Lab-made sperm used to breed healthy mice

Helen Robertson

Progress Educational Trust

29 February 2016

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[BioNews, London]

Scientists in China have used stem cells to create rudimentary sperm that successfully fertilised mouse eggs to produce healthy offspring.

The mice that were born from this process went on to give birth to healthy offspring of their own, and it is hoped that this work could form the basis of future treatments for male infertility.

'We established a robust, stepwise approach that recapitulates the formation of functional sperm-like cells in a dish,' said Dr. Jiahao Sha of Nanjing Medical University, one of the two lead authors of the paper, published in Cell Stem Cell. 'Our method fully complies with the gold standards recently proposed … so we think that it holds tremendous promise for treating male infertility.'

The work is believed to be the first to meet the 'gold standards' put forward in 2014 for work in this area. In order to meet this requirement, the authors first had to demonstrate that the germ cells they created had undergone all the correct stages of meiosis – the process by which cells divide to produce sperm or egg cells with half the chromosomes of other cells in the body. They also had to demonstrate that the chromosomes in these cells were normal and that healthy offspring could be produced.

'The achievements of this paper are very remarkable. I'm not aware of another group having progressed this far,' Professor John Schimenti of Cornell University in Ithaca, New York, one of the researchers who defined the gold standards, told New Scientist.

The team first created early sperm precursor cells, known as primordial germ cells, by exposing mice embryonic stem cells to a special chemical cocktail. These primordial germ cells were then put in an artificial environment designed to mimic the developmental conditions of sperm. This required cells taken from testicular tissue of newborn mice, and sex hormones including testosterone.

This resulted in round cells which lack a tail and cannot swim, and are very similar to spermatids, which mature into sperm in normal development. These were injected into normal mouse eggs, which went on to produce six healthy mice. At 15 months these were mated and produced normal offspring of their own.

Infertility affects around 15 percent of couples, with one-third of these cases being attributed to the man. A number of studies in recent years have focused on the possibility of inducing sperm in the lab for use in in vitro fertilisation or artificial insemination.

'If proven to be safe and effective in humans, our platform could potentially generate fully functional sperm for artificial insemination or in vitro fertilisation techniques,' said Dr Sha.

While the results of this study are encouraging, some scientists remain sceptical about the technique.

The artificial germ cells developed much more rapidly than would be expected normally, meaning that the resulting spermatids could behave erratically. In addition, the offspring born using the spermatids could 'still contain defects or problems that do not manifest themselves until later', Dr. Allan Spradling, a reproductive biologist at the Carnegie Institution for Science who was not involved in the study, told Nature News.

The study used mouse embryonic stem cells as a starting point, but other studies are investigating using stem cells derived from adult cells, which could in principle be taken from infertile adult men.

'The implications for managing human infertility or onco-fertility are there, but I think they are considerably further off in the future,' Dr. Mary Ann Handel, a biologist at the Jackson Laboratory in Maine and a co-author of the gold standards, told the Guardian. 'Of course, as for any exciting advance, the real "gold standard" will be independent replication of this work by other groups.'

Reproduced with permission from BioNews, an email and online sources of news, information and comment on assisted reproduction and genetics.