Role of the mitochondrial genome in assisted reproductive technologies

Mitochondria play a pivotal role in cellular metabolism and are important determinants of embryonic development. Mitochondrial function and biogenesis rely on an intricate coordination of regulation and expression of nuclear and mitochondrial genes. For example, several nucleus-derived transcription factors, such as mitochondrial transcription factor A, are required for mitochondrial DNA replication. Mitochondrial inheritance is strictly maternal while paternally-derived mitochondria are selectively eliminated during early embryonic cell divisions. However, there are reports from animals as well as human patients that paternal mitochondria can occasionally escape elimination, which in some cases has led to severe pathologies. The resulting existence of different mitochondrial genomes within the same cell has been termed mitochondrial heteroplasmy. The increasing use of invasive techniques in assisted reproduction in humans has raised concerns that one of the outcomes of such techniques is an increase in the incidence of mitochondrial heteroplasmy. Indeed, there is evidence that heteroplasmy is a direct consequence of ooplasm transfer, a technique that was used to 'rescue' oocytes from older women by injecting ooplasm from young oocytes. Mitochondria from donor and recipient were found in varying proportions in resulting children. Heteroplasmy is also a byproduct of nuclear transfer, as has been shown in studies on cloned sheep, cattle and monkeys. As therapeutic cloning will depend on nuclear transfer into oocytes and the subsequent generation of embryonic stem cells from resulting blastocysts, the prospect of mitochondrial heteroplasmy and its potential problems necessitate further studies in this area.

The Newspaper Article Is Funnier Than The Signboard

Present-day Love Story

Rotunda Management Meetings

Hi friends, we are rushing towards another weekend and also on the cusp of getting our fresh re-certification audit done for the ISO 9001-2000 standards for our clinic. Everyone is working hard towards the goal. Just found a nice cartoon in NY times about our management meetings.
Have a nice weekend, folks.

Lab on a Chip Medical Breakthrough

It's common knowledge that to carry out genetic tests, one would need expensive, state-of-the-art laboratory. But that might soon change thanks to a group of Canadian scientists who've developed a "lab-on-a-chip" device to conduct these tests. What is interesting about the device is that it's supposed to be portable, inexpensive, and efficient.

Hailing from the University of Alberta; Professor Christopher Backhouse and Professor Linda Pilarski (Department of Oncology), along with research student, Govind Kaigala, have developed a $1,000 device the size of a shoebox that can conduct genetic tests and deliver results in less than half an hour.

Elaborating on the innovation, the researchers said that miniaturization is the key factor that has drastically brought down the cost of this gadget.

The Canadian Press quoted Professor Backhouse as saying that like computers, which in their early days, were inaccessible; somewhat like million-dollar beasts who formed a roomful, yet one needed a Ph.D. to to be able to operate one of them.

Similarly, the Professor said Life Science technologies do exist but aren't being utilized optimally because they're very expensive. Hence, the key to this mini-laboratory was to integrate, shrink, and automate. The ability of the device to implement a very wide range of tests on a standard platform quickly and inexpensively would make it indispensable for the future.

The research team believes that their miniature lab-on-a-chip will provide Cancer patients with quick genetic tests, in turn speeding up treatment processes. The team also believes the device may be useful in finding genetic signatures for particular viruses or bacteria or for testing the quality of water, and so on.

Sperm From Female Stem Cells

British scientists have created early-stage, human sperm from female stem cells, according to a news report in New Scientist magazine. It is claimed that the research will pave the way for same sex couples to have children that are genetically their own. However, other scientists are sceptical that this procedure would ever be possible.
Professor Karim Nayernia at the University of Newcastle initially fertilised mice with sperm derived from embryonic stem cells (ESCs) in 2006, which gave rise to seven pups, six of which survived. In more recent work, he took human male stem cells from bone marrow and formed 'spermatogonia', primitive sperm cells that can form mature sperm cells by going through a process called meiosis. Nayernia has now apparently done the same using human female stem cells, work that has yet to be published.
The next stage in the process would be to make these primitive sperm cells undergo meiosis, which Nayernia claims he has started to do. The result could be that female eggs are fertilised by 'female' sperm, thereby eradicating the need for male gametes. However, Dr Robin Lovell-Badge, a stem cell expert at the National Institute of Medical Research in London, does not think the approach will work. He told the Telegraph newspaper that the 'presence of two X chromosomes is incompatible with this. Moreover they need genes from the Y chromosome [from the male sperm] to go through meiosis. So they are at least double damned'. Safety issues have also been raised, since the mice pups in Nayernia's initial study had health problems.
A Brazilian team of scientists lead by Dr Irina Kerkis at the Butantan Institute in Sao Paolo also claim to have made sperm and eggs from male mouse ESCs, and are currently starting to take the work into human cells. The research brings hope to people dealing with infertility, a problem that affects one in six couples, although scientists say the process is still in its infancy and treatments are a long way off.
There is also potential to use 'induced pluripotent stem cells', stem cells derived from human skin cells, as a starting point for the process. This could enable gay men to donate skin cells that would be used to create stem cells from which eggs could be formed. The eggs could then be fertilised using sperm from his partner, and placed in a surrogate mother.
Greg Aharonian, a patent analyst in the US, is trying to patent the technology behind 'female' sperm and 'male' eggs. A self-proclaimed 'troublemaker', he wants to undermine the argument that marriage should remain heterosexual because its main purpose is procreation.
The controversial developments have provoked mixed responses in the UK and US. Mike Judge from the Christian Institute faith group says that 'children need male and a female role models'. Many religious groups still oppose gay marriage. Josephine Quintavalle, from the pro-life lobby group Comment on Reproductive Ethics, says: 'we are looking at absurd solutions to very obscure situations and not addressing the main issue. Nobody is interested in looking at what is causing infertility - social reasons such as obesity, smoking and age'.

Less Dud, More Stud Sperms

The University of Michigan's sperm sorter consists of a penny-size silicon chip divided into two channels. Semen is dripped onto one side, a saline solution on the other. Where the channels meet, the healthy, or motile, sperm swim over to the saline channel, leaving the dead or slow sperm behind. The healthy sperm are then collected for in vitro fertilization. University of Michigan scientists have developed a new technique to sort out the swimmers from the duds in semen, which could lead to a more efficient way for men who suffer from low sperm counts to make babies.

Current methods use centrifugation, which spins the sperm at very high speed. But the technique isn't efficient because live sperm are pelted with dead ones, causing a significant number of viable sperm to die in the separation. "We can harvest motile sperm from samples where there is a low number without causing any damage to the sperm," said team member Dr. Gary Smith, associate professor of obstetrics and gynecology at the University of Michigan Health System.

In men with healthy sperm counts, each ejaculation contains about 200 million to 400 million sperm. For these men, in vitro fertilization using centrifugal separation is relatively easy because it only takes 10 million to 20 million motile sperm to fertilize an egg in a petri dish. But men with low sperm counts have had less success. "For men with very low sperm count, these other techniques are often unable to recover any motile sperm," said Shuichi Takayama, assistant professor in the Biomedical Engineering program at the University of Michigan, where the new sorter is being developed. Other methods to pinpoint live sperm in a low sperm sample require a microscope and a lot of patience. The new sperm sorter may put an end to this laborious hand sorting. "It may mean that instead of having a well-trained technician, you could have one that is not so well-trained," said Dr. Mark Surrey, of the Southern California Reproductive Center in Beverly Hills.

So far the sorter has fared well in trials. In one test the team used a sample in which only 44 percent of the sperm was motile. After going through the sorter, the count of motile sperm went up to 98 percent. The sorter employs microfluidics, a branch of physics and biotechnology that examines the microscopic flow of fluids. Within the device everything is pushed downstream by gravity and surface tension. The Michigan team notes, however, that more tests are needed before the sorter becomes a mainstay in doctors' offices. Smith said he expects it will be ready for clinical use in one to two years.