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Renee A. Reijo Pera, Ph.D.

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Basic Research Translates into Help for Those Facing Infertility

Dr. Renee A. Reijo Pera, Ph.D.For the past 15 years, Renee A. Reijo Pera, Ph.D., has been studying the earliest stages of human development, from the development of sperm and egg cells and through the development of the embryo.

The NICHD funds her work, in part, through the Specialized Cooperative Centers Program in Reproduction and Infertility Research (SCCPIR), a nationwide network of research and training centers focused on advancing understanding of human reproduction, including ways to treat infertility.
At their lab in California, Dr. Reijo Pera and her colleagues have turned a lens—literally—on the earliest stages of embryonic growth, the first cell divisions in the 24 hours after the sperm has merged with the egg. The information they collect may help improve in vitro fertilization (IVF) and other types of assistive reproduction technologies.

New Technology to Resolve Infertility

Working with a camera attached to a microscope, Dr. Reijo Pera’s team developed ways to film and record the activity of fertilized eggs during their earliest window of development. Her team published the advance in Nature Biotechnology in 2010. That same year, Time magazine named this technological advance External Web Site Policy one of the “top 10 medical breakthroughs of the year External Web Site Policy.”

In a typical IVF process, health care providers examine developing embryos over several days, rating the ones they think are the healthiest and best candidates for transfer to the womb.

The techniques developed in Dr. Reijo Pera’s lab External Web Site Policy allow researchers to assess embryos in a matter of hours, not days, by timing the first divisions of the fertilized cell―into two, four, then eight cells.

“Most embryos are not developmentally competent,” Dr. Reijo Pera said. “If you can select the correct embryo for transfer, you won’t be transferring the ones that are doomed to fail.”

Although science wasn’t always in her sights, Dr. Reijo Pera’s early academic training did sow the seeds of her future career.

“I grew up in Iron River, a small town in northern Wisconsin,” she said. “When I was growing up, girls didn’t have to take science in high school, and so I actually took home economics.”

“I wasn’t particularly interested in science, and as a college student I was a business major working on accounting—keeping track of money.” But taking a course in genetics for non-science majors convinced Dr. Reijo Pera to turn to another kind of accounting.

“Human genetics seemed like a much more interesting problem—keeping track of human genes,” she said. “So it clicked with me naturally, and that really was a turning point in my career.”

Dr. Reijo Pera also found that the long tradition in which senior scientists mentor early-career scientists was something that drew her in.  

At each stage of my career, I have had really great mentors,” she said. “I think I’ve gotten different lessons from each stage of my career, and these people have been very meaningful. I’ve actually gotten a sense as I go on in time, too, that we all mentor the group behind us and we are all mentored by the group that’s ahead of us.”

A Day in Dr. Reijo Pera’s Scientific Life

Today, Dr. Reijo Pera is the George D. Smith Professor of Stem Cell Biology and Regenerative Medicine at Stanford University School of Medicine and Director of the University’s Institute for Stem Cell Biology and Regenerative Medicine. She will join Montana State University as Vice President of Research in January 2014.

And, as an investigator in one of the SCCPIR labs, she also is part of a research community focused on facilitating the transfer of knowledge between the laboratory and clinic, with the goal of improving human reproductive health. Investigators in the SCCPIR program, supported by the NICHD’s Fertility and Infertility Branch, meet regularly to share ideas and trade questions.

In Dr. Reijo Pera’s telling, scientists have two important motivations: curiosity and competition.

“There is something in you that just really wants to know the truth, the answer—and wants to be the first to that truth or that answer. So there is an independent, individualistic side of science,” she said.

But collaboration also comes into play. One of the advantages of the SCCPIR program, she said, is that it gives scientists a chance to be part of a group where they can share their scientific problems and ask for advice.

“It’s really important to get together as a group of scientists that are interested in helping people with infertility,” she said.

Where Clinical Questions and Basic Questions Intersect

Couples often reach out to Dr. Reijo Pera directly with their concerns and their clinical questions.

“One of the problems in infertility is that patients can spend years in the system, trying different options, hoping that they will have a child,” Dr. Reijo Pera said. “If we knew more about the causes, we might be able to help them conceive much more easily.”

In a search for answers, she traces the infertility problem back to the germ cells—the egg and the sperm—and to the genes they hold and the proteins they build.

“The basic studies identify the first genes to come on in development and what genes are mutated in people who have fewer or no sperm or eggs,” Dr. Reijo Pera said.

“The basic questions are: What are the genes involved in infertility? How do they work? What other proteins do they interact with?”

Probing for Answers

Instrumental in the study of these questions are stem cells—cells cultivated in a state from which they can develop into any type of cell in the body, such as muscle, nerve, or blood. 

In 2009, with NICHD funding support, Dr. Reijo Pera led the team that discovered how to transform stem cells into sperm and egg cells. This advance provided a way to develop germ cells in a laboratory dish. The study was published in 2009 the journal Nature.

That advance allows the researchers in her lab to build on earlier discoveries about the biological sources of infertility.

In her work as a postdoctoral fellow at the Massachusetts Institute of Technology’s Whitehead Institute, Dr. Reijo Pera was part of a research team that identified a group of genes closely tied to infertility in men. The DAZ, or deleted in azoospermia, genes are so named because when they are deleted from the Y chromosome, the male cannot make sperm. DAZ genes occur only in humans and in non-human primates.

By manipulating these genes in stem cells, Dr. Reijo Pera and her colleagues are learning more about how DAZ genes function. This work provides clues to understanding how germ cells come to be, and what happens in this process to cause infertility.

“What we have learned is that the more DAZ genes there are, or the higher the activity level of the DAZ genes, the more germ cells are formed,” Dr. Reijo Pera said.

Conversely, when her laboratory inactivated the DAZ genes, fewer germ cells formed. “So the number and the activity in this gene family are really important to fertility,” she said.

“Many clinics now test for these deletions as a possible cause of male infertility,” Dr. Reijo Pera said. “Making that determination is important because knowing it’s a genetic problem can eliminate other possible causes of infertility, such as a tumor.”

What the Future Holds

The past decade has produced significant scientific advances, some specifically related to infertility and others of a broader nature, Dr. Reijo Pera said. Scientists can now manipulate the genome more easily, the introduction of stem cells in infertility research has been a major advance, and the time-lapse imaging that her lab developed could increase the IVF success rate while reducing the number of multiple births.

“Historically it’s been incredibly difficult to turn genes on and off. But a couple of breakthroughs in technology have made us able to knock out any human gene in about a month or two now,” Dr. Reijo Pera said. “So what we have that we never had before is a completely sequenced genome, human [stem] cells that can make any cell type in our body, and a way to turn off genes and turn on genes that is really incredibly powerful. It’s a completely unique time in human history.”

When it comes to the field of stem cell research, Dr. Reijo Pera said that stem cell-based therapies are still being developed. “Cell-based therapies are a way away, but I’m very confident that I’m going to see them in my lifetime. I would guess it’s the next 5 or 10 years.”

And what will be the next big discovery in Dr. Reijo Pera’s field? She said she is not sure she can predict that. “I hope it’s one of ours, though,” she said with a laugh. “Yes, I think it is going to be one of ours.”

(Please note: In line with regulations for federal funding, Dr. Reijo Pera’s laboratory does not use federal funds for human embryo research.)

More Information

Last Updated Date: 12/18/2013
Last Reviewed Date: 12/18/2013
Vision National Institutes of Health Home BOND National Institues of Health Home Home Storz Lab: Section on Environmental Gene Regulation Home Machner Lab: Unit on Microbial Pathogenesis Home Division of Intramural Population Health Research Home Bonifacino Lab: Section on Intracellular Protein Trafficking Home Lilly Lab: Section on Gamete Development Home Lippincott-Schwartz Lab: Section on Organelle Biology