In a major breakthrough for male fertility, researchers in China have engineered functioning sperm from mice stem cells.
The scientists converted mouse embryonic stem cells into functional sperm-like cells, which were then inserted into egg cells to generate fertile mouse offspring, according to a study published in the journal Cell Stem Cell.
The researchers said in a statement that their work provides a platform for generating sperm cells that could one day be used to treat male infertility in humans.
Credit: Zhou, Wang, and Yuan et al./Cell Stem Cell 2016
Reproducing the components of life
“Reproducing germ cell development in vitro has remained a central goal in both reproductive biology and reproductive medicine,” study author Jiahao Sha of Nanjing Medical University, said in a press release. “We established a robust, stepwise approach that recapitulates the formation of functional sperm-like cells in a dish. Our method fully complies with the gold standards recently proposed by a consensus panel of reproductive biologists, so we think that it holds tremendous promise for treating male infertility.”
One significant cause of male infertility is the failure of forerunner cells in the testes to go through a kind of cell division known as “meiosis” in order to create functional sperm cells. Multiple research studies have reported the successful production of germ cells from stem cells, but they did not fully assess the viability of the germ cells or supply proof for all essential key points of meiosis.
Recently, a panel of reproductive biologists offered up gold standard criteria for demonstrating that meiosis has occurred in engineered germ cells. For instance, scientists must show proof of the correct nuclear DNA content at particular meiotic stages, normal chromosome number and organization, and the capacity of germ cells to generate viable offspring. Until now, proving the crucial steps of meiosis have occurred has stayed a main obstacle to the generation of viable sperm and egg cells from stem cells.
Proof of concept in mice
In the new study, researchers began by subjecting mouse embryonic stem cells (ESCs) to a chemical mixture that turned the ESCs into primordial germ cells. Next, the scientists modeled the normal tissue environs of these precursor germ cells by subjecting them to testicular cells along with sex hormones like testosterone.
The study team reported that the ESC-derived cells completely went through meiosis, producing sperm-like cells with correct genetic and chromosomal material. To meet last gold-standard verification of meiosis, the scientists injected their cells into mouse egg cells and placed the embryos into female mice. The embryos developed normally and gave rise to good, fertile offspring.
The scientists said they plan to use their system to investigate the molecular parts controlling meiosis. They said they will also test their strategy in other animals such as primates in anticipation of human research. However, before this process is translated to the clinic, risks must be eliminated and ethical concerns concerning the use of embryonic cells should be considered, the study team said.
“If proven to be safe and effective in humans, our platform could potentially generate fully functional sperm for artificial insemination or in vitro fertilization techniques,” Sha said. “Because currently available treatments do not work for many couples, we hope that our approach could substantially improve success rates for male infertility.”
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