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Author Spotlight: Understanding DNA Damage Response in Mammalian Oocytes and Preimplantation Embryos
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Author Spotlight: Understanding DNA Damage Response in Mammalian Oocytes and Preimplantation Embryos

Published on: June 23, 2023

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DNA damage signals from somatic uterine tissue arrest oogenesis through activated DAF-16

Gautam Chandra Sarkar1, Umanshi Rautela1, Anita Goyala1

  • 1Molecular Aging Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.

Development (Cambridge, England)
|August 14, 2023
PubMed

Insights

Somatic DNA damage disrupts germ line development when insulin signaling is low. The FOXO/DAF-16 pathway enforces strict quality control, arresting oogenesis to ensure progeny fitness.

Area of Science:

  • Cellular and Developmental Biology
  • Genetics and Genomics
  • Reproductive Biology

Background:

  • Germ line integrity is vital for offspring health.
  • The DNA damage response (DDR) protects germ cells from genotoxic stress.
  • Cell-non-autonomous quality control mechanisms in the germ line are less understood.

Purpose of the Study:

  • To investigate how somatic DNA damage affects germ line quality non-autonomously.
  • To elucidate the role of insulin/IGF-1 signaling (IIS) and FOXO/DAF-16 in this process.
  • To identify molecular pathways linking somatic DDR to germ line regulation.

Main Methods:

  • Utilized the model organism Caenorhabditis elegans.
  • Manipulated DNA damage response (DDR) and insulin/IGF-1 signaling (IIS) in specific tissues (uterus).
  • Analyzed oogenesis progression, germ cell quality, and gene expression (FOXO/DAF-16, ERK/MPK-1).

Main Results:

  • Disruption of DDR in the uterus during low IIS arrests oogenesis at the pachytene stage.
  • This arrest is dependent on the transcription factor FOXO/DAF-16.
  • Loss of FOXO/DAF-16 function in low IIS conditions leads to the production of low-quality oocytes.
  • Activated FOXO/DAF-16 suppresses ERK/MPK-1 signaling, promoting germ line arrest.

Conclusions:

  • Activated FOXO/DAF-16 acts as a surveillance mechanism sensing DDR perturbations during low IIS.
  • This pathway imposes strict quality control on oogenesis, ensuring germ cell quality and progeny fitness.
  • Identified a novel role for FOXO/DAF-16 in mediating non-autonomous germ line quality control in response to somatic DNA damage.
Keywords:
DNA damage responseFOXO/DAF-16Germ lineInsulin signalingPachytene arrest

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