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.

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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