Advancing Infertility Treatment through Human Germ Cell Formation

Infertility affects about one in six people of reproductive age, yet its causes often remain unexplained. In some cases, infertility may originate before a person is even born, very early in their own embryonic development, when primordial germ cells—the cells that eventually give rise to eggs and sperm—first form.

Today, the California Institute for Regenerative Medicine awarded Caltech's Magdalena Zernicka-Goetz and collaborators a $2.4 million grant for work to understand the surrounding tissues and signals that guide germ cells as they emerge. The project is a collaboration with Amander Clark, founding director of the UCLA Center for Reproductive Science, Health and Education. Zernicka-Goetz is a Bren Professor of Biology and Biological Engineering and an affiliated faculty member with the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech.

"One of the great mysteries in biology is why some people experience infertility when there is no obvious explanation," Zernicka-Goetz says. "We want to go back to the very beginning, to the moment when primordial germ cells first emerge in the embryo, and understand how the surrounding tissues instruct these cells to become the precursors of eggs and sperm. Our stem cell-derived embryo models now give us a remarkable opportunity to study this previously inaccessible stage of human development."

Using two complementary stem cell-derived models of early human development, the teams will map where and when primordial germ cells arise, identify the neighboring tissues that guide them, and determine which molecular signals are essential for their development.

By creating a more detailed blueprint of this process, the researchers hope to uncover early mechanisms that contribute to infertility and to help scientists more accurately recreate human germ cell development in the lab, laying a foundation for future approaches to diagnosis and treatment.

In breakthough work in 2023, Zernicka-Goetz's team developed the first integrated human stem cell-derived embryo model from pluripotent human stem cells shown to generate primordial germ cells—the precursors of eggs and sperm.