Two distinct mechanisms lead to either oocyte or spermatocyte decrease in C. elegans after whole developmental...

Area of Science:

• Environmental toxicology
• Radiation biology
• Molecular reproductive toxicology

Background:

• Wildlife faces reproductive harm from ionizing radiation (IR), impacting population dynamics.
• Reproduction is the most radiosensitive endpoint in invertebrates, necessitating understanding molecular mechanisms.
• Previous work indicated life-stage-dependent reproductive decline in Caenorhabditis elegans due to IR.

Purpose of the Study:

• To precisely identify molecular determinants of IR-induced reproductive toxicity, focusing on gamete number reduction.
• To analyze conserved molecular pathways (apoptosis, Ras/ERK) for cross-species extrapolation of radiosensitivity.
• To investigate the life-stage-dependent effects of chronic IR exposure on reproductive pathways.

Main Methods:

• Chronic exposure of Caenorhabditis elegans to 50 mGy·h-1 gamma IR during embryogenesis, gametogenesis, and full development.
• Analysis of conserved apoptosis and MAP kinase Ras/ERK (MPK-1) pathways involved in reproduction and stress responses.
• Functional analysis of apoptosis and assessment of germ cell proliferation and pathway activation.

Main Results:

• Apoptosis and Ras/ERK pathways exhibit life-stage-dependent activation, accumulating damage from chronic IR exposure.
• Ras/ERK pathway activation was observed in the gonad's pachytene region but not the ovulation zone.
• DNA-damage-induced apoptosis caused decreased ovulation rates, while sperm reduction appeared linked to germ cell proliferation speed, not apoptosis.

Conclusions:

• IR-induced reproductive toxicity in Caenorhabditis elegans is mediated by life-stage-dependent molecular pathways.
• Apoptosis drives reduced ovulation, but sperm count reduction involves other mechanisms requiring further investigation.
• Results contribute to understanding sex-specific radiosensitivity and support Adverse Outcome Pathway #396 for IR effects on populations.