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Published on: December 17, 2017
In vitro study of Withanolide D toxicity on goat preantral follicles and its effects on the cell cycle
Denise Damasceno Guerreiro1, Laritza Ferreira de Lima1, Naiza Arcângela Ribeiro de Sá1
1Faculty of Veterinary Medicine, Laboratory of Manipulation of Oocyte and Preantral Follicles (LAMOFOPA), State University of Ceara, Avenue Silas Munguba 1700, 60740-000, Fortaleza, CE, Brazil.
Abstract:
The Withanolide D is a chemotherapeutic potential against the human tumor cell. However, there is no report on the effect of this compound on ovarian function, especially on preantral folliculogenesis. The aim of this study was to evaluate the toxicity of a new candidate to anticancer drug, Withanolide D (WD) on morphologic integrity, development (activation and granulosa cell proliferation) and gene expression of ABCB1 protein of caprine preantral follicles. Ovarian fragments were cultured in vitro for 2 or 6 days in α-MEM or α-MEM added with paclitaxel (PTX -0.1 μg/mL; negative control) and different concentrations of WD (WD1.5, WD3.0 or WD6.0). The higher dose of WD showed a toxic effect similar to PTX and higher (P < 0.05) than other treatments after 2 and 6 days. In addition, WD6.0 reduced the cell proliferating compared to PTX or mild dose. The expression of ABCB1 remained unchanged in the presence of the chemotherapeutic agents (PTX and WD) throughout the culture period. In conclusion, WD exerted a toxic effect observed by decreasing follicular survival and cell proliferation, on the preantral caprine follicles similar to PTX, whose negative effect on folliculogenesis is already widely known.
Insights
Withanolide D (WD), a potential anticancer drug, showed toxicity to caprine preantral follicles, similar to paclitaxel. This compound reduced follicular survival and cell proliferation, impacting ovarian function.
Area of Science:
- Reproductive Biology
- Toxicology
- Cancer Research
Background:
- Withanolide D (WD) exhibits anticancer properties against human tumor cells.
- Limited data exists on WD's impact on ovarian function and preantral folliculogenesis.
- Understanding potential reproductive toxicity is crucial for novel anticancer drug development.
Purpose of the Study:
- To assess the toxicity of Withanolide D (WD) on caprine preantral follicles.
- To evaluate WD's effects on follicular morphology, development, and ABCB1 gene expression.
- To compare WD's toxicity with paclitaxel (PTX), a known chemotherapeutic agent.
Main Methods:
- In vitro culture of caprine ovarian fragments for 2 or 6 days.
- Treatment with varying concentrations of WD (WD1.5, WD3.0, WD6.0) and paclitaxel (PTX).
- Assessment of follicular integrity, granulosa cell proliferation, and ABCB1 gene expression.
Main Results:
- The highest WD dose (WD6.0) exhibited significant toxicity, comparable to PTX.
- WD6.0 reduced preantral follicle survival and granulosa cell proliferation.
- ABCB1 gene expression remained unaffected by both WD and PTX treatments.
Conclusions:
- Withanolide D demonstrates dose-dependent toxicity on caprine preantral follicles.
- WD negatively impacts follicular survival and proliferation, similar to paclitaxel.
- Further research is needed to explore WD's reproductive safety profile.
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