Bertis Presents Research Findings on Candidate Protein Biomarkers for Precision Diagnosis of Ovarian Aging at International Conference

- At the 3rd Reproductive Aging Conference held in Cancun, Mexico from May 1st to 4th, Bertis unveiled research findings on protein biomarkers involved in ovarian aging.

- The biomarkers expected to be valuable for evaluating ovarian aging, directly associated with the health span of postmenopausal women.

On May 9th, Bertis, a company specializing in the development of proteomics-based precision medicine technology (led by CEOs Dong-young Noh and Seung-man Han), announced that it has unveiled research results identifying protein biomarker candidates involved in ovarian aging at the 3rd Reproductive Aging Conference held in Cancun, Mexico from May 1st to 4th.

Ovaries are one of the organs that age most rapidly in the body. As individuals age, the number of oocytes, the immature precursors to eggs, decreases continuously, and their quality deteriorates. This is a significant factor contributing to infertility problems in modern societies where advanced maternal age pregnancy is common. Moreover, ovarian aging is thought to be directly proportional to postmenopausal health span. Hence, accurate monitoring and prediction of ovarian aging is paramount to personalized fertility.

Bertis research team in this study presented 12 protein candidate biomarkers derived from genes specifically expressed in oocytes, which decrease in expression with increasing age in the ovaries. Additionally, they identified two proteins of them showing significant differences in expression levels between women in their 20s and 30s, suggesting these proteins as useful biomarker candidates not only for evaluating oocyte numbers but also for assessing their quality.

The ‘Reproductive Aging Conference,’ in which Bertis participated, is an international conference that focuses on the significant impact of reproductive organ tissue aging on human aging, sharing related research trends and achievements. At this conference, Bertis presented research findings on the topic of ‘Systematic Mining of Potential Biomarkers for Ovarian Reserve Using Multi-omics data sets’ through a poster presentation.

Dr. Sunghyun Huh, Head of the Bioinformatics Team at Bertis Biomarker Research Institute, who led the study, remarked, "If we can precisely diagnose the degree of ovarian aging in women, it will not only enable more effective management of infertility but also lead to personalized approaches to women's health in the future." He added, "We will continue to pursue research necessary to apply Bertis' advanced proteomics technology to aging studies, aiming to introduce technologies that can be utilized in clinical settings."

Currently, some ovarian reserve tests have been introduced, such as measurement of plasma AMH (Anti-Mullerian Hormone) or ultrasound imaging of AFC (Antral Follicle Count). neither of these tests directly represents the quantity of oocytes, and assessing the quality of oocytes, which is closely related to age, is also challenging. The research team attempted a systematic approach to identify potential biomarkers for ovarian reserve by integrating public datasets including transcriptomics and proteomics of ovarian tissues, cells, and biofluids, aiming to directly confirm the quantity and quality of oocytes.



<Image: Expression Patterns of Biomarkers of Oocyte Quantity and Quality>

To identify biomarkers for assessing the number of oocytes, the research team first selected 4,227 genes from a total of 17,769 genes in the GTEx dataset, showing decreased expression in the ovaries with increasing age. Among these, they narrowed down to 33 genes specifically expressed in the ovaries compared to other tissues. Finally, they confirmed 12 protein candidate biomarkers derived from 12 genes specifically expressed in oocytes as the final candidates.

Furthermore, to determine if the candidate biomarkers could also assess the quality of oocytes, they conducted single cell RNAseq analysis to compare the expression levels of candidate biomarkers in oocytes from average women in their 20s and 30s. As a result, two protein biomarkers among the candidates showed significant differences in expression levels between women in their 20s and 30s, suggesting their utility not only in evaluating oocyte numbers but also in assessing their quality.

Moreover, in terms of detectability of the protein biomarkers, six out of the 12 candidate protein biomarkers including two biomarkers indicating the quality of oocytes, were found in public blood protein datasets and in in-house serum spectral library. It means subset of candidates show detectability in the blood proteome. Therefore, in subsequent studies, the research team plans to confirm the expression levels of these candidate biomarkers during blood protein analysis to determine whether they can be used as indicators of ovarian aging.

Amidst worldwide anti-aging research and product development efforts, Bertis is conducting aging research using a proteomics-based approach. Leveraging its unparalleled protein profiling capabilities and a library of protein quantification analysis built over a decade of research, Bertis continues its efforts to discover markers useful for diagnosing diseases resulting from aging and developing treatments.