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Topic

Transcriptional Impact of Glucose Enrichment on Caenorhabditis elegans oocytes

Department of Biology

Date & location

• Thursday, March 26, 2026
• 10:30 A.M.
• David Strong Building, Room C124

Examining Committee

Supervisory Committee

• Dr. Nicole Templeman, Department of Biology, ̽��ϵ�� (Supervisor)
• Dr. Greg Owens, Department of Biology, UVic (Member)
• Dr. Caren Helbing, Department of Biochemistry and Microbiology, UVic (Outside Member)

External Examiner

• Dr. Leigh Anne Swayne, School of Medical Sciences, UVic

Chair of Oral Examination

• Dr. Aditya Mojumdar, Department of Biochemistry and Microbiology, UVic

Abstract

Reproductive aging in biological females is driven by a decline in oocyte quality, a process accelerated by metabolic stress such as high dietary glucose. The insulin/insulin-like growth factor-1 (IIS) pathway is a key nutrient-sensing regulator, and in C. elegans, reduced IIS via the daf-2(e1370) reduction-of-function mutation protects against glucose-induced reproductive decline. To uncover the molecular basis of this protection, I performed RNA-sequencing on oocytes from wild-type (N2) and daf-2(e1370) mutants after 48 hours of glucose exposure.

Glucose caused distinct transcriptional responses in each genotype, suppressing 30 transcripts in wild-type and 34 different genes in daf-2(e1370) oocytes, prior to any morphological deterioration. I identified 14 transcripts that form a candidate protective signature. These genes were downregulated by glucose in wild-type oocytes, yet under the same glucose condition, they were expressed at significantly higher levels in daf-2(e1370) oocytes compared to wild-type oocytes. The most dramatic change was in icmt-1, a regulator of cell survival signaling, which was suppressed 10-fold in response to glucose in oocytes of wild-type hermaphrodites but maintained at high levels in the oocytes of daf-2(e1370) mutants despite glucose exposure.

Mechanistically, glucose-suppressed genes in both genotypes were enriched for targets of intestinal transcription factors (PQM-1, CEH-60, ELT-2), suggesting glucose disrupts somatic support of the developing germline of the P1 generation. Conversely, compared to glucose-exposed daf-2(e1370) oocytes, glucose-exposed wild-type oocytes uniquely upregulated 1044 gene transcripts enriched for energetically costly membrane and transport functions, most likely related to a maladaptive response. These transcriptional changes predicted physiological outcomes with glucose-exposed wild-type hermaphrodites showing severely reduced late-life fertility (30.98% vs. 53.87% in controls), while daf-2(e1370) mutants maintained high reproductive success regardless of glucose enrichment.

My findings demonstrate that glucose may impair oocyte quality through the suppression of critical stress defense genes. Resilience in daf-2(e1370) mutants is likely conferred by the sustained expression of this protective program, which is sufficient to maintain oocyte quality and reproductive function with age.