Infertility affects 15% of couples worldwide, with female factors-mainly reduced oocyte quality and quantity-responsible for 40% of cases. Assisted reproductive technologies (ART), particularly IVF, offer solutions but are limited by the absence of reliable, non-invasive biomarkers for assessing oocyte and embryo quality. Current morphological assessments are subjective and may fail to detect molecular defects. Granulosa cells (GCs), especially cumulus (cGCs) and mural (mGCs) subtypes, which closely support oocyte development, may offer a promising source of biomarkers.
Reactive oxygen species (ROS) play dual roles in folliculogenesis and ovulation-beneficial at physiological levels but harmful in excess, leading to oxidative stress and reduced reproductive success. Despite numerous studies, the relationship between oxidative stress biomarkers and ART outcomes remains unclear, partly due to methodological variability and insufficient understanding of ROS compartmentalization.
This thesis of Nuan Lin investigates oxidative stress in GCs as a potential diagnostic tool for ART. Chapter 2 identifies a six-gene oxidative stress-related signature in GCs linked to ovarian aging. Chapter 3 applies diamond-based relaxometry to measure subcellular ROS levels in cGCs and mGCs, revealing mitochondria as the primary site of ROS generation. Chapter 4 examines FSH-induced oxidative responses, showing that supraphysiological FSH levels increase mitochondrial ROS and cause lipid peroxidation. Chapter 5 explores whether mitochondrial redox responses in cGCs correlate with oocyte and embryo quality, finding that better redox balance is associated with higher fertilization rates.
Together, these studies offer new insights into oxidative stress dynamics in GCs and highlight their potential as biomarkers to improve ART outcomes.
Nuan Lin is part of Health in Context.
