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Of Mice Not Men: Controlling fertility; itsy bitsy robot spiders

This is a recurring column on early stage research in animals or other laboratory models that has not entered the clinic yet but could have implications for future research and development of human medicines.

Controlling follicle health and fertility in mice

Two genes related to ovarian follicles may shed light on a cause of female infertility, according to a study published in the journal PLOS Genetics.

About 11% of women in the U.S. have experienced fertility issues, an area of concern in women's health given a reported increase in the average age of mothers, according to the Centers for Disease Control and Prevention. Age affects the health of ovarian follicles, each of which contains an immature egg, or oocyte.

Communication between a follicle's component cells, including the egg cell and surrounding support structures called granulosa cells, are needed for optimum ovarian follicle health. Follicles die if the granulosa cell and oocyte are unable to communicate, but the mechanism through which the cellular communication is established is unknown.

Researchers at the University of Wisconsin-Madison School of Veterinary Medicine had previously found that deleting the two genes Irx3 and Irx5 led to defective follicles and impaired fertility in mice. In a new study, they tried to determine how the genes cooperate to maintain follicle health.

SNL Image

Using mutant mouse models, researchers discovered that at a certain stage of follicle formation, the two genes synchronize granulosa cells with the eggs and help them set up communication networks. The two cell types extend their membranes to form junctions, allowing the two-way transport of signals.

"We think of Irx3 and Irx5 as the supervisors in connecting these two cells," said Joan Jorgensen, a professor in the school's department of comparative biosciences who led the study.

However, Jorgensen said researchers are not yet sure whether the genes affect humans the same way.

"We want to be able to link it to human causes," she said. "If we can figure out how those networks are placed, we think that will be a major step in understanding the basic foundations of how follicles are built. That will go a long way toward helping women that have infertility, especially those that undergo premature ovarian failure."

Blocking hormone to prevent pancreatic cancer

Blocking a hormone associated with obesity may prevent pancreatic cancer caused by a diet high in saturated fats, according to a study in the American Journal of Physiology-Gastrointestinal and Liver Physiology.

Georgetown University researchers conducted experiments on mice to explore the relationships between dietary fat, a digestive hormone called cholecystokinin, or CCK, and pancreatic cancer. CCK has been associated with pancreatic cancer growth, and increased levels of the hormone are related to diets high in fat.

In one study, mice treated with the CCK-blocking drug proglumide experienced less tumor growth even when given a high-fat diet compared to a control group. In another study, dietary fat did not induce cancer growth in mice without CCK receptors on pancreatic cells.

According to the experiments, CCK may stimulate pancreatic cancer growth, and blocking the hormone's receptors could be part of treating and preventing the disease.

"Most patients with advanced pancreatic cancer succumb to the disease due to metastases; therefore a compound that blocks metastases, even when the primary tumor size is large, may have clinical significance," according to the researchers.

Itsy bitsy robotic spider

Researchers created a robotic spider to show off a new technology that could allow animal-like robots to access hard-to-reach areas, according to a study in the journal Advanced Materials.

Small soft robotic systems are usually very simple and with only one possible type of movement. But researchers at Harvard University's Wyss Institute for Biologically Inspired Engineering, Harvard John A. Paulson School of Engineering and Applied Sciences, and Boston University have created a soft robotic spider made only of silicone rubber with 18 degrees of freedom, allowing for changes in structure, motion and color. The researchers call the devices Microfluidic Origami for Reconfigurable Pneumatic/Hydraulic, or MORPH.

Donald Ingber, Wyss Institute founding director, said the technology "could enable an entirely new approach to endoscopy and microsurgery."

Itch switch

A molecule that causes painful skin has been discovered to also trigger itch, according to findings on a study of mice published in the journal JNeurosci.

Two distinct pathways through a molecule called sphingosine 1-phosphate, or S1P, produce each sensation, according to a study led by Diana Bautista of the molecular and cell biology department at the University of California, Berkeley. Blocking a receptor of the molecule may be a potential treatment to manage pain and itch and could be a potential target for analgesics and antipruritics.

Potential new drugs for heart disease

Researchers at Cleveland Clinic were able to reverse two major risk factors for heart disease in a study on mice through a single dose of a new drug.

The potential new class of drugs targets a specific pathway to prevent gut microbes from producing a harmful molecule associated with heart disease, according to the study published in Nature Medicine. The medicine lowered levels of a gut microbe called trimethylamine N-oxide, or TMAO, reversing diet-induced clumping activity in the blood that can lead to excessive clot formation.

"To our knowledge, this is the most potent therapy to date for 'drugging' the microbiome to alter a disease process," said lead investigator Stanley Hazen. "Gut bacteria are altered but not killed by this drug, and there were no observable toxic side effects."