Denise Medeiros Selegato

Molecular Systems Biology Unit

European Molecular Biology Laboratory, Heidelberg

denise.selegato@embl.de

The field of medical research has long been criticized for its systemic neglect of women’s health, resulting in significant knowledge gaps that persist today. Historically, women have been underrepresented in clinical trials, with fewer than 30% of participants in early-phase studies being women. This exclusion, often justified by concerns about hormonal fluctuations and potential pregnancy risks, has perpetuated a “one-size-fits-all” approach to medicine that assumes male physiology as the default. Consequently, critical aspects of women’s health remain poorly understood, including the vaginal microbiome, drug metabolism, pregnancy outcomes, and diseases such as endometriosis. The vaginal microbiome, for example, plays a crucial role in reproductive health by maintaining an acidic environment dominated by Lactobacillus species. However, much remains unknown about how host and environmental factors influence their composition and how imbalances contribute to conditions like bacterial vaginosis, infertility, and pregnancy complications. Similarly, diseases unique to or more prevalent in women, such as endometriosis, are also under-researched. Here, we show three case studies on the use of targeted and untargeted metabolomics to address some of these disparities: (1) the citizen science project ISALA, that investigates the vaginal microbiome and metabolome of healthy women and the production of secondary metabolites by their microbial population, (2) the AROMA project, that tries to understand infertility by the chemical profiling of embryo supernatants during in vitro fertilization (IVF) and (3) the ENDO project that tries to find chemical biomarkers for the diagnoses of ovarian and peritoneal endometriosis in plasma. Overall, addressing these disparities is essential to advancing our understanding of women’s health and improving medical outcomes for half the population.

Keywords: women’s health, microbiome, untargeted metabolomics, IVF, endometriosis

Acknowledgements: Isala project has been done in collaboration with the group of Prof. Dr. Sarah Leber from the University of Antwerp, Belgium (https://isala.be/en/); AROMA and ENDO have been done in collaboration with Prof. Dr. med. Ariane Germeyer, Dr. med. Sabine Kess and Dr. med. Réka Kollarics from the Clinic for Gynecological Endocrinology and Fertility Disorders from Heidelberg University, Germany.

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