Merrick Pierson Smela, a reproductive biologist and the study’s lead author, has pushed the boundaries of reproductive biology. That all changed last year with Dr. Cormier’s groundbreaking study appearing in Science Advances, where he successfully triggered meiosis from human induced pluripotent stem cells (iPSCs). Development of this cutting-edge research could lead to breakthroughs in infertility treatment and male contraceptives. Smela’s discoveries are based on her work with George Church’s team. This extraordinary collaboration demonstrates how critical interdisciplinary research is to paving the way for many promising biological and biomedical applications.
The initial goal of the study was to identify the regulatory components that initiate the onset of meiosis. This complex process is necessary for the development of eggs and sperm. By testing combinations of factors in 646,493 individual cells, Smela and his colleagues discovered three critical regulatory genes: BOLL, MEIOC, and HOXB5. Together, these findings bring a greater appreciation of the diverse genetic mechanisms that underlie gametogenesis.
Advancements in Stem Cell Technology
Merrick Pierson Smela was the first to publish a reproducible method for generating ovarian granulosa-like cells from iPSCs earlier this year. This previous work provided an incredibly strong methodological foundation for our current study. Our ultimate goal is to recreate the intricate biological dance of meiosis that is essential for crafting healthy eggs and sperm.
In their newest work, Smela’s lab injected a cocktail of genes into iPSCs to trigger meiosis-specific gene expression programs. The researchers further used small molecules that change how signals are processed inside the cells to trigger meiosis successfully.
“To create egg and sperm cells themselves, we need to be able to drive cells all the way through the meiotic cell divisions,” – Merrick Pierson Smela
The team took an innovative approach by using a synthetic mimic of vitamin A. They added a DNA methylation inhibitor, which significantly improved the efficiency of cells entering meiosis. These methodologies have provided important advances to our understanding of the basic biology of stem cell differentiation and provided concrete applications in the field of reproductive medicine.
Implications for Infertility and Contraception
The implications of this research are profound. This trend comes as the fertility rate in the United States has already fallen to historic lows, with more couples facing fertility challenges than ever before. Luckily, Smela’s innovations provide promise by addressing and creating solutions for many root causes of infertility.
Donald Ingber, considered one of the fathers of biomedical engineering, saluted the significance of this effort. He continued, “With the fertility rate in the US at a 40-year low and increasing numbers of couples and individuals experiencing infertility, the progress made by George Church’s group opens up new avenues for researchers to address these root causes.”
Smela noted how promising new infertility treatments could be developed. She further noted that the new protocol paves the way for the creation of male contraceptives in coming years. The potential to control meiosis would pave the way for groundbreaking contraceptive techniques to provide greater family planning choice and flexibility.
“I am excited about the potential of this technology to solve infertility by growing healthy eggs and sperm for people who need them,” – Merrick Pierson Smela
Simplifying the Meiotic Process
One of the most impressive aspects of Smela’s study is how it completely circumvents the primordial germ cell (PGC) state. This new advance makes it much easier to start meiosis. This development would enable more reproducible, rapid, and efficient approaches to generate gametes in vitro.
George Church, a renowned geneticist involved in the research, remarked on the complexity of creating healthy eggs and sperm: “Healthy eggs and sperm are the product of an extremely complex and error-prone process. Our research takes that further as it seeks to replicate one of its most hallmark characteristics in the petri dish.”
This research has potential far beyond simply allowing people to produce gametes. It has the promise to be a model to screen new drug candidates for reproductive toxicities. By unlocking the potential these stem cell technologies offer, researchers would have a stronger ability to determine the effects of harmful chemicals on reproductive health.