25 November 2013

Only two genes can replace the Y chromosome

Geneticists promised conception without the Y chromosome

Copper news

Researchers from the University of Hawaii (Honolulu, USA) for the first time managed to demonstrate that only two genes from the Y chromosome are enough for male mice to conceive healthy offspring. The authors believe that in the future there may be a technique that makes it possible to do without the Y chromosome at all during human reproduction. In addition, the result obtained by the group led by Monika Ward is potentially of great importance for the fight against male infertility, as it shows that the technique of artificial insemination used in experiments with mice is much safer than it has been thought so far. The work is published in the journal Science: Yamauchi et al., Two Y Genes Can Replace the Entire Y Chromosome for Assisted Reproduction in the Mouse. (The press release of the University of Hawaii at Manoa 2 Y genes can replace the entire Y chromosome for assisted reproduction in mice is published on the EurekAlert! – VM website).

The Y chromosome is the sex chromosome of most mammals, including humans. In humans, the Y chromosome consists of more than 59 million pairs of nucleotides and contains more than 86 genes that encode 23 proteins. The most significant gene on the Y chromosome is the SRY gene, which serves as a genetic "switch" for the development of the male-type organism. In addition, the Y chromosome contains genes necessary for the normal formation of sperm.

It is known that an embryo without a Y chromosome normally develops into a female individual, but biologists still wonder whether a male needs a full Y chromosome to conceive healthy male offspring. In their previous studies on mice (Yamauchi et al., Live offspring from mice lacking the Y chromosome long arm gene complement – VM), Ward and her colleagues proved that one SRY gene is not enough for this due to a deficiency of genes responsible for spermatogenesis, but they managed to successfully obtain healthy offspring from males by in vitro fertilization, which completely lacked the long arm of the Y chromosome.

This time, Ward's group used germ cells obtained from male mice in which only two genes were left from the Y chromosome - SRY and the spermatogony proliferation factor Eif2s3y. As the researchers found, Eif2s3y is the only Y-chromosome gene required to maintain the process of spermatogenesis in mice. Its presence makes it possible to bring this process to the stage of formation of round spermatid – haploid precursor cells, which at the stage of spermiogenesis differentiate into mature spermatozoa.

The resulting round spermatids were then fertilized in vitro eggs using the method of intracytoplasmic injection (ROSI).

Some of them developed into embryos, which were then implanted into the wombs of females. As a result of this procedure, 9 percent of pregnancies ended with the birth of healthy offspring (in the case of males with a full Y chromosome, this figure is 26 percent).

ROSI is an experimental IVF procedure used if spermatogenesis ends in men at the level of spermatid formation. However, the consequences of its use are of concern to specialists due to the danger of genetic defects in offspring due to immaturity of spermatids. In particular, these concerns are related to the underdevelopment of fundamental genetic processes in these cells, primarily genomic imprinting – the dependence of gene expression on which parent it is transmitted. Numerous genetic diseases are associated with imprinting errors.

As Robin Lovell-Badge, an evolutionary geneticist from the National Institute of Medical Research (London, UK), stated in an interview with the journal Nature (Mice with just two 'male' genes father babies), the results of the Ward group, in principle, can dispel existing concerns about the use of the ROSI technique in humans. "The fact that with the help of ROSI, using only two genes, normal offspring were obtained in mice suggests that concerns about possible imprinting errors in humans may be groundless, which is important for men with a defective Y chromosome and for those with impaired sperm formation," – believes Lovell-Badge.

Ward and her colleagues are currently working to identify a minimal pool of genes in the human Y chromosome that is sufficient to conceive healthy offspring. Ward does not rule out that in the future it will be possible to do without the Y chromosome in this case in case of its defect. This can happen if genes interacting with Y-chromosome genes are found on other chromosomes, then activation of such partner genes can theoretically completely replace their functions.

Portal "Eternal youth" http://vechnayamolodost.ru25.11.2013

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