New ovarian atlas paves the way to extended fertility and hormonal recovery

A new 'atlas' of human ovaries provides insights that could lead to treatments that restore the ability to have children, biologically linked to the production of ovarian hormones, say University of Michigan engineers. .

This deeper understanding of the ovaries means researchers may be able to create artificial ovaries in the lab using tissue that is preserved and frozen before being exposed to toxic medical treatments such as chemotherapy or radiation. means. Surgeons can now transplant previously frozen ovarian tissue to temporarily restore hormone and egg production. But this doesn't work for long, researchers say, because so few follicles (hormone-producing and egg-carrying structures) survive reimplantation.

Most follicles die without releasing hormones or eggs, so the new atlas reveals the factors that allow follicles to mature. Using new tools that can determine what genes are expressed at the single-cell level in tissues, the researchers were able to pinpoint the follicles that carry the immature precursors of eggs, known as oocytes.

“Now that we know which genes are expressed in oocytes, we can test whether influencing these genes can create functional follicles that can eventually be implanted into the body. It can be used to create artificial ovaries,” Ariela said.Shikanov, UM associate professor of biomedical engineering and corresponding author of the new study Science progresses.

The majority of follicles, called primordial follicles, remain dormant and are located in the outer layer of the ovary, called the cortex. A small portion of these follicles become activated periodically and migrate to an area of ​​the ovary known as the growth pool. Only a small number of the growing follicles produce mature eggs, which are released into the fallopian tubes.

Because of their ability to induce follicle development and regulate the ovarian environment, the researchers believe that the engineered ovarian tissue may function much longer than unmodified transplanted tissue. This means that patients have a longer fertile window and their bodies have more time to produce hormones that regulate menstrual cycles and support muscular, skeletal, sexual and cardiovascular health.

We are not talking about the use of surrogate mothers or artificial insemination. The magic we're working on is being able to coax immature cells into maturation, but we're blind if we don't know which molecules are driving that process. ”

Jun Z. Li, vice chair of the UM Department of Computational Medicine and Bioinformatics and co-corresponding author of this study

The UM team used a relatively new technique called spatial transcriptomics to track all gene activity within a tissue sample and where it occurs. They do this by reading the RNA strands, which are like notes taken from the DNA strands, revealing which genes are being read. UM researchers worked with an organ procurement organization to perform RNA sequencing of ovaries taken from five human donors.

“This is the first time that we have been able to target the follicles and oocytes for transcriptional analysis, allowing us to see which genes are active,” Shikanov said.

“The majority of ovarian follicles are already present at birth, never enter the growth pool, and eventually self-destruct. This new data allows us to understand what makes a good egg and which follicles We can start to understand more about what determines whether a baby will grow, ovulate, fertilize, and develop into a baby.”

UM's research is part of the Human Cell Atlas project, which aims to “discover all the different cells, their molecular characteristics, and where they are located in order to understand how the human body works and what's wrong with disease. The purpose is to create a map.

Shikanov, Lee, and their UM collaborators, including Sue Hammoud, associate professor of human genetics and urology, have mapped other parts of the female reproductive system, including the uterus, fallopian tubes, and ovaries. There is. Other contributors include girlfriend Andrea Suzanne Kuliahsa Jones, formerly of UM and now at Duke University, and D. Ford Hannum, a UM graduate student and research assistant in bioinformatics.

This research was partially funded by the Chan Zuckerberg Initiative. Additional financial support was provided by the National Institutes of Health.