By Kevin Wilger

Katsuhiko Hayashi of Osaka University and Kyushu University has reported that his research team derived functional mouse egg cells (oocytes) solely from male stem cells. Hayashi first described the scientific work in early March at the Third International Summit on Human Genome Editing held at the Francis Crick Institute in London. The next week his research team published the details of the experiment in Nature, complete with images of adult “bi-paternal” mice made from the oocytes. The authors write that the purpose of the experiment was to study infertility caused by chromosomal disorders and that it “opens the possibility of bi-paternal reproduction.”

The first aim of the investigation was to demonstrate that male stem cells can become behaviorally like female stem cells in regard to generating oocytes. Previous work by the authors had shown that pluripotent stem cells with male chromosomes were not able to generate oocytes. Therefore, the Y chromosome was removed from the cells by multiple “passages,” which are transfers of the cells to a fresh medium. According to the authors, a small percentage of male pluripotent stem cells will spontaneously lose their Y chromosome after multiple cell passages. Next, they isolated those X-only cells and performed additional passages with an inhibitor called reversine, which helped to promote X chromosome duplication. Finally (and a few steps later), these X-duplicated stem cells were able to be differentiated into oocytes at a rate that was not significantly different from that of native female embryonic stem cells.

The authors ultimately aimed to show that male stem cells could be used to generate functional adult offspring. Fibroblasts (cells that contribute to connective tissue) were taken from the tail tips of eight-week-old male mice and were converted to X chromosome-duplicated cells and oocytes as described above. These oocytes were fertilized with non-modified sperm and grown until the two-cell embryo stage. The embryos were transferred to surrogate mothers, and seven out of the 630 transferred embryos survived to be mouse pups. Impressively, the pups developed to adulthood and were themselves able to produce offspring.

The authors believe that their approach to bi-paternal reproduction has unique advantages compared with similar studies, since the offspring did not have any abnormalities, premature death, or loss of fertility. In future work, the team aims to generate both sperm and eggs from a single line of male stem cells to fertilize and grow offspring. However, at the time of publication, the authors were unsuccessful in over 1,500 attempts at fertilization. 

The results of the experiment have garnered significant media attention across the globe and raise the question of their applications in human reproduction. For example, an article in the Guardian contends that the experiment is “a development that opens up radical new possibilities for reproduction,” which “[raises] the tantalising prospect of same-sex male couples being able to have a biological child together in the future.” The article also notes that Hayashi himself would support the use of the technology for two males to create a child in this manner, if it were shown to be safe.

A 2022 analysis of regulations in Japan found that experiments which propose to use human sperm and eggs generated from stem cells to fertilize and reproduce are “clearly prohibited.” The International Society of Stem Cell Research’s most recent guidelines prohibit the use of sperm and eggs “differentiated from human stem cells for reproduction.” These experiments are proscribed because they are currently unsafe (category 3A experiments) and not because of lack of scientific rationale or ethical concerns (category 3B experiments). The guidelines do not address the specific concern of bi-paternal production.

The Catholic Church has consistently defended the humanity of embryos and their rights to be created in the conjugal acts of loving husbands and wives and to be gestated by their own mothers. Embryonic humans are not commodities to be created for the sole purpose of satisfying the desire of two men to both be the biological parents of the same child. To do so is to commit a grave act against the dignity of the human person and to reject of God’s plan for creation.

Kevin Wilger is a research engineer in Lafayette, Indiana.