News | Harvard Researchers Develop Fully Human Ovarian Organoids to Advance Treatment of Ovarian Disorders
Breakthrough: Scientists create the first fully human ovarian organoid, advancing research on female reproductive health
Harvard University’s Wyss Institute for Biologically Inspired Engineering, in collaboration with Harvard Medical School (HMS), Duke University, and biotechnology company Gameto, announced the creation of the first fully human ovarian organoid, or ovaroid. This living model can support egg-cell maturation and follicle development and can secrete sex hormones, providing a new platform for research on female reproductive health. The findings were published in eLife and provide a scientific basis for developing new treatments, particularly for infertility, ovarian cancer, and other disorders of the female reproductive system.
Successful Creation of a Fully Human Ovarian Organoid
Although every person’s life begins with an egg cell in the mother’s ovary, the human ovary has long been understudied. Most existing ovarian research uses hybrid models containing human and mouse cells. These models have limitations in replicating human ovarian function and take a long time to grow. To address this, the research team used a new method to generate complete human ovarian organoids from induced pluripotent stem cells (iPSCs), incorporating two essential cell types: oocytes and supporting cells. This innovation opens new avenues for understanding female reproductive biology and exploring potential treatments for infertility, ovarian cancer, and other conditions.
Reproducing the Biological Functions of the Ovary
“Our new method for producing fully human ovarian organoids is several times faster than existing human-mouse hybrid models and reproduces many key biological functions of the ovary. This is an important breakthrough for laboratory research on female reproductive health,” said co-first author Merrick Pierson Smela, a doctoral student at the Wyss Institute and Harvard Medical School.
The team focused on granulosa cells, ovarian support cells that help unfertilized egg cells develop within follicles and secrete estrogen and progesterone. By screening transcription factors (TFs), the team successfully induced human iPSCs to differentiate into functional granulosa cells. They generated cells with functions similar to natural granulosa cells and co-cultured them with human primordial germ cell-like cells (hPGCLCs) to create ovarian organoids.
Improving Research Efficiency and Advancing Follicle and Egg-Cell Development Studies
Using the new technology, the team cultured human ovarian organoids that produced DAZL protein, an early marker of oocyte maturation, in just four days. Ovarian organoids using mouse support cells required 32 days to show the same marker. Although the oocytes in the human organoids did not develop into mature egg cells, the team observed follicle-like structures within 16 days. Over 70 days, these developed into multilayered mature follicles capable of supporting egg-cell development.
Dr. George Church, professor of genetics at the Wyss Institute and senior author of the study, said: “Producing fully human ovarian organoids in just five days and successfully reproducing ovarian hormone signaling, oocyte maturation, and follicle development is a remarkable achievement. This will significantly accelerate important discoveries in female reproductive health.”
Future Outlook: Advancing Treatment of Ovarian Disorders and Infertility Research
The team plans to refine the ovarian organoid model by integrating additional ovarian cell types, including hormone-secreting granulosa cells, to reproduce the ovary’s complex functions more accurately. They also hope to improve the culture system so that oocytes can develop fully into mature egg cells, potentially supporting new infertility treatments.
“Women make up half the population, yet women’s health receives far less research attention and funding than conditions affecting men. I am very pleased to see this major step forward in studying the human ovary, and I hope this model will provide further insight into female reproductive health and related diseases,” said Dr. Don Ingber, founding director of the Wyss Institute, professor of vascular biology at Harvard Medical School, and professor at Boston Children’s Hospital.
News | Harvard Researchers Develop Fully Human Ovarian Organoids to Advance Treatment of Ovarian Disorders
News | Harvard Researchers Develop Fully Human Ovarian Organoids to Advance Treatment of Ovarian Disorders
Breakthrough: Scientists create the first fully human ovarian organoid, advancing research on female reproductive health
Harvard University’s Wyss Institute for Biologically Inspired Engineering, in collaboration with Harvard Medical School (HMS), Duke University, and biotechnology company Gameto, announced the creation of the first fully human ovarian organoid, or ovaroid. This living model can support egg-cell maturation and follicle development and can secrete sex hormones, providing a new platform for research on female reproductive health. The findings were published in eLife and provide a scientific basis for developing new treatments, particularly for infertility, ovarian cancer, and other disorders of the female reproductive system.
Successful Creation of a Fully Human Ovarian Organoid
Although every person’s life begins with an egg cell in the mother’s ovary, the human ovary has long been understudied. Most existing ovarian research uses hybrid models containing human and mouse cells. These models have limitations in replicating human ovarian function and take a long time to grow. To address this, the research team used a new method to generate complete human ovarian organoids from induced pluripotent stem cells (iPSCs), incorporating two essential cell types: oocytes and supporting cells. This innovation opens new avenues for understanding female reproductive biology and exploring potential treatments for infertility, ovarian cancer, and other conditions.
Reproducing the Biological Functions of the Ovary
“Our new method for producing fully human ovarian organoids is several times faster than existing human-mouse hybrid models and reproduces many key biological functions of the ovary. This is an important breakthrough for laboratory research on female reproductive health,” said co-first author Merrick Pierson Smela, a doctoral student at the Wyss Institute and Harvard Medical School.
The team focused on granulosa cells, ovarian support cells that help unfertilized egg cells develop within follicles and secrete estrogen and progesterone. By screening transcription factors (TFs), the team successfully induced human iPSCs to differentiate into functional granulosa cells. They generated cells with functions similar to natural granulosa cells and co-cultured them with human primordial germ cell-like cells (hPGCLCs) to create ovarian organoids.
Improving Research Efficiency and Advancing Follicle and Egg-Cell Development Studies
Using the new technology, the team cultured human ovarian organoids that produced DAZL protein, an early marker of oocyte maturation, in just four days. Ovarian organoids using mouse support cells required 32 days to show the same marker. Although the oocytes in the human organoids did not develop into mature egg cells, the team observed follicle-like structures within 16 days. Over 70 days, these developed into multilayered mature follicles capable of supporting egg-cell development.
Dr. George Church, professor of genetics at the Wyss Institute and senior author of the study, said: “Producing fully human ovarian organoids in just five days and successfully reproducing ovarian hormone signaling, oocyte maturation, and follicle development is a remarkable achievement. This will significantly accelerate important discoveries in female reproductive health.”
Future Outlook: Advancing Treatment of Ovarian Disorders and Infertility Research
The team plans to refine the ovarian organoid model by integrating additional ovarian cell types, including hormone-secreting granulosa cells, to reproduce the ovary’s complex functions more accurately. They also hope to improve the culture system so that oocytes can develop fully into mature egg cells, potentially supporting new infertility treatments.
“Women make up half the population, yet women’s health receives far less research attention and funding than conditions affecting men. I am very pleased to see this major step forward in studying the human ovary, and I hope this model will provide further insight into female reproductive health and related diseases,” said Dr. Don Ingber, founding director of the Wyss Institute, professor of vascular biology at Harvard Medical School, and professor at Boston Children’s Hospital.
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