Scientists develop mini-ovaries that could advance infertility research

Scientists have successfully created laboratory-grown human ovary models from stem cells, marking a potential breakthrough in infertility and reproductive disorder research.

The findings, presented at the Joint Congress of the European Society of Paediatric Endocrinology and the European Society of Endocrinology, offer new insights into female reproductive development.

The miniature organoids replicate key structural and functional features of ovarian follicles, which contain eggs and the cells that nurture them.

Researchers at the Institut Pasteur in Paris developed the models by differentiating human induced pluripotent stem cells into granulosa-like cells—essential for egg maturation—and primordial germ cell-like cells, then combining them to form human ovaroids.

While other ovaroid models exist, this is the first to combine these cell types without using exogenous transcription factors.

“Transcription factors are proteins that bind to specific DNA sequences and turn nearby genes on or off, so using external ones can override the innate genetic programme of the cells, which makes the derived populations unsuitable for disease modelling,” said senior author Dr Anu Bashamboo.

The models could improve understanding of differences in sex development (DSDs), conditions in which sex chromosomes and gonadal or anatomical sex do not align. Though rare (1 in 4,500 births), milder forms affect around 1 in 200 people.

During early human development, gonads begin forming at four weeks and develop into testes or ovaries by week six, making the process difficult to study.

Over the past 15 years, scientists have identified numerous genes involved in atypical gonad development, but around half of DSD cases due to gonad formation still lack a genetic diagnosis.

The same team previously generated Sertoli cells—testicular support cells commonly affected in DSDs—from human stem cells. They showed that Sertoli cells with male chromosomes (XY) and a genetic variant linked to atypical testis development could not form the 3D tubular structures of testis cords.

“By creating human-specific, lab-grown models of both testicular and ovarian development using induced pluripotent stem cells, the research overcomes key limitations in the field—particularly the lack of suitable animal models due to poor conservation of developmental genes and mechanisms across species—and provides a powerful platform for studying gene function in a controlled environment,” said Dr Bashamboo.

The new models offer a scalable system that could aid reproductive disorder research and lead to treatments for ovarian dysfunction and infertility.

“Our work more broadly contributes a scalable, human-relevant model system to developmental biology, reproductive medicine and genetic diagnostics. It bridges the gap between basic science and clinical application, offering tools that could improve diagnostic yields and support the development of targeted treatments for individuals with DSDs and related reproductive disorders, including infertility and certain types of ovarian tumours,” said Dr Bashamboo.

Dr Bashamboo added: “Our model also opens up new possibilities for screening drugs and environmental toxins affecting human gonads, personalised medicine and future therapeutic interventions.”