A new study reveals a new approach to treat infertility

A new research from Oregon Health & Science University showed the scientific basis of a promising methodology for treating infertility: transforming a skin cell into an egg capable of generating viable embryos.

The study, published in the journal Science Advances, documented the process of in vitro gametogenesis (IVG) in a mouse model, outlining the initial stages of a technique involving the transfer of a skin cell nucleus into a donated egg lacking its own nucleus. Through experimentation in mice, researchers induced the skin cell nucleus to halve its chromosomes, enabling fertilization by a sperm cell to produce a viable embryo.

“The goal is to produce eggs for patients who don’t have their own eggs,” said senior author Shoukhrat Mitalipov, Ph.D., director of the OHSU Center for Embryonic Cell and Gene Therapy.

Rather than attempting to differentiate induced pluripotent stem cells, or iPSCs, into sperm or egg cells, OHSU researchers focused on a technique based on somatic cell nuclear transfer, in which a skin cell nucleus is transplanted into a donor egg stripped of its nucleus. The method offers potential for women with advanced maternal age or those unable to produce viable eggs due to various reasons, including cancer treatment.

In the study, the researchers followed three steps: first, they transplanted the nucleus of a mouse skin cell into an egg devoid of its own nucleus. Next, stimulated by cytoplasm, the implanted nucleus shed half of its chromosomes, similar to the process of meiosis. This crucial step yields a haploid egg with a single set of chromosomes. Finally, the researchers fertilized the newly formed egg with sperm through in vitro fertilization, resulting in a diploid embryo with two sets of chromosomes, ensuring healthy offspring with balanced genetic contributions from both parents.

The findings revealed that the skin cell’s nucleus segregated its chromosomes each time it was implanted in the donor egg. In rare cases, this happened perfectly, with one from each pair of matching egg and sperm chromosomes.

“We’re skipping that whole step of cell reprogramming,” said co-author Paula Amato, M.D., professor of obstetrics and gynecology in the OHSU School of Medicine. “The advantage of our technique is that it avoids the long culture time it takes to reprogram the cell. Over several months, a lot of deleterious genetic and epigenetic changes can happen.”

“This gives us a lot of insight,” she said. “But there is still a lot of work that needs to be done to understand how these chromosomes pair and how they faithfully divide to actually reproduce what happens in nature.”

Reference: ALEKSEI MIKHALCHENKO, NURIA MARTI GUTIERREZ, DANIEL FRANA, ZAHRA SAFAEI, CRYSTAL VAN DYKEN, YING LI, HONG MA, AMY KOSKI, DAN LIANG, AND SHOUKHRAT MITALIPOV; Journal: Science Advances; DOI: 10.1126/sciadv.adk9001