IVF THE NEXT STEP IN LIVE DONOR UTERUS TRANSPLANT PROJECT

In the spring of 2013, a team of researchers and doctors at the University of Gothenburg performed the last of nine planned uterus transplants. The six-month follow up shows that live-donor uterus transplantation has a low risk despite extended surgery duration. In the next phase of the world-unique research project researchers will help seven of the women become pregnant through IVF treatment.

In Sweden alone, an estimated 2,000 young women of fertile age cannot become pregnant either because they were born without a womb or lost it later due to disease.

Professor Mats Brännström, researcher at the University of Gothenburg and chief physician, is leading a unique research project aiming to make it possible for these women to have a uterus transplant and then get pregnant.

A decade of research 

After more than a decade of research that has been evaluated in almost 40 scientific articles, in May 2012 the research team received permission from the Regional Ethical Review Board in Gothenburg to perform uterus transplants on ten Swedish women -- the first in the world with living donors.

The first transplant was completed 15 September 2012, and the ninth and final in the spring of 2013. The tenth woman involved in the project had to be denied at an early stage for medical reasons. Five of the donors are mothers of the receivers; the remaining four a close relative.

Scientific and medical importance In two of the nine cases, the transplanted uterus had to be removed. In one cases due to blood clots in the transplanted blood vessels, in the other because of a local infection that was not fully treatable with antibiotics.

'In a scientific and medical perspective, the transplants have been successful, especially in comparison with other types of transplants that have been introduced and where far fewer initial operations have been successful.'

'The women who had to have their transplanted wombs removed were of course very disappointed, but both of them have recovered well,' says Professor Brännström.

Next phase

The first transplant patients have now had their new uterus for 16 months. During 2014 the second phase of the research project will continue, and the seven transplant patients' own embryos -- produced via IVF prior to the transplant -- will be placed in their uterus with the aim of starting a pregnancy.

`We have made the first attempts at this, but with respect to the women´s integrity we will not comment on the results in the specific cases´, says Brännström.

'The prospects for success are good. On average, the women started menstruating about two months after the transplant, and we followed up on the women twice a week during the first month after the procedure, then once a week for two months and after that every other week. We found and treated a few mild cases of transplant rejection, but after six months, the immunosuppression could be reduced to relatively low levels in most cases and today all women are doing well and have returned to work,' says Brännström.

International interest 

The project is the world's first systematic and research-based attempt to find a treatment for women with uterine infertility. Several medical, psychological and quality of life-related parameters are monitored among the women, which will be of great help for further progress in the field.

A number of research groups around the world are awaiting the results of the Gothenburg study in order to launch similar observational studies.

The article The first clinical uterus transplantation trial: a six-month report was published in Fertility and Sterility on 28 February. In summary, this study shows that a live-donor UTx procedure has a low risk despite extended surgery duration.

CLUE TO WHY FEMALES LIVE LONGER THAN MALES

A study from the University of Exeter has found that male flies die earlier than their female counterparts when forced to evolve with the pressures of mate competition and juvenile survival. The results could help researchers understand the mechanisms involved in aging.

The research, published in the journal Functional Ecology, used populations of the fly Drosophila simulans that had evolved under different selection regimes. The study shows that mate competition (sexual selection), along with survival (natural selection), is tougher on male aging than it is on females reducing their lifespan by about a third.

Some species, like the flies in this study, age quickly over a number of days while others -- including some trees and whales -- age slowly across centuries.

Professor David Hosken from Biosciences at the University of Exeter said: "We found dramatic differences in the effects of sexual and natural selection on male and female flies. These results could help explain the sex differences in lifespan seen in many species, including humans, and the diverse patterns of aging we observe in nature."

The flies were subjected to elevated or relaxed sexual and natural selection and left to evolve in these conditions. To elevate sexual selection groups of males were housed with single females. A stressful temperature was used to elevate natural selection.

Males court females by singing, dancing and smelling good but their efforts come at considerable cost and this cost is amplified when they also have to cope with stressful temperatures.

The results of the study showed that under relaxed sexual and natural selection, male and female flies had very similar lifespans -- around 35 days. However males that evolved under elevated sexual selection and elevated natural selection had a much shorter lifespan -- just 24 days -- and died seven days earlier than females under the same conditions.

Both sexual selection and natural selection were found to affect lifespan but their effects were greatest on males. The findings show that the sexes can respond differently to the same selection regimes.

TARANTULA VENOM ILLUMINATES ELECTRICAL ACTIVITY IN LIVE CELLS

Researchers at the University of California, Davis, Lawrence Berkeley National Laboratory and Marine Biological Laboratory in Woods Hole, Massachusetts, have created a cellular probe that combines a tarantula toxin with a fluorescent compound to help scientists observe electrical activity in neurons and other cells. The probe binds to a voltage-activated potassium ion channel subtype, lighting up when the channel is turned off and dimming when it is activated.

This is the first time researchers have been able to visually observe these electrical signaling proteins turn on without genetic modification. These visualization tools are prototypes of probes that could some day help researchers better understand the ion channel dysfunctions that lead to epilepsy, cardiac arrhythmias and other conditions. The study appears in the Proceedings of the National Academy of Sciences (PNAS)on October 20.

"Ion channels have been called life's transistors because they act like switches, generating electrical feedback" said senior author Jon Sack, assistant professor of physiology and membrane biology at UC Davis. "To understand how neural systems or the heart works, we need to know which switches are activated. These probes tell us when certain switches turn on."

Voltage-gated channels are proteins that allow specific ions, such as potassium or calcium, to flow in and out of cells. They perform a critical function, generating an electrical current in neurons, muscles and other cells. There are many different types, including more than 40 potassium channels. Though other methods can very precisely measure electrical activity in a cell, it has been difficult to differentiate which specific channels are turning on.

"There are about 40 voltage-gated potassium channel genes that are basically doing the same thing, and it's been shockingly hard to figure out which ones are doing something that's physiologically relevant," Sack said.

The tarantula toxin, guangxitoxin-1E, was an ideal choice because it naturally binds to the Kv2 channels. These channels are expressed in most, if not all, neurons, yet their regulation and activity are complex and actively debated. Sack and his laboratory worked closely with Bruce Cohen, a scientist in the Lawrence Berkeley Lab's Molecular Foundry, who has been studying how fluorescent molecules and nanoparticles can be used to image live cells.s

To study the channels, the team engineered variants of tarantula toxin that could be fluorescently labeled and retain function. These probes were designed to bind to the potassium channels when they were at rest and let go when they became active. The researchers then tested them on living cells. To their surprise, the probes worked right away.

"A lot of times you see ambiguous results, but when we added the probes to living cells there was a very clear signal," Sack said. "When we added potassium to stimulate the cells, the probes fell right off."

While this is just a first step towards imaging the activity of potassium and possibly other ion channels, this approach holds vast potential to help scientists understand the underlying mechanisms behind cardiac arrhythmias, muscle defects and other channelopathies.

"There are dozens of known channelopathies, and more being uncovered at an increasing pace" Sack said. "If you have electrical signaling, you have to have a potassium channel, and when that channel goes bad, the cell doesn't work the same anymore. For example, the Kv2.1 channel that this probe binds to leads to epilepsy when it's not functioning properly."

In addition, the ability to better observe electrical signaling could help researchers map the brain at its most basic levels.

"Understanding the molecular mechanisms of neuronal firing is a fundamental problem in unraveling the complexities of brain function," Cohen said.

While creating a probe that can read whether the Kv2.1 channel is firing or at rest is an important proof-of-concept, there's still a lot of work to be done. Sack and Cohen will continue to collaborate, testing other types of spider venoms that bind to different potassium channels.

"The beauty of this is the potential," Sack said. "This is a toehold into a new way of visualizing electrical activity, and there's a huge family of spider toxins that target different ion channels. We've tagged a Ford, we should be able to tag a Chevy."