News | Human Ovary Atlas Offers New Hope for Extending the Fertile Lifespan
A new human ovary "atlas" created through research by University of Michigan engineers offers new hope for restoring ovarian hormone production and fertility. This detailed study raises the possibility of creating artificial ovaries in the laboratory using tissue stored and frozen before exposure to toxic treatments such as chemotherapy and radiation. Surgeons can currently transplant previously frozen ovarian tissue to temporarily restore hormone and egg production. Researchers say, however, that the effect does not last because few follicles survive reimplantation.
The new ovarian atlas reveals factors that help follicles mature, as most follicles shrink without releasing hormones or eggs. Using new tools, the team identified genes expressed at the individual-cell level within tissue, enabling detailed study of follicles containing immature eggs.
"Now that we know which genes are expressed in the eggs, we can test whether influencing those genes can create functional follicles. This could be used to create an artificial ovary that could eventually be transplanted back into the body," said Ariella Shikanov, associate professor of biomedical engineering at the University of Michigan.
Most follicles, called primordial follicles, are dormant in the ovarian cortex, the ovary's outer layer. Some periodically activate and move to an area called the growing pool. Only a few growing follicles produce mature eggs and release them into the fallopian tubes.
By guiding follicle development and adjusting the ovarian environment, the team believes engineered ovarian tissue could function longer than unmodified transplanted tissue. Patients could therefore have a longer fertile window and more time producing hormones that regulate the menstrual cycle and support muscle, bone, sexual, and cardiovascular health.
"We are not talking about using a surrogate or artificial insemination. Our goal is to trigger immature cells to mature, but without knowing which molecules drive the process, we are working blindly," said Jun Z. Li, associate chair of computational medicine and bioinformatics at the University of Michigan.
The University of Michigan team used a relatively new technique called spatial transcriptomics to track all gene activity in tissue samples and where it occurred. They read RNA strands, which function like notes copied from DNA, to reveal which genes were being read. Working with an organ procurement organization, the researchers sequenced RNA from the ovaries of five human donors.
"This is the first time we have been able to perform transcriptomic analysis specifically on ovarian follicles and oocytes, allowing us to see which genes are active," Shikanov said.
"Most ovarian follicles present at birth never enter the growing pool and eventually self-destruct. These new data are beginning to show us what makes a high-quality egg—what determines which follicle will grow, ovulate, be fertilized, and become a baby."
The University of Michigan's work is part of the Human Cell Atlas project, which aims to create "maps of all the different cells, their molecular characteristics, and where they are located, to understand how the human body works and what goes wrong in disease."
The study was funded in part by the Chan Zuckerberg Initiative, with additional support from the National Institutes of Health.
News | Human Ovary Atlas Offers New Hope for Extending the Fertile Lifespan
News | Human Ovary Atlas Offers New Hope for Extending the Fertile Lifespan
A new human ovary "atlas" created through research by University of Michigan engineers offers new hope for restoring ovarian hormone production and fertility. This detailed study raises the possibility of creating artificial ovaries in the laboratory using tissue stored and frozen before exposure to toxic treatments such as chemotherapy and radiation. Surgeons can currently transplant previously frozen ovarian tissue to temporarily restore hormone and egg production. Researchers say, however, that the effect does not last because few follicles survive reimplantation.
The new ovarian atlas reveals factors that help follicles mature, as most follicles shrink without releasing hormones or eggs. Using new tools, the team identified genes expressed at the individual-cell level within tissue, enabling detailed study of follicles containing immature eggs.
"Now that we know which genes are expressed in the eggs, we can test whether influencing those genes can create functional follicles. This could be used to create an artificial ovary that could eventually be transplanted back into the body," said Ariella Shikanov, associate professor of biomedical engineering at the University of Michigan.
Most follicles, called primordial follicles, are dormant in the ovarian cortex, the ovary's outer layer. Some periodically activate and move to an area called the growing pool. Only a few growing follicles produce mature eggs and release them into the fallopian tubes.
By guiding follicle development and adjusting the ovarian environment, the team believes engineered ovarian tissue could function longer than unmodified transplanted tissue. Patients could therefore have a longer fertile window and more time producing hormones that regulate the menstrual cycle and support muscle, bone, sexual, and cardiovascular health.
"We are not talking about using a surrogate or artificial insemination. Our goal is to trigger immature cells to mature, but without knowing which molecules drive the process, we are working blindly," said Jun Z. Li, associate chair of computational medicine and bioinformatics at the University of Michigan.
The University of Michigan team used a relatively new technique called spatial transcriptomics to track all gene activity in tissue samples and where it occurred. They read RNA strands, which function like notes copied from DNA, to reveal which genes were being read. Working with an organ procurement organization, the researchers sequenced RNA from the ovaries of five human donors.
"This is the first time we have been able to perform transcriptomic analysis specifically on ovarian follicles and oocytes, allowing us to see which genes are active," Shikanov said.
"Most ovarian follicles present at birth never enter the growing pool and eventually self-destruct. These new data are beginning to show us what makes a high-quality egg—what determines which follicle will grow, ovulate, be fertilized, and become a baby."
The University of Michigan's work is part of the Human Cell Atlas project, which aims to create "maps of all the different cells, their molecular characteristics, and where they are located, to understand how the human body works and what goes wrong in disease."
The study was funded in part by the Chan Zuckerberg Initiative, with additional support from the National Institutes of Health.
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