Pioneering Research at UCLA Opens Doors for Infertility Treatments

In a groundbreaking study, UCLA scientists have unveiled the first detailed map of how the ovarian reserve develops in primates, potentially paving the way for innovative treatments for infertility and polycystic ovary syndrome (PCOS). This research, a result of a collaborative effort with Harvard, UC San Francisco, and the Oregon National Primate Research Center, was published in Nature Communications and reflects six years of dedicated study.

What is Ovarian Reserve?

The ovarian reserve refers to the finite supply of eggs a woman is born with, which plays a critical role not only in reproduction but also in hormonal balance throughout a woman's life. Amander Clark, the study's senior author and professor at UCLA, emphasized its importance: "It's essential for motherhood, guiding puberty, and marking the countdown to menopause. This new manual gives scientists the tools to develop more precise human ovarian models to investigate ovarian diseases effectively."

Using Primates to Illuminate Egg Development

Despite its significance, the process of ovarian reserve formation has remained largely elusive, primarily due to the challenges in studying the pre-birth development in humans. To address this, researchers turned to the rhesus macaque, a primate closely genetically related to humans, which undergoes similar ovarian development. "We needed a model with similar physiology to humans," explains Sissy Wamaitha, the lead author of the paper.

Mapping Key Development Stages

The research team successfully identified critical phases in ovarian reserve development, such as the formation of the ovaries and the creation of follicles, the protective structures around the eggs. They employed advanced techniques like single-cell sequencing and spatial transcriptomics to analyze and capture these developmental milestones at the molecular level.

Understanding Mini-Puberty

One of the most intriguing discoveries from this study is the explanation behind mini-puberty—a hormonal surge that infants experience shortly after birth. Researchers found that specialized hormone-producing cells in the ovary activate just before birth, leading to a period of 'practice growth' that contributes to this hormonal spike. For infants lacking this surge, it could indicate early signs of ovarian dysfunction, offering a potential early biomarker for issues such as PCOS, which impacts about 10% of women globally.

Towards Advanced Ovarian Models

The insights gained from this atlas have significant implications for stem cell research, enabling the creation of more accurate ovarian organoids in the lab. Previously, the absence of detailed knowledge hindered scientists' ability to generate the correct cell types necessary for ovarian development. With the newfound understanding, researchers are now working to engineer critical ovarian support cells from induced pluripotent stem cells.

A Future of Improved Women's Health

If successful, this initiative could lead to the combination of engineered support cells with lab-grown germ cells, fostering the creation of complex 3D ovarian models. Clark notes, "This project highlights the profound impact of fundamental research, advancing our knowledge of an often-overlooked organ to develop tools that could significantly enhance women's and girls' health worldwide."