Generation of rat offspring from ovarian oocytes by cross-species transplantation

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The idea of maturing oocytes in the ovary to produce offspring has been implemented in various ways. One such method, ovarian transplantation, is a relatively simple procedure for obtaining eggs, compared to in vitro culture of ovaries and follicles. However, it is still difficult to transplant ovaries into cellular immunodeficient mice and produce offspring from the eggs grown in the mice.

In order to produce offspring from xenotransplanted ovaries, Japanese researchers at Niigata University and University of Toyama conducted a study to establish a system to produce offspring from eggs obtained by transplanting rat ovaries into mice.

The researchers implanted rat ovaries under the renal capsules of immunodeficient mice and confirmed their viability. Then, they administered hormones related to oocyte development and succeeded in obtaining mature rat eggs. These eggs were found to develop normally when fertilized in vitro and to become embryos or offspring when transplanted into the rat uterus. When the ovaries from rats expressing a fluorescent protein throughout the body were used for donner, resulting in rat offspring expressing the fluorescent protein. It was confirmed that this genetic trait is inherited to the next generation. These results were published in Scientific Reports on August 29, 2024.

“There have been reports on the acquisition of eggs and embryos using interspecies ovarian transplantation into mouse recipients, but there are no successful cases of offspring production. In this study, we were able to produce fertilized eggs and offspring, overcoming this tough challenge,” says Runa Hirayama, a graduate student at the University of Toyama.

An important point in producing offspring by this method was to obtain mature eggs from the transplanted ovaries. After administering hormones to transplanted mice, both mature and immature eggs were obtained from the transplanted ovaries. Mature eggs could be fertilized immediately after acquisition, while immature eggs needed to be matured before fertilization. In this study, we found that the percentage of eggs that matured and were cultured in vitro and produced offspring was very low, and that the maturity when the eggs were obtained from the ovary was critical for increasing the birth rate.

“This new offspring production system has the potential for the generation of genetically modified rats and could become one of the most effective methods of animal offspring production,” says Dr. Hiroaki Taketsuru of Niigata University. This achievement will not only facilitate the production of genetically modified animals, but also be applied to the creation of offspring of all types of animals, as well as reproductive medicine.

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