Sperm created from stem cells offer hope in cases of male infertility
Functioning sperm that could one day be used to treat infertility in men have been created in a laboratory by scientists in China, according to a report in Cell Stem Cell.The Centers for Disease Control and Prevention (CDC) define infertility as “not being able to get pregnant after 1 year of unprotected sex.”
Globally, up to 15% of couples are unable to have children, with 1 in 3 cases being due to male infertility.
In the US, about 6% of married women aged 15-44 years are unable to conceive within a year of trying, and around 12% of all American women aged 15-44 years have difficulty either becoming pregnant or carrying a pregnancy to term.
A CDC study in 2002 found that male infertility caused 7.5% of all sexually experienced men under 45 years to seek help at some time, 14% of whom were diagnosed with sperm or semen problems.
Male infertility often results because meiosis does not happen. Meiosis is a type of cell division that occurs in the precursor germ cells in the testes. Without it, functional sperm cells cannot form. Successful meiosis proven for the first time
Scientists have previously generated germ cells from stem cells, but the functionality of the germ cells was not proven, nor was there evidence of all the key hallmarks of meiosis.
It was only recently that a panel of reproductive biologists proposed gold standard criteria to prove that the major events of meiosis have taken place in engineered germ cells.
Acceptable evidence includes proof that the DNA has correct nuclear content at specific meiotic stages, that there is a normal number of chromosomes, that the chromosomes are correctly organized, and that the germ cells can produce viable offspring.
Until now, scientists have had difficulty completing all the essential steps of meiosis successfully.
This has remained a major obstacle to producing functional sperm and egg cells in vitro.
Reproducing germ cell development in this way has therefore been a key goal for both reproductive biologists and reproductive medicine.
Now, a team of researchers from Nanjing Medical University has carried out a robust, step-by-step process that not only coaxed embryonic stem cells from mice to turn into functional sperm-like cells, but also injected them into egg cells to produce fertile mouse offspring.
The team started by exposing mouse embryonic stem cells (ESCs) to a chemical cocktail that caused the ESCs to turn into primordial germ cells. Sperm lead to two generations of offspring
Next, the researchers exposed the cells to testicular cells – as well as sex hormones such as testosterone – in order to recreate the natural tissue environment of the cells.
Under these conditions, complete meiosis occurred, producing sperm-like cells with correct nuclear DNA and chromosomal content. When injected into mouse egg cells, embryos developed. The team transferred the embryos into female mice, where they progressed normally and produced healthy, fertile offspring, which later gave birth to the next generation.
Co-senior author Jiahao Sha says: “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.”
Based on these findings, the researchers next plan to examine the molecular mechanisms that control meiosis and to test their approach in other animals such as primates in anticipation of human studies.
However, for the technique to become a clinical reality, a number of potential risks and ethical concerns about the use of embryonic cells must first be addressed.