Novel multi-omic biomarkers to combat oocyte and ovarian aging.

Abstract

Understanding oocyte and ovarian aging has become critically important, as trends in family planning evolve, with many women choosing to have children later in life. The ovary, a crucial organ in female reproduction, is particularly susceptible to age-related changes and is one of the organs that exhibit functional deterioration most distinctly with age. The aging of female reproductive systems also affects longevity and various health outcomes. A better understanding of both oocyte and ovarian aging will lay the cornerstone to elucidate the phenomenon of longevity in women. Here, clinical data from 400 women of various ages undergoing intracytoplasmic sperm injection (ICSI) have been analyzed, including Anti-Müllerian Hormone (AMH) and Follicle-Stimulating Hormone (FSH) levels, the number of recovered oocytes, blastocyst rates, pregnancy rates, and live birth rates. Our analyses revealed significant differences in the aforementioned rates between patients of young and advanced age. For the biomarker analysis, we further utilised a novel predictive performance of age-associated gene expression signatures for oocyte aging, demonstrating its potential to provide molecular-level insights into oocyte quality over time. By analyzing RNA sequencing data generated from human oocytes of different ages, a genome-wide landscape of age-associated gene expression has been described. Additionally, metabolome profiling has been performed on young and reproductively aged mice, serving as a model for human ovaries. Changes in metabolites of the murine ovaries during aging have been recorded. In conjunction with traditional biomarkers, multiomics data represent a transformative approach in reproductive health, and they may offer personalised risk assessments and interventions to mitigate age-related fertility decline in women. Our metabolome profiling provides a valuable resource for elucidating the metabolomic basis of ovarian aging. Our findings offer novel insights into systemic shifts associated with oocyte and ovarian aging. This integrated approach may unlock new avenues for fertility preservation, ovarian rejuvenation, and assisted reproduction.