increased gonadotropin stimulation rounds on protein expression in mouse fallopian tubes.
• To assess the impact of gonadotropin stimulation on meiotic spindle morphology in ovulated oocytes.
• To evaluate the relationship between stimulation cycles and reproductive performance.

Main Methods:

• Adult female mice underwent 6 or 8 rounds of gonadotropin stimulation or served as controls.
• Fallopian tubes were analyzed for protein levels (Cyclin D1, p53, AKT, GSK3B, SOX2, OCT3/4, B-catenin, CHK1, H2A.X).
• Ovulated oocytes were examined for meiotic spindle morphology using anti-A/B tubulin staining.

Main Results:

• Increased Cyclin D1, p53, and phospho-p53 after 6 rounds; elevated p-AKT, p-GSK3B, p53, Cyclin D1, and OCT3/4 after 8 rounds.
• No significant changes in SOX2 or B-catenin; undetectable phospho-CHK1 and phospho-H2A.X indicated limited DNA damage.
• Significant decrease in oocyte number and normal meiotic spindle percentage from 6 rounds onwards.

Conclusions:

• Multiple gonadotropin stimulation cycles negatively impact mouse reproductive performance.
• Over-expression and activation of cell cycle regulatory proteins in fallopian tubes are induced by stimulation.
• Impaired oocyte spindle morphology contributes to reduced fertility following repeated stimulation.