Probing the Development of Eggs and Sperm to Understand Infertility 

Regardless of whether you have biological children, you were preparing for the possibility before you were born. By the time you were a 1-month-old embryo, no larger than a lentil, your biology had set aside a tiny cluster of cells called primordial germ cells – the earliest precursors of eggs and sperm. 

And they are truly remarkable. Like all cells in the body, primordial germ cells contain one-half of the instructions that help make your future kids who they are: the color of their eyes, the shape of their chin, the condition of their health. But so much else rides on this little ball of cells; how they develop and respond to their environment in the womb may even determine whether they become eggs or sperm at all, or whether a fertilized egg will grow into a viable embryo. 

Yet despite the fundamental role that primordial germ cells play in human reproductive health and fertility, very little is known about them. Diana Laird, PhD, an associate professor in the UCSF Department of Obstetrics, Gynecology, and Reproductive Sciences, is one of only a handful of scientists in the world who are working to understand these cells. She suspects that their early growth and movement within an embryo may predict reproductive complications later in life, including birth defects and infertility. 

In decoding this biological mystery, Laird hopes to help explain why a woman’s eggs decline in number and quality as she ages, why a father’s age correlates with his children’s risk for neurodevelopmental disorders like autism, and how science might solve these problems. Her work could even inspire clinical techniques for artificially growing egg cells from a woman’s skin cells in the laboratory. Such technology could allow women who are unable to produce viable eggs – due to cancer, for example, or conditions like premature ovarian failure – to still have biological children. 

“That is the holy grail of reproductive biology: being able to grow a human egg in a dish,” Laird says. 

Laird chose this trailblazing path thanks in part to UCSF’s Sandler Program for Breakthrough Biomedical Research (PBBR). Founded in 1998, PBBR funds high-risk, high-reward research that is unlikely to qualify for grants from increasingly conservative funding sources such as the National Institutes of Health (NIH). 

“PBBR dares our scientists to dig deeper, ask tougher questions, and invent novel ideas and approaches that defy the status quo,” says Joe DeRisi, PhD, director of PBBR, professor in the UCSF Department of Biochemistry and Biophysics, and co-president of the Chan Zuckerberg Biohub. “You support a bold idea that nobody else will support, and if it works, it generates more grants and more science.” 

Laird’s research is a case in point. PBBR helped her launch a lab at UCSF in 2008 and later enabled her to develop the tools and early data she needed to win prestigious grants from the NIH and other organizations. A 2018 grant from the W.M. Keck Foundation, awarded Laird and UCSF colleagues Andrew Brack, PhD, and Saul Villeda, PhD, $1 million to develop a new – and unusual – animal model for investigating the link between aging and reproductive life span: a laboratory mouse with the ovaries of a naked mole rat. That study is scheduled to run through the end of 2022. 

Naked mole rat? Talk about defying the status quo. These burrowing, hairless rodents live nine times as long as lab mice, and females reproduce for up to 30 times as long. “We think the naked mole rat ovary has something to teach us; it may hold secrets that are useful for humans,” Laird says. 

That’s the goal of PBBR in a nutshell: Give young scientists the freedom to eavesdrop on nature where no one else is listening. More often than not, what they hear becomes new knowledge, which becomes new innovations, which changes lives.