In a groundbreaking development reported on March 8th in Science Advances, scientists at Oregon Health & Science University in the United States have successfully generated in vitro fertilization embryos using mouse skin cells. If this technology proves feasible for clinical applications in the future, it has the potential to revolutionize in vitro fertilization, offering hope to many infertile individuals who have lost sperm or eggs due to diseases, aging, or cancer treatments.
Researchers have successfully generated in vitro fertilized eggs from skin cells. Image source: Oregon Health & Science University.
In 1996, the world witnessed the birth of Dolly the sheep, the first cloned mammal, created through somatic cell nuclear transfer. Scientists extracted the nucleus from a mammary gland cell of a ewe and fused it with an egg cell, resulting in an embryo carrying the ewe's DNA. Since then, scientists worldwide have been exploring methods to generate eggs and sperm in the laboratory, such as using embryonic stem cells to produce sperm and eggs. Last year, Japanese researchers produced eggs from skin cells of male mice, leading to the birth of mice with two fathers.
The lead author of the paper, Shoukhrat Mitalipov, stated that his lab has been developing treatments for patients lacking healthy sperm or eggs over the past two decades. Using donated sperm or eggs may result in children unrelated to their genetic heritage. "Our technology will enable infertile patients to have children genetically related to themselves."
However, previous attempts at such experiments had a success rate of less than 1%, primarily due to eggs discarding half of their chromosomes during development, resulting in abnormal chromosome numbers that hindered healthy embryo development.
Chromosomes are the basic units of the genome and play a crucial role in replicating and distributing genetic information during cell division. In this study, researchers employed a method to induce early cell division, removing the nucleus of the egg first and then transferring mouse skin cells into the mid-phase cytoplasm of mouse oocytes. Subsequent cell division resulted in subcells with reduced ploidy.
Genomic sequencing analysis revealed that the key to success with this method lies in the correct segregation of homologous chromosomes, naturally discarding half of the chromosomes to produce intact haploid genome eggs, ensuring the correct number of chromosomes (one set from each parent) upon fertilization.
"This paper demonstrates how we achieved haploidy," said Mitalipov.
Moreover, this method bypasses the entire process of cell reprogramming, enabling fertilized eggs to be produced within two to three hours, avoiding prolonged culture, during which many harmful genetic and epigenetic changes may occur over months.
Currently, most countries prohibit the use of artificial sperm or eggs to address infertility issues. The first author of the paper, Aleksei Mikhalchenko, stated, "While the clinical application of this technology may still be a decade away and will require thorough evaluation of safety, efficacy, and ethics, its potential to address reproductive-related issues provides broad prospects for future reproductive medicine."
Related paper information: https://doi.org/10.1126/sciadv.adk9001
