Ryuzo Yanagimachi’s legacy lives on through his groundbreaking work and the personal stories shared by those who knew him best. Known as the “Father of IVF,” Yanagimachi, a pioneering scientist at the University of Â鶹´«Ã½ at ²ÑÄå²Ô´Ç²¹â€™s (IBR), part of the (JABSOM), died in 2023, shortly before receiving the Kyoto Prize in Biotechnology and Medical Technology.

Related UH News story: In memoriam: Ryuzu Yanagimachi, cloning pioneer

Kyoto Prize recipients give speeches at three venues: a grand ceremony in Kyoto, the University of Oxford, and University of California, San Diego (UCSD), where 200 local high school students attend. At UCSD, Steven Ward, who was recruited by Yanagimachi and has served as the IBR director since 2009, spoke on behalf of his late mentor.

“I had known the man for 28 years and worked side by side with him every day for 23. He had 50 years of science and published 400 papers,” Ward said. “I could have spent a week talking about what he did and what he contributed to the field.”

Rather than focusing on Yanagimachi’s scientific achievements, Ward shared personal stories. He remembered his mentor through an oral history, drawing from personal experiences and Life in Science articles Yanagimachi had written over the years.

“Yana was famous enough that people wanted to know his life story in written print. You don’t see this very often,” Ward said. “Those were really interesting because I got a real insight into why he was doing experiments.”

Impact beyond research

Yanagimachi’s influence extended beyond his research. Ward explained that his cloning breakthroughs likely helped save UH’s medical school from closure. In 1999, the UH Faculty Senate voted to merge the school with the School of Public Health.

“When I moved here in 2000, they were talking about closing the medical school. Then Yana’s cloning stuff came up and lit the world on fire,” Ward said.

Ward also emphasized how Yanagimachi’s mentorship encouraged innovation. “He gave his researchers freedom,” Ward said, recalling how Yanagimachi fostered new ideas, including the “Honolulu method” of cloning. “He believed in letting us experiment and explore.”

Ward’s oral history approach was well-received and sparked discussions about changing how future Kyoto Prize speeches are structured.

As JABSOM continues to mourn the loss of their pioneer, Ward intends to continue passing along the history of one of the most influential scientists at UH.

“There are certain things you’ll never get written down that you only have from these oral histories. So it’s important for people to talk to each other,” he said. “It’s important for the younger generation to talk to the older scientists in the community so that they get those things that are never written down.”

In recognition of his contributions, IBR will be renamed the “Yanagimachi Institute for Biogenesis Research,” and a symposium in his honor is planned.

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Having just completed her first semester as a master’s student in the University of Â鶹´«Ã½ medical school’s , Marissa Miyagi was drawn to the field of assisted reproductive technology (ART) research after meeting a woman who was struggling to become pregnant. Through the use of ARTs, the woman was able to conceive and give birth to a child.

“Technologies such as ARTs are a source of hope for patients on days that are long and difficult as they deal with their diagnoses,” said Miyagi. “By continuing this research, I will hopefully contribute to further advancements which will help people have the family they never thought would be possible.”

Miyagi’s research, “Three-Dimensional (3D) Ovarian Tissue Culture Supported by Dextran Hydrogel with Polyethylene Glycol Crosslinker,” was named “Best Graduate Student Poster Presentation” at the hosted by UH ²ÑÄå²Ô´Ç²¹â€™s (JABSOM).

Helping cancer patients

When women undergo chemotherapy or radiation therapy to treat cancer, it can have a negative effect on their fertility. Hormonal treatment is essential for fertility preservation methods that involve the freezing of oocytes (immature egg cells) and embryos. Miyagi is currently investigating the effects of different synthetic hydrogels on follicle growth and oocyte development using an ovarian tissue culture system. She is using the 3D culture system established by the lab of Yukiko Yamazaki, JABSOM associate professor, where Miyagi was previously a volunteer student for the past two years.

“We found that the Dextran-PEG-Link hydrogel successfully supported follicle growth and oocyte development, and that RGD (tripeptide Arg-Gly-Asp) supplementation enhanced these results,” said Miyagi. “This is significant, as using non-animal derived materials is an important step towards applying our system to humans.”

Miyagi is passionate in the fight against cancer, and hopes to enter a career that combines research with patient care.

“I am thankful for the opportunity to be a part of Dr. Yamazaki’s lab, as I am able to combine my passion for helping others with my love of science and innovation. I believe our research can contribute to providing cancer patients with more options in the future.”

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This work is an example of UH ²ÑÄå²Ô´Ç²¹â€™s goal of (PDF), one of four goals identified in the (PDF), updated in December 2020.

The University of Â鶹´«Ã½ at Mānoa has received a $5.3 million grant to continue research at the laboratory that became world-famous for producing mice and other animals that glow green under ultraviolet light. This grant will allow the John A. Burns School of Medicine (IBR) to produce transgenic mice for other researchers seeking medical cures at UH.

The mouse and its pups glowed green because jellyfish genes had been inserted into a mouse embryo to demonstrate the lab’s successful technique for inserting DNA from an unrelated organism into that of another animal. The first green mouse was born, and then she transferred the glowing gene to her pups.

“All along, we’ve been developing new technologies to make us even better,” said Steven Ward, IBR director. “With this grant, we’ll be able to build on our previous 10 years of research to provide genetically altered mice for anybody at UH. These are models that scientists can use for their research—mice with specific diseases or with a certain gene missing or with a gene present so the researchers can see what they can do with it.”

Since mice are the closest animals to humans for biological testing, Ward said, making better mouse models allows scientists to advance cures.

• Read more about the Institute for Biogenesis Research at UH News

This is the third consecutive five-year funding award the IBR has been selected to receive.

The federal funding from the National Institutes of Health’s National Institute of General Medical Sciences will support collaborations between IBR, part of the UH Mānoa , and its reproductive biology departments of and .

—By Tina Shelton

The Y chromosome is a symbol of maleness, present only in males and encoding genes important for male reproduction. But a new study has shown that live mouse progeny can be generated with assisted reproduction using germ cells from males which do not have any Y chromosome genes. This discovery adds a new light to discussions on Y chromosome gene function and evolution. It supports the hypothesis that Y chromosome genes can be replaced by that encoded on other chromosomes.

Two years ago, the University of Â鶹´«Ã½ at Mānoa team led by Monika A. Ward, professor at the , John A. Burns School of Medicine, demonstrated that only two genes of the Y chromosome, the testis determinant factor Sry and the spermatogonial proliferation factor Eif2s3y, were needed for male mice to sire offspring with assisted fertilization. Now, the same team, with a collaborating researcher from France, Michael Mitchell from , Marseille, took an additional step and produced males completely devoid of the entire Y chromosome.

In this new study, scheduled for online publication in the journal Science on January 29, 2016, Ward and her UH colleagues describe how they generated the “No Y” males and define the ability of these males to produce gametes and sire offspring.

Shedding new light on Y chromosome gene function and evolution

“Most of the mouse Y chromosome genes are necessary for development of mature sperm and normal fertilization, both in mice and in humans,” Ward said. “However, when it comes to assisted reproduction, we have now shown that in the mouse the Y chromosome contribution is not necessary.”

The study provides new important insights into Y chromosome gene function and evolution. It supports the existence of functional redundancy between the Y chromosome genes and their homologues encoded on other chromosomes. “This is good news,” Ward said, “because it suggests that there are back-up strategies within genomes, which are normally silent but are capable of taking over under certain circumstances. We revealed two of these strategies by genome manipulation. Whether such alternative pathways would ever be activated without human help, for example in response to environmental changes, is unknown. But it is certainly possible and has already happened for two rodent species which lost their Y chromosomes.”

The development of assisted reproduction technologies (ART) allows bypassing various steps of normal fertilization by using immotile, non-viable, or immature gametes. The newest study as well as Ward’s preceding report (Science 2014 Jan 3;343(6166):69-72) support that in the mouse ROSI is a successful and efficient form or ART. In humans, ROSI is considered experimental due to concerns regarding the safety of injecting immature germ cells and other technical difficulties. The researchers hope that the success in mouse studies may spark the re-evaluation of human ROSI for its suitability to become an option for overcoming male infertility in the future.

Related:

• ; January 5, 2016
• ; November 22, 2013

Read the for more about the discovery.

—By Tina Shelton

Scientists from the have uncovered substantial new knowledge about the function of the Y chromosome gene.

The researchers, including , her two post-doctoral fellows Yasuhiro Yamauchi and Jonathan Riel and PhD student Victor Ruthig, all from of the (IBR), have discovered that only three genes from the Y chromosome are needed for male mice to make sperm able to fertilize oocytes and generate offspring after Intracytoplasmic Sperm Injection (ICSI), a fertilization technique developed at the .

Two years ago the same group reported it successfully obtained offspring from male mice that had only two Y chromosome genes, testis determinant Sry and spermatogonial proliferation factor Eif2s3y. These males did not produce sperm and to achieve fertilization, researchers had to use the immature precursor cells, spermatids, and a technique called Round Spermatid Injection (ROSI). The practice committee of the and the practice committee of the considers ROSI an experimental procedure and do not recommend it for treatment of male infertility. ICSI, however, is used commonly worldwide, with thousands of children born annually.

At IBR, researchers considered which of the Y chromosome genes may be responsible for turning spermatids into sperm. In an international collaboration with Paul Burgoyne’s group from in London, England and Michael Mitchell from , in Marseille, France, they hypothesized that the key gene is Zfy2 (zinc finger protein 2). They added the Zfy2 transgene to males already transgenic Sry and Eif2s3y and lacking the Y chromosome. The resulting males carrying only three Y chromosome genes were producing sperm. These males were not able to reproduce on their own because their sperm number was too low. But when the researchers harvested sperm from the testes and injected them into the oocytes, they become fertilized and when the embryos were transplanted to surrogate mothers, young were born with the same efficiency as from males with normal intact Y chromosome.

Demonstration that three Y chromosome derived genes are enough for a formation of sperm functional in assisted fertilization is an important finding advancing current knowledge about Y chromosome gene function.

“Considering that ICSI, and not ROSI, is commonly used in human infertility treatment, the findings bear translational significance,” said Ward. “Transformation of round spermatids into sperm is a key developmental process gaining a lot of attention due to newly ascribed roles for the sperm epigenome in fertilization and transgenerational inheritance.” Ward’s study points to Zfy2 being a key regulator in this process, including the function of its end product—spermatozoa.

Ward’s team described the discovery in a manuscript published by the leading genetics journal . An accompanying manuscript from Burgoyne and Mitchell groups will appear in PLoS One.

Ward’s research was funded by the National Institutes of Health, National Institute on Minority Health and Health Disparities and the National Institute of General Medical Sciences and the Â鶹´«Ã½ Community Foundation.

—By Tina Shelton