Scientists have developed a new model of tiny human ovary structures, called ovaroids, using stem cells. This breakthrough was presented at the first Joint Congress of the European Society of Paediatric Endocrinology (ESPE) and the European Society of Endocrinology (ESE). The discovery may help us better understand and treat conditions where ovaries do not form or work properly. These include rare differences in sex development (DSDs) and infertility.
Early Sex Development Is Hard to Study
Sex determination in humans happens very early during embryo development. Gonads, which become either testes or ovaries, start forming around four weeks after fertilization. By six weeks, the gonads begin to specialize. However, sometimes the development does not follow typical patterns. This can lead to differences in sex development, where a person’s chromosomes and physical sex characteristics don’t match. Although these cases are rare, occurring in about 1 in 4,500 people, milder forms affect about 1 in 200 individuals.
DSDs are often noticed before birth or in infancy but can also appear during puberty or later. While scientists have identified many genes involved in gonad development over the past 15 years, about half of children with DSDs related to gonad formation still do not have a clear genetic diagnosis.
Creating Human Ovaroids From Stem Cells
Researchers at the Institut Pasteur in Paris used human induced pluripotent stem cells (hiPSCs) to create two types of ovarian cells: granulosa-like cells, which support egg growth, and primordial germ cell-like cells, which are early reproductive cells. When these two cell types were combined, they formed ovaroids—miniature organ-like structures that mimic key parts of ovarian follicles.
This is the first time scientists have created ovaroids by producing both granulosa-like and primordial germ cell-like cells together, without adding external genetic factors. These lab-grown ovaroids replicate important structural and functional features of real ovaries.
Related Advances in Testis Cell Models
Previously, the same team developed testis somatic cells called Sertoli cells from hiPSCs. Sertoli cells play a key role in testis development and are often affected in DSDs. Using male chromosome cells (XY) with a gene variant linked to atypical testis formation, the researchers found these cells could not form normal three-dimensional structures called testis cords. This resulted in a gonad model that mimics testis development disorders seen in DSDs.
A New Tool for Studying Human Gonad Development
Dr. Bashamboo, a lead researcher, explained that creating human-specific lab models for both ovarian and testis development solves major challenges in this field. Animal models often fail because the genes and developmental processes differ greatly between species. These human cell-based models allow scientists to study gene functions more accurately in a controlled environment.
This research offers a scalable and relevant system for developmental biology, reproductive medicine, and genetic diagnosis. It connects basic science with clinical needs by providing tools to improve diagnosis and create targeted treatments for people with DSDs, infertility, and certain ovarian tumors.
Future Possibilities
Dr. Bashamboo also noted that these models could be used to test drugs and environmental toxins that affect human gonads. They open doors for personalized medicine and new therapies to treat reproductive disorders in the future.
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