Cellular Atlas of Human Ovary Provides Insight on Reproductive and Endocrine Functions, Opens Door Toward Artificial Female Gonads

The reproductive and endocrine functions of the human ovary involve well-defined interactions among specialized cell populations. Despite the importance of the ovary in endocrine health and fertility, its functional attributes are largely uncharacterized.

Hormone and Egg Production Restoration

With the available information about the nature of human ovaries, surgeons implant previously frozen ovarian tissue to restore hormone and egg production temporarily. This method, however, does not work for long since only a few follicles survive through reimplantation.

Majority of the follicles, called primordial follicles, remain dormant and are found in the outer layer of the ovary called cortex. A tiny portion of these follicles is periodically activated and migrates into the ovary, to an area known as the growing pool. Only a few of these growing follicles can proceed to produce mature eggs that will be released into the fallopian tube during ovulation.

First Atlas of the Human Ovary

At the University of Michigan, experts have examined the functional units in the ovary by profiling more than 18,000 genes in 257 regions from the ovaries of two premenopausal donors. They also generated single-cell RNA sequencing data for 21,198 cells from three more donors and identified four major cell types and four immune cell subtypes.

To track all of the gene activity in the samples, the researchers utilized a novel technology called spatial transcriptomics. Meanwhile, strands of RNA are read to reveal the genes where they were taken. The details of the study are discussed in the paper "Cellular atlas of the human ovary using morphologically guided spatial transcriptomics and single-cell sequencing."

Their finding led to the development of the new atlas of the human ovary. It reveals the factors which allow a follicle to mature, as most follicles wither away without releasing hormones or an egg. The research team used new tools to identify the genes being expressed at a single-cell level within a tissue. Through this method, they were enabled to home in on ovarian follicles that carry the immature precursors of eggs called oocytes.

Knowing which genes are expressed in the oocytes, the scientists can test whether manipulating the genes can result in the creation of a functional follicle. This can be useful in creating an artificial human ovary which can be transplanted back into the body.

The new atlas provides information which can lead to treatments for restoring ovarian hormone production as well as the ability to produce biologically related children. The artificial ovaries can be created in the laboratories using tissues stored and frozen before being exposed to toxic medical treatments.

By guiding follicle development and tuning the ovarian environment, the engineered ovarian tissue can function for much longer than unmodified implanted tissue. This means that women can have a longer fertility window and longer period where their bodies create hormones for regulating the menstrual cycle.

Most of the ovarian follicles are already present at birth, but they never enter the growing pool and just self-destruct. The new data provided by the researchers enables the scientists to understand the factors that make a good egg. This can be useful in determining which follicle will grow, ovulate, and be fertilized to become a baby.