New Raman spectroscopy method reveals how egg cell metabolism declines with age

The quality of a woman’s egg cells, or oocytes, is one of the most important factors for fertility and successful embryo development. As women age, oocyte quality naturally declines, leading to reduced fertility, higher risks of chromosomal abnormalities, and poorer pregnancy outcomes. Until now, most methods to study these changes have relied on invasive techniques that require fixing cells or adding dyes, limiting their relevance for reproductive medicine.

A new study, published in iMetaMed (Wiley), introduces a noninvasive way to measure how egg cell metabolism changes with age. The team, led by scientists at Peking Union Medical College Hospital and the University of Glasgow, combined single-cell Raman spectroscopy with advanced computational analysis to track biochemical changes in mouse oocytes.

“Raman spectroscopy lets us capture a molecular fingerprint of living cells without labels or dyes,” said co-corresponding author Dr. Jiabao Xu of the University of Glasgow. “By applying trajectory analysis and high-resolution Raman imaging, we could follow how metabolism shifts during oocyte maturation and with age.”

The researchers studied 166 live mouse oocytes at different developmental stages and ages, along with high-resolution spatial maps of 9 additional oocytes. They discovered that while the nuclear development of older oocytes appeared normal, their metabolic maturation lagged behind. This developmental “asynchrony” was accompanied by a striking loss of cytochrome c—a molecule essential for mitochondrial energy production—in older eggs.

“These findings suggest that mitochondrial dysfunction is a central factor in the age-related decline of oocyte quality,” said Dr. Hanbi Wang, co-corresponding author at Peking Union Medical College Hospital. “It provides a biochemical explanation for why fertility declines with age.”

In addition to tracking age-dependent changes, the study mapped the precise distribution of lipids, proteins, and cytochrome c within individual oocytes. This dual strategy of live profiling and spatial imaging represents a new framework for studying reproductive aging.

The authors believe their platform could be adapted for clinical applications, such as noninvasive screening of oocyte quality in assisted reproductive technologies (ART).

“This work highlights the potential of label-free Raman spectroscopy to transform how we assess egg cell health,” said Xu. “Our approach could eventually guide fertility treatments by identifying oocytes with the highest developmental potential.”

The research was published as open access in iMetaMed on 24 September 2025.