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Paclitaxel is evidence to reduce growing ovarian follicle growth in mice model study
Mila Maidarti1, Wataru Tarumi2, Seido Takae2
1Department of Obstetrics and Gynecology, Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia.
Abstract:
We aimed to investigate the effects of paclitaxel on ovarian follicle development and oocyte meiotic competence. Early secondary follicles were cultured individually with or without paclitaxel 2.5 × 10-10, 2.5 × 10-9, and 2.5 × 10-8 M for 12 days. Thereafter, the follicles were treated with human chorionic gonadotropin (hCG) and epidermal growth factor (EGF). Follicle morphology, oocytes meiotic maturation, immunofluorescence for α-tubulin of the oocytes, mRNA expression of growth differentiation factor 9 (GDF9), B-cell lymphoma 2 (Bcl2), and Bcl2-associated X (Bax) were examined every 4, 8, and 12 days of the culture period. We demonstrated that high dose paclitaxel treatment decreased follicle survival (p ≤ 0.05), while lower dose (2.5 × 10-9 M) reduced the survival compared to control after 12 days of culture. The number of oocytes at MII stage was not significantly different between control and paclitaxel groups (p > 0.05). Paclitaxel increased GDF9 expression in oocytes after 4 days of the culture (p ≤ 0.05). Bcl2 declined significantly compared to control after 8 days (p ≤ 0.05 for all groups), while Bax expression tended to be consistent (p ≥ 0.05 for all groups). To conclude, high concentration paclitaxel reduces follicle preantral follicle growth, while in lower concentration it decreases more growing follicle growth and survival.
Insights
Paclitaxel impacts ovarian follicle development. High doses reduce growth and survival, while lower doses also decrease survival, affecting ovarian health.
Area of Science:
- Reproductive Biology
- Developmental Biology
- Toxicology
Background:
- Paclitaxel is a chemotherapy drug with known reproductive toxicity.
- Ovarian follicle development is crucial for female fertility and is sensitive to environmental factors.
Purpose of the Study:
- To investigate the effects of varying paclitaxel concentrations on early secondary ovarian follicle development and oocyte meiotic competence.
- To analyze molecular changes, including gene expression and protein localization, in response to paclitaxel exposure.
Main Methods:
- Early secondary ovarian follicles were cultured individually with different paclitaxel concentrations (2.5 × 10⁻¹⁰ to 2.5 × 10⁻⁸ M) for 12 days.
- Follicle morphology, oocyte meiotic maturation (MII stage), α-tubulin immunofluorescence, and mRNA expression of GDF9, Bcl2, and Bax were assessed.
- Follicles were stimulated with human chorionic gonadotropin (hCG) and epidermal growth factor (EGF) post-culture.
Main Results:
- High-dose paclitaxel significantly decreased follicle survival (p ≤ 0.05).
- A lower dose (2.5 × 10⁻⁹ M) also reduced follicle survival compared to controls after 12 days.
- Paclitaxel increased GDF9 expression and decreased Bcl2 expression, while Bax expression remained consistent.
Conclusions:
- High paclitaxel concentrations inhibit preantral follicle growth and survival.
- Lower paclitaxel concentrations also negatively impact growing follicle survival.
- Paclitaxel exposure alters key molecular markers associated with follicle development and apoptosis.
