Reproductive Health/Reproductive Medicine – Kristina Gemzell Danielsson's research group

Globally, approximately 10% of couples experience infertility, and despite continuous optimization of assisted reproductive technologies (ART), pregnancy rates remain limited at 30–35% per treatment cycle.

A major focus of our work is to understand endometrial function and receptivity, which lie at the core of both infertility management and the development of novel fertility control strategies. Endometrial regeneration and receptivity are still poorly understood, largely due to ethical constraints and the lack of physiologically relevant human models. Clinical challenges such as thin endometrium and recurrent implantation failure remain inadequately addressed.

To overcome these limitations, we develop and apply advanced human in vitro platforms, including three-dimensional endometrial cultures, assembloids, and organ-on-chip systems. These models are designed to recapitulate key microenvironmental cues, multicellular interactions, and dynamic hormonal responses relevant to human endometrial regeneration and implantation. Our three-dimensional endometrial culture model, which closely mimics the in vivo human endometrium, represents a unique and powerful tool to study molecular mechanisms underlying human embryo implantation. Vascular and immune components are incorporated into microfluidic, perfused organ-on-chip platforms to model dynamic cellular interactions in a physiologically relevant environment. These systems are further used to identify and test novel endometrial contraceptive targets. Omics data are integrated using custom pipelines prioritising ligandability, cycle specificity, and tissue-specific.

Our single-cell RNA sequencing (scRNA-seq) studies have revealed unexpected stromal heterogeneity, including perivascular progenitor cell populations that appear critical for endometrial regeneration. Advanced spatial biology is in progress in understanding endimetrial fucntion.

We study developing non-invasive molecular marker panels to identify high-quality embryos with the greatest potential for successful implantation and healthy development. Our overarching goal is to improve embryo selection strategies in assisted reproductive technologies (ART) while minimizing any intervention that could compromise embryo viability.

As a first step, we demonstrated the feasibility of using embryo-derived mRNA profiles as a non-invasive tool for embryo quality assessment. The study showed promising results, supporting the concept that molecular signatures present in embryo culture media can provide meaningful biological insights into embryo competence.

Building on this work, our current research expands toward small RNA profiling, including microRNAs and other regulatory small RNAs, to further refine and strengthen non-invasive diagnostic panels. By integrating transcriptomic signals across RNA classes, we aim to develop robust, reproducible, and clinically translatable biomarkers that can support evidence-based embryo selection in IVF clinics.

Through close collaboration between basic scientists, clinicians, and embryologists, our experimental program bridges molecular biology and clinical application, with a strong emphasis on translational impact and patient safety.

(Add a figure: ROC – mRNA?)

Exosomes and other extracellular vesicles are increasingly recognised as critical mediators of intercellular communication. These vesicles carry a diverse bioactive cargo, including proteins, DNA, mRNA, and microRNAs, capable of modulating recipient cell behaviour. We investigate exosomes secreted by pre-implantation stage human embryos to elucidate their potential role in embryo–endometrial cross-talk and implantation competence.

Our research adopts a translational framework to elucidate mechanisms underlying the initiation and progression of breast, ovarian, and endometrial cancers, with a strong emphasis on prevention. We focus on the identification and validation of biomarkers for early detection and risk stratification, aiming to improve predictive models and enable timely clinical interventions.

Using spatial transcriptomics and single-cell approaches, we aim to identify early molecular alterations, cellular niches, and biomarkers that link endometriosis-associated ovarian cancer (EAOC).

We develop patient-derived organoid systems, including advanced mini-breast model, to recapitulate the architecture and microenvironment of human tissues for dissecting early oncogenic events and evaluating preventive strategies in a physiologically relevant context.

A central aspect of our work involves mechanistic studies of hormone-driven signalling pathways in cancer initiation, particularly in BRCA-associated malignancies. By integrating molecular, cellular, and functional analyses within these organoid systems, we aim to uncover actionable targets for non-invasive preventive interventions.

Our ultimate objective is to transform the mechanistic insights into clinically applicable solutions that reduce cancer incidence and improve patient outcomes.