Reduced insulin/IGF-1 signaling extends reproductive span through somatic gonadal collagen-mediated maintenance of oocyte and embryo quality in Caenorhabditis elegans.
5 affiliations
- 1Department of Reproductive Biology, All India Institute of Medical Sciences, New Delhi, 110029, India.
- 2Duke Molecular Physiology Institute, 300 North Duke Street, Durham, NC, 27701, USA.
- 3Division of Neuroscience and Ageing Biology, CSIR-Central Drug Research Institute, Lucknow, 226031, India.
- 4Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
- 5Department of Reproductive Biology, All India Institute of Medical Sciences, New Delhi, 110029, India. [email protected].
Abstract
Background
The somatic gonad plays a central role in supporting germline development and maintaining oocyte and embryonic integrity, both of which are essential for sustained reproductive function. With age, deterioration of somatic gonadal structures compromises germline support, leading to declines in oocyte morphology and increased embryonic abnormalities. The insulin/IGF-1 signaling (IIS) pathway regulates longevity and reproductive aging, and its reduction (rIIS) in the daf-2(e1370) mutant extends reproductive span in Caenorhabditis elegans. While prior work has largely focused on germline stem cells and oocyte maturation, the molecular mechanisms by which IIS preserves somatic gonadal architecture and thereby maintains oocyte and embryonic morphological integrity remain poorly understood. Elucidating how reduced IIS influences the somatic gonad can provide insights into the coordination of systemic aging pathways with tissue-specific mechanisms that sustain reproductive health.Methods
We identified somatic gonad-enriched genes from temporal transcriptomic datasets of reduced IIS animals, highlighting collagens consistently upregulated with age. Using RNAi knockdowns in both systemic and somatic gonad-specific RNAi-sensitive strains of Caenorhabditis elegans, we examined effects on self-reproductive span, oocyte and embryonic morphology, and somatic gonad integrity. Age-associated morphological changes were assessed by differential interference contrast microscopy, and regulatory dependencies were tested via quantitative polymerase chain reaction following knockdown of key transcription factors.Results
Several collagens were found to be essential for maintaining somatic gonadal architecture and preserving oocyte morphology during aging. Gonad-specific knockdown of these collagens caused structural deterioration, impaired oocyte and embryo quality, and accelerated reproductive decline. These defects occurred without a major reduction in total progeny number, suggesting that age-related reproductive loss arises primarily from tissue deterioration rather than immediate fertility impairment. Expression and function of these collagens were largely dependent on key transcription factors downstream of IIS.Conclusion
Our findings uncover a previously unrecognized role for somatic gonadal collagens in preserving reproductive function under IIS. By maintaining gonadal architecture and sustaining oocyte and embryonic morphological integrity, these collagens act as downstream effectors of IIS-mediated reproductive longevity. Targeting gonadal collagen networks may therefore represent a potential strategy to mitigate age-related reproductive decline and warrants further investigation in higher-order models.
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BibTeX
@article{kaushik2026reduced,
title = {{Reduced insulin/IGF-1 signaling extends reproductive span through somatic gonadal collagen-mediated maintenance of oocyte and embryo quality in Caenorhabditis elegans.}},
author = {Neha Kaushik and Soumya Rastogi and Vaibhav Jain and Sonia Verma and Deepak Pandey and Mona Sharma and Ashutosh Halder and Simon Gregory and Neeraj Kumar},
journal = {Cell communication and signaling : CCS},
year = {2026},
month = jul,
doi = {10.1186/s12964-026-03069-7},
url = {https://europepmc.org/article/MED/42894217},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Reduced insulin/IGF-1 signaling extends reproductive span through somatic gonadal collagen-mediated maintenance of oocyte and embryo quality in Caenorhabditis elegans.
AU - Neha Kaushik
AU - Soumya Rastogi
AU - Vaibhav Jain
AU - Sonia Verma
AU - Deepak Pandey
AU - Mona Sharma
AU - Ashutosh Halder
AU - Simon Gregory
AU - Neeraj Kumar
PY - 2026
DA - 2026/07/01
JO - Cell communication and signaling : CCS
DO - 10.1186/s12964-026-03069-7
UR - https://europepmc.org/article/MED/42894217
AB - Background The somatic gonad plays a central role in supporting germline development and maintaining oocyte and embryonic integrity, both of which are essential for sustained reproductive function. With age, deterioration of somatic gonadal structures compromises germline support, leading to declines in oocyte morphology and increased embryonic abnormalities. The insulin/IGF-1 signaling (IIS) pathway regulates longevity and reproductive aging, and its reduction (rIIS) in the daf-2(e1370) mutant extends reproductive span in Caenorhabditis elegans. While prior work has largely focused on germline stem cells and oocyte maturation, the molecular mechanisms by which IIS preserves somatic gonadal architecture and thereby maintains oocyte and embryonic morphological integrity remain poorly understood. Elucidating how reduced IIS influences the somatic gonad can provide insights into the coordination of systemic aging pathways with tissue-specific mechanisms that sustain reproductive health.Methods We identified somatic gonad-enriched genes from temporal transcriptomic datasets of reduced IIS animals, highlighting collagens consistently upregulated with age. Using RNAi knockdowns in both systemic and somatic gonad-specific RNAi-sensitive strains of Caenorhabditis elegans, we examined effects on self-reproductive span, oocyte and embryonic morphology, and somatic gonad integrity. Age-associated morphological changes were assessed by differential interference contrast microscopy, and regulatory dependencies were tested via quantitative polymerase chain reaction following knockdown of key transcription factors.Results Several collagens were found to be essential for maintaining somatic gonadal architecture and preserving oocyte morphology during aging. Gonad-specific knockdown of these collagens caused structural deterioration, impaired oocyte and embryo quality, and accelerated reproductive decline. These defects occurred without a major reduction in total progeny number, suggesting that age-related reproductive loss arises primarily from tissue deterioration rather than immediate fertility impairment. Expression and function of these collagens were largely dependent on key transcription factors downstream of IIS.Conclusion Our findings uncover a previously unrecognized role for somatic gonadal collagens in preserving reproductive function under IIS. By maintaining gonadal architecture and sustaining oocyte and embryonic morphological integrity, these collagens act as downstream effectors of IIS-mediated reproductive longevity. Targeting gonadal collagen networks may therefore represent a potential strategy to mitigate age-related reproductive decline and warrants further investigation in higher-order models.
SN - 1478-811X
ER -