This year started dramatically for me. After more than a decade of research on mitochondrial disorders, I stepped into the field of sex differences. And I couldn\u2019t be luckier. This year, the very first European conference on sex differences was held in Heidelberg at the EMBL Advanced Training Centre from 27 to 30 April 2026.<\/p>\n\n\n\n
The symposium brought together a global community of researchers to address a long-understudied frontier of biology. While sexual dimorphism is often observed in clinical outcomes and physiological traits, the precise molecular mechanisms driving these differences frequently remain elusive. I have experienced many times that researchers do care about sex as a variable. They can precisely describe certain phenomena in males and females, but this meeting focused on moving beyond mere description to explore the exact mechanisms. These may be genetic, hormonal, or environmental, and together they lead to sex-specific health outcomes. I found it special that more than 100 participants on site (plus even more virtually) were interested in sharing their findings with colleagues to reach the goal.<\/p>\n\n\n\n <\/p>\n\n\n\n As I said, I am new in the field, but luckily, the symposium opened with a keynote lecture by Arthur Arnold, University of California, Los Angeles, USA. He provided a historical perspective on how scientific opinions regarding sex differences have evolved over the decades, while highlighting the significant challenges that remain in the field \u2013 like detangling the role of sex hormones from the role of sex chromosomes or sex-specific gene expression regulation by \u201cdosage compensators\u201d.<\/p>\n\n\n\n A recurring theme on the first day was the complexity of sex chromosome biology. Agnese Loda, Institute Imagine\/Institut Pasteur, France, and Anna Naumova, McGill University, Canada, discussed the silencing of the X chromosome by Xist (RNA covering the X chromosome to \u201csilence\u201d it and hence regulating the X chromosome expression dosage in females) and the critical role of reversible and irreversible epigenetic changes in sex differentiation, which in fact fluctuate in females. They demonstrated that the “male factor” is only one part of the equation, as the expression and regulation of sex chromosomes themselves (including the X chromosome, of course!) are fundamental.<\/p>\n\n\n\n The complex tasks need to be solved from multiple perspectives. Hence, the diversity of research models is amazing. Margarida Cardoso-Moreira, The Francis Crick Institute, UK, uses fish (Poeciliidae) as a model to study placentation and sex differences, whereas Bruno Hurdy, Universit\u00e9 C\u00f4te d’Azur, Institute of Biology Valrose \u2013 iBV, France, demonstrated that somatic cells carrying XX or XY sex chromosomes in neurons can influence the phenotype of other cells in the midgut of Drosophila. Interestingly, specific regions of the midgut show morphological differences between males and females and shape the susceptibility to cancer.<\/p>\n\n\n\n Day two transitioned into the systemic impacts of sex on immune cells, cancer, and ageing. Yasmine Belkaid, Institute Pasteur, France, presented her research on how maternal immunity controls lactogenesis and the accumulation of T-cells during pregnancy and lactation. Another interesting finding is that the immunological memory arising from immune system\u2013microbiota interactions, which is acquired during pregnancy, lasts a lifetime.<\/p>\n\n\n\n Elizabeth Rideout, University of British Columbia, Canada, noted that protein synthesis levels are notably higher in female Drosophila and highlighted the role of mitochondrial biogenesis in protein synthesis and its adaptation in females, who either produce oocytes or nurture offspring during evolution.<\/p>\n\n\n\n Alexandra Milona, The Francis Crick Institute, UK, presented striking findings on the mouse intestine, which expands during pregnancy and lactation but does not return to its original size afterwards. We can see the changes morphologically and on a molecular basis, but research about microbial changes in the intestine is a challenge for the future. Besides more \u201cclassical\u201d models \u2013 males vs. females \u2013, scientists also use trickier species in which sex determination is polygenic (like Danio rerio) or non-standard from the human point of view. Meital Oren-Suissa, Weizmann Institute of Science, Israel, explored sexual diversity in synaptic remodelling and dopaminergic neuronal vulnerability in C. elegans, specifically discussing the aspects of sex differences in males. C. elegans is a species that can function either as a male or as a hermaphrodite. But Oren-Suissa extended this work to mammalian systems.<\/p>\n\n\n\n When discussing sex differences, we must distinguish whether it refers to biological sex, which can be either chromosomal or gonadal. James Cleland, German Cancer Research Centre (DKFZ)\/EMBL Heidelberg, Germany, talked about lipid metabolism in hepatocytes in Four Core Genotype rats, one of the most extensively studied models. These animals carry the SRY gene on an autosome, which allows researchers to dissect the effect of sex chromosomes from the effect of gonads (sex hormones) and identify key players in the metabolism by integrating expression and metabolic data, in Cleland\u2019s work, even with zonation-associated variation between hepatocytes.<\/p>\n\n\n\n The third day focused more on disease pathology and the tools required to study it. Jean-Charles Gu\u00e9ry, Toulouse INSERM, France, discussed the microbiological aspects of sex differences with a specific focus on autoimmunity and Systemic Lupus Erythematosus (SLE) and X-chromosome inactivation (XCI), which was a hot topic discussed in multiple talks. Sarah Hoelzl, The Technical University of Munich, Germany, showed that certain genes \u201cescape\u201d XCI across multiple tissues and that distal parts of the X chromosome lose Xist during the ageing process. Taru Tukiainen, Institute for Molecular Medicine, Finland, presented that large-scale datasets, such as GWAS (Genome-Wide Association Studies) from hundreds of thousands of Finnish samples, are excellent for determining the necessity of XCI regulation without always requiring specialised models. She illustrated how sex chromosomes, together with endocrine context and sex-specific life-history exposures, shape the disease risk and hence observed sex differences in health and disease in humans.<\/p>\n\n\n\n In recent years, the scientific community has faced controversy regarding the use of artificial intelligence (AI) in research, particularly within the publication process. However, in my humble opinion, at the conference, the topic was discussed in a very wise way to save time and resources – for example, by using the IDentif.AI tool in the laboratory of Brian Aguado, University of California, San Diego, USA. Aguado presented not only research on the influence of the extracellular matrix and the use of hydrogels as tools to determine sex-specific mechanisms of cardiovascular disease progression but also how AI can be used to streamline research in determining ideal experimental conditions.<\/p>\n\n\n\n Kristina Haase, EMBL Barcelona, Spain, presented amazing and innovative bioengineering techniques for modelling the novel 3D vascularized in vitro tissues for disease modelling, e.g. placenta (which has its own sex, of course!), cardiac inflammation, and breast cancer. These models utilise dextran matrices and minimise the need for animal sacrifice. <\/p>\n\n\n\n The difference between sexes doesn\u2019t lie solely in the sex hormones or sex chromosomes themselves, i.e. the DNA sequence, but obviously, as Claudia Keller Valsecchi, University of Basel, Switzerland, showed us in the detailed reversible and irreversible neuronal epigenetic modifications. In her work, she presented how Xist recruits during XCI various protein complexes to the X chromosome that drive multilayered chromatin remodelling.<\/p>\n\n\n\n Xiaohong Xu, Fudan University, China, used mice to study behavioural circuits, particularly in relation to mating and aggression, another aspect, besides sex differences, present in metabolic processes and morphological features. This work clarifies that the differences in the neural mechanisms govern sexually dimorphic behaviours in males and females. Some of these differences may be genetic, while others may be a response to hormonal status, for example, male mice exposed to estrogen during development.<\/p>\n\n\n\n The final day of the symposium emphasised the Y chromosome and its translation to clinical application. James Turner, The Francis Crick Institute, UK, delivered an impactful talk on the Y chromosome, demonstrating that its role extends far beyond the SRY gene \u2013 it is essential for embryogenesis and contains genes that influence the fate of every somatic male cell. Osvaldo Contreras, Victor Chang Cardiac Research Institute, Australia, utilised a zebrafish model to study how sex determines the size and morphology of the heart. And finally, to emphasise the clinical application, we learned that chemotherapy timing could be adjusted according to the menstrual cycle in breast cancer patients to maximise survival rates, in the talk by Colinda Scheele, KU Leuven University, Belgium.<\/p>\n\n\n\n Beyond about forty talks, the symposium brought together a vibrant scientific community. The event also featured over sixty posters. Innovative use of online platforms like Slido encouraged high engagement, and I do appreciate the ‘Poster sneak peek’, which offers you the possibility to go through the posters before presenting yours. Among the posters, the best poster prize went to: Rayyan Gorashi, PhD student from the University of California, USA, Alessia Karasani, PhD student from the Technical University of Munich, Germany, and Tarek Taha from the Rambam Health Care Campus, Israel – poster presented by Ithai Waldhorn. Congratulations!<\/p>\n\n\n\n The EMBO | EMBL Symposium \u2018Sex differences in health and disease\u2019 highlighted a shift in the field, moving from ‘just’ documenting sex differences to deciphering the underlying mechanisms behind this phenomenon. By integrating bioengineering and cell biology, researchers can better understand and study how sex-specific biology influences health, ultimately leading to more effective and personalised medicine for all.<\/p>\n\n\n\n I would like to thank the organisers Edith Heard, Brian Aguado, Kristina Haase, Irene Miguel-Aliaga and EMBL Events for choosing me as an event reporter. I would also like to thank Lukas Chmatal, Institute of Physiology CAS, Czech Republic, for his support of my participation at #EESSexDifferences and in the field. Finally, I hope we all meet again in two years!<\/p>\n\n\n\n The EMBO | EMBL Symposium \u2018Sex differences in health and disease<\/a>\u2019 took place between 27 \u2013 30 April 2026 in Heidelberg, Germany, and virtually.<\/em><\/p>\n\n\n\n![\"\"](\"https:\/\/www.embl.org\/about\/info\/course-and-conference-office\/wp-content\/uploads\/HG_7BFCakAAHYgR-1024x768.jpeg\")
<\/figure>\n\n\n\nDay <\/strong>one<\/h2>\n\n\n\n
Day <\/strong>two<\/h2>\n\n\n\n
Day three<\/strong><\/h2>\n\n\n\n
Day four<\/strong><\/h2>\n\n\n\n
In conclusion<\/strong><\/h2>\n\n\n\n
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