A Caltech Lab Gets $2.4 Million to Study Where Infertility May Begin

Some cases of infertility may begin before a person is born — very early in embryonic development, when the cells that will one day become eggs and sperm first appear. A Pasadena laboratory now has $2.4 million from the state to study that early moment.

The grant, from the California Institute for Regenerative Medicine, the state’s stem cell agency, funds a collaboration led by Caltech biologist Magdalena Zernicka-Goetz with Amander Clark of UCLA. According to announcements from both universities, the teams will try to map how primordial germ cells form and what surrounding tissues and signals guide them — work the researchers say could eventually help explain infertility that today has no clear cause.

The award is one of two the agency directed to scientists affiliated with UCLA’s Broad Stem Cell Research Center, part of $4.9 million announced September 24, according to a UCLA Health news release. The other grant supports research into an irreversible form of vision loss.

Zernicka-Goetz, the Bren Professor of Biology and Biological Engineering at Caltech, leads the project. Clark, the founding director of the UCLA Center for Reproductive Science, Health and Education, is a co-investigator.

Primordial germ cells are the cells that eventually give rise to eggs and sperm. They form very early, at a stage that has been hard to observe directly. Using two laboratory models built from stem cells, the teams plan to track where and when those cells appear, identify the tissues around them, and pin down the molecular signals that steer their development, the Caltech announcement said.

The researchers describe the work as laying a foundation for future approaches to diagnosis and treatment, according to Caltech. They hope a clearer picture of this early process could reveal mechanisms that contribute to infertility and help other scientists recreate germ-cell development in the lab more accurately.

Infertility affects about one in six people of reproductive age, both universities said — a figure consistent with a 2023 World Health Organization report estimating that roughly one in six adults worldwide experience infertility at some point. Many cases have no identified cause.

“One of the great mysteries in biology is why some people experience infertility when there is no obvious explanation,” Zernicka-Goetz said in the Caltech release. “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.”

Zernicka-Goetz’s laboratory has worked at this frontier before. In 2023, her team reported an integrated human embryo model, grown from stem cells, that Caltech says was the first shown to generate primordial germ cells. That announcement — made alongside competing reports from teams in Israel and the United States — drew scientific debate at the time over how closely such models resemble real embryos.

Clark, for her part, has spent years studying how germ cells arise. Her lab uses human stem cells to model their development, and she has become a frequent public voice on reproductive science.

The cells at the center of the work first appear at the very beginning of human development. The new grant is a bet that watching them form — from that beginning — is where the answers start.