Highlights in this article:

Dr. Hayashi’s research group has discovered a groundbreaking technique that allows them to convert male XY chromosomes into female XX chromosomes, without the need for additional chromosomes. The technique has successfully created healthy eggs in female mice and enabled the production of offspring using only male genetic material. This discovery could revolutionize infertility treatment caused by chromosome abnormalities and provide new options for same-sex couples to have biological children.

Background:

The X and Y chromosomes are a pair of sex chromosomes that determine an individual’s biological sex. Typically, females have two X chromosomes (XX), while males have one X and one Y chromosome (XY). The sex chromosomes are responsible for encoding genes that contribute to the development of primary and secondary sexual characteristics, as well as regulating reproductive function.

The X chromosome is larger and contains more genetic material than the Y chromosome. It carries a variety of genes that are involved in a range of functions, such as immune system regulation, vision, and brain development. Many X-linked genes are important for normal development and function of the body, including the regulation of hormones and the development of sexual characteristics.

On the other hand, the Y chromosome is smaller and contains fewer genes than the X chromosome. It primarily encodes genes that are involved in male sexual development and fertility. The SRY gene, located on the Y chromosome, triggers the development of male sex organs and secondary sexual characteristics during fetal development. Other genes on the Y chromosome are involved in sperm production and maturation.

The inheritance of sex chromosomes follows a predictable pattern. Females always pass on an X chromosome to their offspring, while males can pass on either an X or a Y chromosome. This means that the sex of the offspring is determined by the sex chromosome inherited from the father. For example, if a male passes on his X chromosome, the offspring will be female (XX), while if he passes on his Y chromosome, the offspring will be male (XY).

While the X chromosome is relatively stable and does not undergo significant changes, the Y chromosome has a higher mutation rate and is more prone to loss of genetic material. This can lead to variations in Y chromosome structure between individuals and populations, which can have implications for genetic disease risk and evolutionary studies. In some rare cases, individuals may be born with variations in their sex chromosomes, such as XXY (Klinefelter syndrome) or XYY. These conditions can cause a range of physical and developmental symptoms, depending on the specific genetic variation and individual factors. Understanding the genetics and biology of sex chromosomes is important for advancing our understanding of human biology and health.

Discovery:

Dr. Hayashi’s research group has developed a technique that converts stem cells’ sex by removing the Y chromosome and duplicating the X chromosome, resulting in cells with maternally inherited X chromosomes. They discovered that having two maternal X chromosomes did not significantly affect oocytes’ transcriptome, but they identified a differentially expressed gene called Parp8. The researchers suggest that Parp8 genes should be monitored since they may be susceptible to X chromosome homozygosity. They also found that individual autosomes have a distinct propensity for missegregation, which is a significant finding in genetics.

Dr. Hayashi’s research group has used sex-converted stem cells to produce functional oocytes that gave rise to bipaternal offspring after fertilization and transplantation. This technique could help overcome infertility caused by sex chromosome or autosomal disorders, but the challenge will be to produce both eggs and sperm from a single XY stem cell in vitro. The discovery of a technique that converts male XY chromosomes into female XX chromosomes is groundbreaking and has the potential to revolutionize infertility treatment and provide new options for same-sex couples to have biological children. Understanding the genetics and biology of sex chromosomes is essential in advancing human biology and health.

For more information:

Nature 2023 3/15

https://www.nature.com/articles/s41586-023-05834-x

Generation of functional oocytes from male mice in vitro

Dr. Hayashi’s website:

https://www.med.osaka-u.ac.jp/eng/introduction/research/genome/germline