The alien within: Fetal cells influence maternal health during pregnancy (and long after)

Dramatic research has shown that during pregnancy, cells of the fetus often migrate through the placenta, taking up residence in many areas of the mother's body, where their influence may benefit or undermine maternal health.

Credit: Infographic by Jason Drees, Biodesign Institute

Parents go to great lengths to ensure the health and well-being of their developing offspring. The favor, however, may not always be returned.

Dramatic research has shown that during pregnancy, cells of the fetus often migrate through the placenta, taking up residence in many areas of the mother's body, where their influence may benefit or undermine maternal health.

The presence of fetal cells in maternal tissue is known as fetal microchimerism. The term alludes to the chimeras of ancient Greek myth--composite creatures built from different animal parts, like the goat-lion-serpent depicted in an Etruscan bronze sculpture.

According to Amy Boddy, a researcher at Arizona State University's Department of Psychology and lead author of a new study, chimeras exist. Indeed, many humans bear chimerical traits in the form of foreign cells from parents, siblings or offspring, acquired during pregnancy.

"Fetal cells can act as stem cells and develop into epithelial cells, specialized heart cells, liver cells and so forth. This shows that they are very dynamic and play a huge role in the maternal body. They can even migrate to the brain and differentiate into neurons," Boddy says "We are all chimeras."

Fellow ASU researchers Angelo Fortunato, Melissa Wilson Sayres and Athena Aktipis joined Boddy for the new study. Fortunato is with the Biodesign's Institute's Human and Comparative Genomics Lab. Wilson Sayres and Aktipis--both with Biodesign's Center for Evolution and Medicine-- are also researchers with ASU's School of Life Sciences and Department of Psychology, respectively.

Mother's little helpers?

While fetal microchimerism is a common occurrence across placental mammals, (including humans), the effects of such cells on maternal health remain a topic of fierce debate in the biological community.

In research appearing in the advanced online edition of the journal Bioessays, Boddy and her colleagues review the available literature on fetal microchimerism and human health, applying an evolutionary framework to predict when fetal cells are inclined to act cooperatively to enhance maternal health and when their behavior is likely to be competitive, occasionally leading to adverse effects on the mother.

Fetal cells may do more than simply migrate to maternal tissues. The authors suggest they can act as a sort of placenta outside the womb, redirecting essential assets from the maternal body to the developing fetus. Cells derived from the fetus--which can persist in maternal tissues for decades after a child is born--have been associated with both protection and increased susceptibility to a range of afflictions, including cancer and autoimmune diseases like rheumatoid arthritis.

But, as co-author Wilson Sayres, cautions, "it's not only a tug of war between maternal and fetal interests. There is also a mutual desire for the maternal system to survive and provide nutrients and for the fetal system to survive and pass on DNA."

If some degree of fetal microchimerism exerts a beneficial effect on maternal and offspring survival, it will likely be selected for by evolution as an adaptive strategy.

A review of existing data on fetal microchimerism and health suggests that fetal cells enter a cooperative relationship in some maternal tissues, compete for resources in other tissues and may exist as neutral entities--hitchhikers simply along for the ride. It is likely that fetal cells play each of these roles at various times.

For example, fetal cells may contribute to inflammatory responses and autoimmunity in the mother, when they are recognized as foreign entities by the maternal immune system. This may account in part for higher rates of autoimmunity in women. (For example, women have three times higher rates of rheumatoid arthritis, compared with men.)

Fetal cells can also provide benefits to mothers, migrating to damaged tissue and repairing it. Their presence in wounds--including caesarian incisions--points to their active participation in healing. In other cases, fetal cells from the placenta are swept through the bloodstream into areas including the lung, where they may persist merely as bystanders.

Parental discretion advised

Applying a cooperation and conflict approach, the authors make testable predictions about the circumstances favoring fetal cell cooperation or competition and attendant positive or negative effects on maternal health.

"Cooperation theory and evolutionary analyses are powerful tools for helping us to unravel the complex effects of fetal cells on the maternal body. They can help us to predict when fetal cells are likely to contribute to maternal health and when they may be manipulating maternal tissues for the benefit of the offspring and potentially contributing to maternal disease in the process," says Aktipis.

Evolutionary theory suggests that fetal cells will act cooperatively to enhance maternal health where the economic cost of doing so is low, for example, in tissue maintenance. Where the cost to fetal cells is high, including the division of limited resources between fetus and mother, competition is the more likely outcome, with escalating conflict leading to harmful effects for mother, developing fetus or both.

Fetal cells appear to play a complex role in the female breast and have been detected in over half of all women sampled. Given the co-evolution of maternal and fetal cells over the 160 million year course of placental mammalian evolution, it appears likely that fetal cells are active participants in breast development and lactation.

Milk production is a vital but energy-intensive activity for the mother, requiring subtle regulation. Poor lactation--a common affliction--may be linked with low fetal cell count in breast tissue. (The hypothesis suggests that a simple, non-invasive test for fetal cell abundance in breast milk could provide the first conclusive evidence of fetal cell influence on maternal health.)

With respect to breast cancer, existing data paints a complex picture. Fetal cells are generally found in lower abundance in women with breast cancer, compared with healthy women, suggesting they may play a protective role. On the other hand, some data indicates that fetal cells may be linked with a transient increase in the risk of breast cancer in the years immediately following pregnancy.

The thyroid gland performs a broad range of regulatory functions and during pregnancy, is involved in the efficient transfer of heat from the mother to the offspring. Again, fetal cells found in the thyroid are implicated and may be manipulating thyroid activity to enhance heat transfer to the fetus, potentially at the energetic expense of the mother.

Fetal cells occur more frequently in both the blood and thyroid tissue of women with thyroid diseases including Hashimoto's thyroiditis, Graves' disease and thyroid cancer, compared with healthy women. (Intriguingly, cancer of the thyroid is the only non-sex-specific form of cancer found more frequently in women than men.) The authors suggest that the maternal system, in attempting to wrest control from fetal cell influence, may induce hazardous levels of autoimmunity and inflammation.

Fetal attraction

The current overview represents a tentative step toward untangling the myriad influences of fetal microchimerism on human health. One of the more tantalizing possibilities raised in the new study is that fetal cells may be commandeering neural pathways overseeing emotion and behavior. They may, for example, hijack mechanisms triggering the release of oxytocin, a hormone long associated with the emotional bonding of mother and infant.

Indeed, fetal cells could be suspects in a broad range of physical and emotional manifestations in the mother, including pregnancy-related afflictions like morning sickness or postpartum depression. Even early onset menopause could be the result of fetal cell efforts to remove the mother from further child-bearing, in order to secure maximum resources for the fetus and eventually, the growing child.

Finally, the authors note, fetal microchimerism may be one piece of a subtle and dizzyingly complex puzzle. Cell traffic is actually bi-directional, with the fetus receiving cells from the mother. Fetal cells from maternal tissue may cross the placental barrier during subsequent pregnancies, potentially influencing the health of later offspring. To further complicate matters, cells from later fetuses can also cross the placenta to enter the microchimeric arena, perhaps introducing sibling rivalries for the mother's limited resources.

Fetal cells may eventually provide a novel and powerful means of diagnosing existing conditions and predicting long-term maternal health. As the authors note, they could also be applied therapeutically in the future, potentially for the treatment of poor lactation, for wound healing, tumor reduction and perhaps even pregnancy-linked psychological disorders.

Identification of fetal cells in maternal gut, liver or brain tissues is only a first step.

To tease out the true function of these cells, researchers need to examine their gene expression and interaction with maternal tissues. Inspection of maternal cells in surrounding tissue will help determine if they are immune cells targeting fetal cell interlopers or normal epithelial cells, existing in harmony.

"If future research bears out the predictions of this framework, it could transform the way we approach, treat and prevent a variety of diseases that affect women, especially new mothers," says Aktipis.

Improved methods of screening will help scientists listen in on the intricate dialogue between fetal and maternal cells, deepening our understanding of maternal health and disease.

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Story Source:

The above post is reprinted from materials provided by Arizona State University. The original item was written by Richard Harth. Note: Materials may be edited for content and length.

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Journal Reference:

1. Amy M. Boddy, Angelo Fortunato, Melissa Wilson Sayres, Athena Aktipis.Fetal microchimerism and maternal health: A review and evolutionary analysis of cooperation and conflict beyond the womb. BioEssays, 2015; DOI: 10.1002/bies.201500059

When a 'UFO' flies by, does it bother bears?

On a completely autonomous mission, the UAV flies towards the location of a collared bear in northwestern Minnesota

If an unidentified flying object suddenly appeared in the sky, it's likely your heart would beat faster. Now, researchers reporting in the Cell Press journalCurrent Biology on August 13 have found that the same is true for bears.

The UFOs in this case are actually unmanned aerial vehicles (UAVs), which have become increasingly valuable to wildlife researchers, allowing them to observe animals, including endangered species, in their natural settings from long distances and over difficult terrain. It had appeared as though the animals were taking these encounters in stride. For instance, American black bears rarely seem to startle or run away when a UAV comes near. But the new study reveals that despite the bears' calm demeanor when in the presence of UAVs, their heart rates soar, a sign of acute stress.

"Some of the spikes in the heart rate of the bears were far beyond what we expected," says Mark Ditmer of the University of Minnesota, St. Paul. "We had one bear increase her heart rate by approximately 400 percent--from 41 beats per minute to 162 beats per minute. Keep in mind this was the strongest response we saw, but it was shocking nonetheless."

The researchers fitted free-roaming American black bears living in northwestern Minnesota with Iridium satellite GPS collars and cardiac biologgers. The collars sent the researchers an email with each bear's location every 2 minutes while the biologgers captured every heartbeat. Then Ditmer and his colleagues programmed a UAV to fly to the bear's most recent location.

In the end, the researchers were able to analyze their data very precisely to find out what hidden effect their UAV flights--which lasted only a brief 5 minutes due to battery life and other logistical constraints--might have had on the bears.

In 18 UAV flights taken in the vicinity of four different bears, individuals only twice showed any major change in their behavior in response to the UAVs. However, the biologgers revealed consistently strong physiological responses. All of the bears in the study responded to UAV flights with elevated heart rates. Fortunately, the bears recovered very quickly.

"Without the use of the biologger, we would have concluded that bears only occasionally respond to UAVs," Ditmer says.

The researchers say it will now be important to consider the additional stress on wildlife from UAV flights when developing regulations and best scientific practices. UAVs are growing in popularity for many uses in addition to research--for example, to discourage poachers and track down wildlife for ecotourists. In many countries, few rules are in place to guide UAV use.

"UAVs hold tremendous potential for scientific research and as tools for conservation," Ditmer says. "However, until we know which species are tolerant of UAVs, at what distance animals react to the presence of UAVs, and whether or not individuals can habituate to their presence, we need to exercise caution when using them around wildlife."

Ditmer and his colleagues are now working with captive bears to find out whether the animals can get used to overhead UAV flights over time and, if so, how long it takes.

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Story Source:

The above post is reprinted from materials provided by Cell Press. Note: Materials may be edited for content and length.

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Journal Reference:

1. Ditmer et al. Bears Show a Physiological but Limited Behavioral Response to Unmanned Aerial Vehicles. Current Biology, August 2015 DOI: 10.1016/j.cub.2015.07.024

Microscopic rake doubles efficiency of low-cost solar cells

A scanning electron microscope image shows the rigid pillar-like bristles of the FLUENCE rake, which is used to apply light-harvesting polymers to a solar cell. The distance between the pillars is 1 micrometer, about one-hundredth the diameter of a human hair.

Researchers from the Department of Energy's SLAC National Accelerator Laboratory and Stanford University have developed a manufacturing technique that could double the electricity output of inexpensive solar cells by using a microscopic rake when applying light-harvesting polymers.

When commercialized, this advance could help make polymer solar cells an economically attractive alternative to those made with much more expensive silicon-crystal wafers.

In experiments, solar cells made with the tiny rake double the efficiency of cells made without it and are 18 percent better than cells made using a microscopic straightedge blade.

The research was led by Zhenen Bao, a chemical engineering professor at Stanford and a member of the Stanford Institute for Materials and Energy Sciences (SIMES), which is run jointly by SLAC and Stanford. The team reported its results August 12 in Nature Communications.

"The fundamental scientific insights that come out of this work will give manufacturers a rational approach to improving their processes, rather than relying simply on trial and error," Bao said.

"We also expect this simple, effective and versatile concept will be broadly applicable to making other polymer devices where properly aligning the molecules is important."

The Problem With Polymers

Although prices for silicon-based solar cells are dropping, it still takes five to 15 years before they produce enough electricity to offset their purchase and installation. Silicon solar cells also require a large amount of energy to manufacture, which partly offsets their value as renewable energy sources.

Polymer-based photovoltaic cells are much cheaper because they're made of inexpensive materials that can be simply painted or printed in place. They are also flexible and require little energy to manufacture. While small, lab-scale samples can convert more than 10 percent of sunlight into electricity, the large-area coated cells have very low efficiency -- typically converting less than 5 percent, compared with 20-25 percent for commercial silicon-based cells.

Polymer cells typically combine two types of polymers: A donor, which converts sunlight into electrons, and an acceptor, which stores the electrons until they can be removed from the cell as usable electricity. But when this mixture is deposited on a cell's conducting surface during manufacturing, the two types tend to separate as they dry into an irregular assortment of large clumps, making it more difficult for the cell to produce and harvest electrons.

The SLAC/Stanford researchers' solution is a manufacturing technique called "fluid-enhanced crystal engineering," or FLUENCE, which was originally developed to improve the electrical conduction of organic semiconductors.

In the current work, as the polymers are painted onto a conducting surface, they are forced through a slightly angled rake containing several rows of stiff microscopic pillars. The rake is scraped along the surface at the relatively slow speed of 25-100 micrometers per second, which translates to 3.5-14.2 inches per hour. The large polymer molecules untangle and mix with each other as they bounce off and flow past the pillars, ultimately drying into tiny nanometer-sized crystals of uniform size with enhanced electrical properties.

Simulations and X-rays

The researchers used computer simulations and X-ray analyses at two DOE Office of Science User Facilities -- SLAC's Stanford Synchrotron Radiation Lightsource (SSRL) and Lawrence Berkeley National Laboratory's Advanced Light Source (ALS) -- to customize the FLUENCE rake for making solar cells.

"At SSRL, the team used X-ray diffraction to measure the degree to which the polymers formed crystals and X-ray scattering to determine how clearly the two polymers segregated themselves," said Mike Toney, SSRL Materials Sciences group leader and a co-author on the paper. "These are bread-and-butter techniques for which we've developed some novel approaches at SSRL in recent years."

To achieve the polymer patterns they wanted for the solar cells, the researchers made the pillars in the rake much shorter and more densely packed than those used earlier for organic semiconductors. They were 1.5 micrometers high and 1.2 micrometers apart; for comparison, a human hair is about 100 micrometers in diameter.

Close, But Not Too Close

"Ideally, the two types of photovoltaic polymers should be close enough to each other for electrons to move quickly from donor to acceptor, but not so close that the acceptor gives back its electrons before they can be harvested to electricity," said Yan Zhou, a Stanford researcher on Bao's team.

"Our new FLUENCE rake achieves this happy medium. Because we understand what's happening, we can tune the rake design and processing speed to alter the final polymer structures."

Future research will be aimed at applying the FLUENCE technique to other polymer blends and adapting it to rapid industrial-scale roll-to-roll printing processes -- which can reach speeds of 50 miles per hour -- that promise the lowest solar-cell manufacturing costs.

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Story Source:

The above post is reprinted from materials provided by SLAC National Accelerator Laboratory. Note: Materials may be edited for content and length.

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Journal Reference:

1. Ying Diao, Yan Zhou, Tadanori Kurosawa, Leo Shaw, Cheng Wang, Steve Park, Yikun Guo, Julia A. Reinspach, Kevin Gu, Xiaodan Gu, Benjamin C. K. Tee, Changhyun Pang, Hongping Yan, Dahui Zhao, Michael F. Toney, Stefan C. B. Mannsfeld, Zhenan Bao. Flow-enhanced solution printing of all-polymer solar cells. Nature Communications, 2015; 6: 7955 DOI: 10.1038/ncomms8955

Mini X-ray source with laser light

The world’s first image of a fly taken with the help of an all-laser-based X-ray tomography imaging method. It consists of around 1500 individual images. Even extremely fine structures appear in three-dimensional detail. These would remain invisible in a conventional X-ray image.

Physicists from Ludwig-Maximilians-Universität, the Max Planck Institute of Quantum Optics and the TU München have developed a method using laser-generated X-rays and phase-contrast X-ray tomography to produce three-dimensional images of soft tissue structures in organisms.

With laser light, physicists in Munich have built a miniature X-ray source. In so doing, the researchers from the Laboratory of Attosecond Physics of the Max Planck Institute of Quantum Optics and the Technische Universität München (TUM) captured three-dimensional images of ultrafine structures in the body of a living organism for the first time with the help of laser-generated X-rays. Using light-generated radiation combined with phase-contrast X-ray tomography, the scientists visualized ultrafine details of a fly measuring just a few millimeters. Until now, such radiation could only be produced in expensive ring accelerators measuring several kilometers in diameter. By contrast, the laser-driven system in combination with phase-contrast X-ray tomography only requires a university laboratory to view soft tissues. The new imaging method could make future medical applications more cost-effective and space-efficient than is possible with today's technologies.

When the physicists Prof. Stefan Karsch and Prof. Franz Pfeiffer illuminate a tiny fly with X-rays, the resulting image captures even the finest hairs on the wings of the insect. The experiment is a pioneering achievement. For the first time, scientists coupled their technique for generating X-rays from laser pulses with phase-contrast X-ray tomography to visualize tissues in organisms. The result is a three-dimensional view of the insect in unprecedented detail.

The X-rays required were generated by electrons that were accelerated to nearly the speed of light over a distance of approximately one centimeter by laser pulses lasting around 25 femtoseconds. A femtosecond is one millionth of a billionth of a second. The laser pulses have a power of approximately 80 terawatts (80 x 1012 watts). By way of comparison: an atomic power plant generates 1,500 megawatts (1.5 x 109 Watt).

First, the laser pulse ploughs through a plasma consisting of positively charged atomic cores and their electrons like a ship through water, producing a wake of oscillating electrons. This electron wave creates a trailing wave-shaped electric field structure on which the electrons surf and by which they are accelerated in the process. The particles then start to vibrate, emitting X-rays. Each light pulse generates an X-ray pulse. The X-rays generated have special properties: They have a wavelength of approximately 0.1 nanometers, which corresponds to a duration of only about five femtoseconds, and are spatially coherent, i.e. they appear to come from a point source.

For the first time, the researchers combined their laser-driven X-rays with a phase-contrast imaging method developed by a team headed by Prof. Franz Pfeiffer of the TUM. Instead of the usual absorption of radiation, they used X-ray refraction to accurately image the shapes of objects, including soft tissues. For this to work, the spatial coherence mentioned above is essential.

This laser-based imaging technique enables the researchers to view structures around one tenth to one hundredth the diameter of a human hair. Another advantage is the ability to create three-dimensional images of objects. After each X-ray pulse, meaning after each frame, the specimen is rotated slightly. For example, about 1,500 individual images were taken of the fly, which were then assembled to form a 3D data set.

Due to the shortness of the X-ray pulses, this technique may be used in future to freeze ultrafast processes on the femtosecond time scale e.g. in molecules -- as if they were illuminated by a femtosecond flashbulb.

The technology is particularly interesting for medical applications, as it is able to distinguish between differences in tissue density. Cancer tissue, for example, is less dense than healthy tissue. The method therefore opens up the prospect of detecting tumors that are less than one millimeter in diameter in an early stage of growth before they spread through the body and exert their lethal effect. For this purpose, however, researchers must shorten the wavelength of the X-rays even further in order to penetrate thicker tissue layers.

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Story Source:

The above post is reprinted from materials provided by Max Planck Institute of Quantum Optics. The original item was written by Thorsten Naeser.Note: Materials may be edited for content and length.

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Journal Reference:

1. J. Wenz, S. Schleede, K. Khrennikov, M. Bech, P. Thibault, M. Heigoldt, F. Pfeiffer, S. Karsch. Quantitative X-ray phase-contrast microtomography from a compact laser-driven betatron source.Nature Communications, 2015; 6: 7568 DOI: 10.1038/ncomms8568