Reduced insulin/IGF-1 signaling extends reproductive span through somatic gonadal collagen-mediated maintenance of oocyte and embryo quality in Caenorhabditis elegans.

backgroundThe 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.

methodsWe 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.

resultsSeveral 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.

conclusionOur 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.