Researchers uncover two reprogramming stages in the development of gametes

Dec 17, 2012 by Bob Yirka report

(Phys.org)—A research team from the University of California has identified two reprogramming events that occur during the development of oocytes and sperm leading to the formation of gametes in humans. In studying aborted human fetuses, the researchers, as they describe in their paper published in the journal Nature Cell Biology, found they were able to isolate oocytes and sperm and then to follow their development into gametes.

This new research is part of an effort to understand why approximately 10 percent of people are born infertile. Scientists believe that it's possibly due to problems that occur during the very earliest stages of fetal development. In the first few weeks after conception – after oocytes in females and sperm in males appear – the development of balls of cells known as come about. Up till now, most research focusing on the development of gametes has been done on mice, however, due to the sensitivity of studying actual human early fetal development – to do so generally means the destruction of the fetus. In this new research, the team from California received permission to use samples of aborted fetuses from the University of Washington's Birth Defects Research Laboratory.

By studying fetal samples taken at different stages of development (from 6 to 20 weeks) the team was able to piece together the developmental process that leads to the fully developed gamete. In looking at the developmental process the team discovered two distinctive events occurring – one before six weeks, and the other after. Both involved reprogramming – changes to the structure of that have an impact on how genes in them are expressed. This finding doesn't explain why some people are born infertile, of course, but it does provide a road map of sorts that researchers can use to trace the development of the cells that are responsible for reproduction later in life.

Also, in comparing 6 week old germ cells that had been raised in their lab with those grown naturally inside the womb, they found that the two didn't match, suggesting that a process occurs in utero causing the to change, that is still not understood.

Explore further: Fungus deadly to AIDS patients found to grow on trees

More information: The ontogeny of cKIT+ human primordial germ cells proves to be a resource for human germ line reprogramming, imprint erasure and in vitro differentiation, Nature Cell Biology, (2012) doi:10.1038/ncb2638

Abstract
The generation of research-quality, clinically relevant cell types in vitro from human pluripotent stem cells requires a detailed understanding of the equivalent human cell types. Here we analysed 134 human embryonic and fetal samples from 6 to 20 developmental weeks and identified the stages at which cKIT+ primordial germ cells (PGCs), the precursors of gametes, undergo whole-genome epigenetic reprogramming with global depletion of 5mC, H3K27me3 and H2A.Z, and the time at which imprint erasure is initiated and 5hmC is present. Using five alternative in vitro differentiation strategies combined with single-cell microfluidic analysis and a bona fide human cKIT+ PGC signature, we show the stage of cKIT+ PGC formation in the first 16 days of differentiation. Taken together, our study creates a resource of human germ line ontogeny that is essential for future studies aimed at in vitro differentiation and unveiling the mechanisms necessary to pass human DNA from one generation to the next.

Related Stories

Scientists turn stem cells into precursors for sperm, eggs

Oct 28, 2009

Human embryonic stem cells derived from excess IVF embryos may help scientists unlock the mysteries of infertility for other couples struggling to conceive, according to new research from the Stanford University School of ...

USC researchers explore genetic causes for male infertility

Dec 12, 2007

Researchers at the University of Southern California (USC) suggest epigenetics, or the way DNA is processed and expressed, may be the underlying cause for male infertility. The study will be published in the Dec. 12 issue ...

Researchers Reprogram Human Induced Pluripotent Stem Cells

Jan 27, 2009

For the first time, UCLA researchers have reprogrammed human induced pluripotent stem (iPS) cells into the cells that eventually become eggs and sperm, possibly opening the door for new treatments for infertility using patient-specific ...

Maelstrom quashes jumping genes

Aug 11, 2008

Scientists have known for decades that certain genes (called transposons) can jump around the genome in an individual cell. This activity can be dangerous, however, especially when it arises in cells that produce eggs and ...

Recommended for you

Some anti-inflammatory drugs affect more than their targets

14 hours ago

Researchers have discovered that three commonly used nonsteroidal anti-inflammatory drugs, or NSAIDs, alter the activity of enzymes within cell membranes. Their finding suggests that, if taken at higher-than-approved ...

Researchers discover new strategy germs use to invade cells

Aug 20, 2014

The hospital germ Pseudomonas aeruginosa wraps itself into the membrane of human cells: A team led by Dr. Thorsten Eierhoff and Junior Professor Dr. Winfried Römer from the Institute of Biology II, members of the Cluster ...

Progress in the fight against harmful fungi

Aug 20, 2014

A group of researchers at the Max F. Perutz Laboratories has created one of the three world's largest gene libraries for the Candida glabrata yeast, which is harmful to humans. Molecular analysis of the Candida ...

How steroid hormones enable plants to grow

Aug 19, 2014

Plants can adapt extremely quickly to changes in their environment. Hormones, chemical messengers that are activated in direct response to light and temperature stimuli help them achieve this. Plant steroid ...

User comments : 0