Sex-Specific Effects of Pyraclostrobin Exposure on Hematopoiesis and Thymic Development in Mice 2260076

Abstract

Abstract Introduction Populations with high pesticide exposure face elevated risks of immune and hematologic disorders, yet the mechanisms remain unclear. Pyraclostrobin (PYRA), a fungicide known to disrupt mitochondrial function, may alter hematopoietic and thymic processes. We hypothesized that PYRA induces mitochondrial stress leading to immune dysregulation in a sex-dependent manner. Methods Eight-week-old C57BL/6 mice were exposed to PYRA (10—100 mg/kg b.w.) for 14 or 30 days via intraperitoneal injection. Hematologic profiles were obtained by complete blood count, while flow cytometry assessed bone marrow progenitors, thymic and splenic cell populations. Results PYRA exposure at 10 mg/kg altered T lymphocyte populations in both differently, suggesting sex-specific immune modulation. Males showed increased MPP2 and decreased MPP3 frequencies, with reduced Lin⁻c-Kit+Sca1⁻ progenitors; females exhibited decreased ST-HSCs, increased GMP%, and decreased MEP%. Thymic analysis revealed increased total thymocyte counts in males, including CD8+SP cells, while females showed selective CD8+SP increases. Conclusion PYRA disrupts hematopoietic and thymic development in a sex-dependent manner, potentially through mitochondrial dysfunction. Ongoing gene expression analysis will clarify mitochondrial—hematopoietic interactions, enhancing understanding of pesticide-induced immune and marrow failure mechanisms. Funding Source California Institute for Regenerative Medicine (EDUC5-13686) (J.O.M.); UCM Committee on Research Faculty Grant (J.O.M.); Fulbright Philippines Fellowship (M.G.R.) Topic Categories Hematopoiesis and Immune System Development (HEM)