Scientists have achieved a scientific breakthrough that could open new horizons for treating male infertility, after they succeeded in developing a laboratory model that mimics sperm growth inside a miniature testicle, using human blood cells.
Many men of reproductive age suffer from fertility problems, often due to a defect in germ cell development, the process by which embryonic cells grow into sperm or eggs.
The lack of accurate laboratory models that mimic this process has been a long-standing obstacle to the development of effective treatments.
In a recent study published in the journal Cell Stem Cell, scientists devised a scientific formula to convert cells derived from human blood into progenitor cells (unspecialized biological cells similar to stem cells) for sperm, within a three-dimensional environment resembling a normal testicle.
Scientists started with induced pluripotent stem cells (iPSCs) taken from humans and macaque monkeys, which are cells that can be transformed into almost any cell type.
Using specific chemical signals, they converted them into primitive germ cells in the laboratory, then added supporting cells from mouse embryos to provide the right environment for their growth. These cells spontaneously assembled to form a three-dimensional structure that mimics a real testicle.
Within this miniature testis, spiral-shaped seminiferous tubules began to appear, resembling in appearance and genetic activity true human germ cells in their early stages.
It is worth noting that sperm development is a long and complex process that begins before birth and continues throughout life; any error in this process can lead to infertility or birth defects. While rodent models are useful in studying reproduction, they do not accurately reflect primate evolution due to significant structural and molecular differences.
To overcome this obstacle, the team developed a multi-stage system for growing and maturing primate sperm cells outside the body. They started with stem cells from human blood and macaque monkey tissue, then converted them into primitive sperm cells.
Then they added supporting cells from the testes of mice to form the miniature testicular structure, and then implanted it into the kidneys of genetically modified mice to ensure its survival and blood supply, allowing it to grow for 8 to 9 months, a much longer period than could be achieved in ordinary laboratory dishes.
In this way, the researchers succeeded for the first time in generating immature macaque sperm cells from stem cells, which were up to 97% identical to normal cells from living monkeys and humans.
The study also revealed two key proteins, NANOS3 and DND1, that play a vital role in maintaining the viability of germ cells and preventing them from transforming into other cell types. It further showed that retinoic acid, a derivative of vitamin A, is the catalyst that initiates the maturation process in these cells.
This achievement represents a solid foundation for understanding germ cell development in primates, and provides a valuable laboratory model for studying the genetic and evolutionary causes of male infertility, and for testing future treatments effectively and safely before testing them on humans.
