Experimental approach might provide insights to support human fertility

Web edition : Thursday, October 4th, 2012

Some baby mice born in Japan are living proof that mouse stem cells taken from embryos or created by reprogramming fetal tissue can be used to make viable egg cells.

Researchers had already created functional sperm from stem cells, and some groups have reported making eggs, or oocytes, but those had never been shown to produce offspring. Now, Mitinori Saitou of Kyoto University in Japan and colleagues have coaxed mouse stem cell to make eggs that produce normal, fertile offspring, the researchers report online October 4 in Science.

This is really pioneering research, says Charles Easley, a reproductive stem cell biologist at Emory University School of Medicine in Atlanta.

The researchers have gone a step beyond making cells that merely look like eggs in a lab dish. This paper produces something that looks like oocytes, smells like oocytes and tastes like oocytes in a way no one has done before, says David Albertini, a reproductive scientist at the University of Kansas Medical Center in Kansas City.

While the evidence that the Japanese researchers have transformed mouse stem cells into functional female gametes is compelling, Albertini doesnt think the feat will be repeated with human stem cells because they are far less flexible than their mouse counterparts. The new technology might provide a way to test the effect that chemicals in the environment may have on fertility and give scientists new information about how eggs age, possibly leading to fertility-extending treatments, he says.

In the new study, Saitou and colleagues started with stem cells from very early mouse embryos as well as stem cells reprogrammed from fetal cells, known as induced pluripotent stem cells. Saitous team manipulated the activity of a few genes in the stem cells to turn them into cells that resemble precursors of gametes, as eggs and sperm are sometimes known.

These primordial germ celllike cells, as they are called, were mixed with support cells from an embryonic ovary and then transplanted into adult mice. Once the precursor cells had developed into oocytes, the researchers pulled them out and fertilized them in the lab before implanting the resulting embryos in female mice.

The oocytes made from either type of stem cell produced mouse pups 3.9 percent of the time. That rate is lower than for primordial germ cells taken directly from mouse embryos, which the researchers found produced pups 17.3 percent of the time. Oocytes taken from the ovaries of 3-week-old mice generated offspring 12.7 percent of the time. Female pups resulting from stem cellderived eggs grew up to become fertile adults, the researchers report.

Here is the original post:
Mouse stem cells yield viable eggs

Mouse pups created using lab-made eggs went on to be fully fertile themselves.

Courtesy of Katsuhiko Hayashi

Japanese researchers have coaxed mouse stem cells into becoming viable eggs that produce healthy offspring1. The work provides a powerful tool to study basic elements of mammalian development and infertility that have long been shrouded in mystery.

People have been trying to make sex cells from embryonic stem cells and from pluripotent cells for years, says Evelyn Telfer, a reproductive biologist at the University of Edinburgh, UK. Theyve done it and theyve done it really well.

Stem-cell scientists have derived many types of cells from stem-cell precursors, but have struggled with sex cells. These cells have significantly more complex developmental programmes, in part because of the difference in the way they divide. Most cells in the body undergo mitosis, in which both sets of chromosomes are copied, but sex cells are produced by meiosis, which results in cells containing a single copy of each chromosome.

Last year, the same team from Mitinori Saitous lab at Kyoto University in Japan successfully used mouse stem cells to make functional sperm2. Whereas sperm cells are some of the simpler cells in the body, oocytes are much more complex.

It was always believed that making sperm was probably easier, says Davor Solter, a developmental biologist at the Institute of Medical Biology in Singapore, who was not involved with the study. The oocyte is the thing which makes the whole of development possible.

In the latest study, published today in Science, Saitou and his colleagues started with two cell types: mouse embryonic stem cells and induced pluripotent stem cells, which can be derived from adult cells. Just as in the earlier sperm study, they used a cocktail of signalling molecules to transform the stem cells first into epiblast cells and then into primordial germ cells (PGCs), both egg precursors. Whereas male PGCs could be injected directly into infertile male mice to mature into sperm, the female version required further coddling.

The researchers isolated embryonic ovary tissue that did not contain sex cells and then added their lab-made PGCs to the dish. The mixture spontaneously formed ovary-like structures, which they transplanted into female mice. After four weeks, the stem-cell-derived PGCs had matured into oocytes. The team fertilized them and transplanted the embryos into foster mothers. The offspring that were produced grew up to be fertile themselves.

PGCs are scarce and difficult to isolate from mice, so researchers know little about their regulation, says Saitou. As PGCs develop into sperm or egg cells, certain genes are silenced in a process called genomic imprinting. Although this is crucial for development, little is known about how it starts or how genes are selected for silencing.

Excerpt from:
Mouse stem cells lay eggs

4 October 2012 Last updated at 18:31 ET By James Gallagher Health and science reporter, BBC News

Stem cells made from skin have become "grandparents" after generations of life were created in experiments by scientists in Japan.

The cells were used to create eggs, which were fertilised to produce baby mice. These later had their own babies.

If the technique could be adapted for people, it could help infertile couples have children and even allow women to overcome the menopause.

But experts say many scientific and ethical hurdles must be overcome.

Stem cells are able to become any other type of cell in the body from blood to bone, nerves to skin.

Last year the team at Kyoto University managed to make viable sperm from stem cells. Now they have performed a similar feat with eggs.

They used stem cells from two sources: those collected from an embryo and skin-like cells which were reprogrammed into becoming stem cells.

I just thought wow! The science is quite brilliant

The first step, reported in the journal Science, was to turn the stem cells into early versions of eggs.

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Skin cells become 'grandparents'