Cellular communication system in mice helps control female fertility

August 2, 2018 by Tyler Fox, University of Wisconsin-Madison
Credit: CC0 Public Domain

When Joan Jorgensen was an undergraduate at the University of Wisconsin-Madison, her roommate confided that she had just one period before going through menopause in high school. Doctors told Jorgensen's roommate that she would never have biological children.

"This is devastating news at any age, let alone a girl," says Jorgensen, who is now a professor in the Department of Comparative Biosciences at the UW-Madison School of Veterinary Medicine.

That experience stuck with Jorgensen, whose research focuses on fertility problems like premature ovarian failure, which leads to an early loss of viable eggs and which her roommate experienced. Using animal models, Jorgensen tries to understand how female fertility is affected by development of the ovary, which includes how cells organize to support eggs for the entire lifetime of that individual.

In new research published Aug. 2 in the journal PLOS Genetics, Jorgensen, graduate researcher Anqi Fu and others discovered that two work together to construct a cellular communication system in the ovaries of mice to maintain healthy eggs. The researchers describe this system as a series of junctions between the eggs and the cells that surround and support the eggs, known as granulosa cells. Both cells reach out to form multiple junctions that exchange information and ensure the proper development and survival of the egg leading up to ovulation.

This research provides a piece of the puzzle of female infertility, and Jorgensen looks to build off these findings to uncover more information on premature ovarian failure and other . Jorgensen and Fu collaborated with researchers at the University of Melbourne, Monash University, and the University of Toronto to complete this work.

Premature ovarian failure, in which the ovaries stop producing estrogen, is often caused by premature loss of the egg supply and affects as many as 3 percent of all women, according to the National Institutes of Health. In most cases the cause is unknown. Problems with the development of follicles—the combination of an egg and its surrounding granulosa cells—are likely behind many cases of premature ovarian failure.

Jorgensen's lab had previously found that mice missing two genes, IRX3 and IRX5, had defective follicles. In the current study, they looked for how these genes work together to keep follicles healthy.

The researchers showed that mice with either IRX3 or IRX5 deleted had fewer pups, which led the researchers to suspect that communication within the follicle was breaking down. Looking within the ovary, they tracked the expression of each gene.

Early on, the researchers saw that IRX3 and IRX5 were expressed throughout the follicle. But as the follicle began to mature, IRX3 became isolated to the egg, while IRX5 was only expressed in the granulosa cells.

From their separate vantage points, these two genes synchronize the two cell types to help them establish communication networks. Jorgensen's team saw that the granulosa cells and the extend parts of their membranes to form junctions with each other. These junctions allow signals to be transported in both directions. With IRX3 or IRX5 deleted, these junctions fell apart, interrupting communication within the follicle and destabilizing it.

"We think of IRX3 and IRX5 as the supervisors in connecting these two ," says Jorgensen.

Despite this discovery of a role for these genes in follicle development in mice, researchers still aren't sure if these same genes have a similar effect in humans.

"That's another thing we would like to learn—we want to be able to link it to human causes," says Jorgensen.

Jorgensen and Fu say the next step will be to evaluate exactly how these genes direct these key cell-to-cell interactions.

"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," says Jorgensen. "That will go a long way towards helping women that have infertility, especially those that undergo premature ovarian failure."

Explore further: Study prompts rethink of how ovaries develop

Related Stories

Study prompts rethink of how ovaries develop

February 8, 2013
(Medical Xpress)—New research from the University of Adelaide will rewrite the text books on how an ovary is formed, as well as providing new insights into women's health and fertility.

Study solves ovarian cell mystery, shedding new light on reproductive disorders

May 6, 2015
Scientists at the National Institutes of Health have solved a long-standing mystery about the origin of one of the cell types that make up the ovary. The team also discovered how ovarian cells share information during development ...

Source of tumor growth in aggressive prostate cancer found

June 17, 2013
Researchers have discovered a molecular switch that explains, at least in part, how some fast-growing prostate cancers become resistant to hormone treatment, a new study conducted in human cell cultures and mice finds. The ...

Recommended for you

Scientists identify method to study resilience to pain

December 14, 2018
Scientists at the Yale School of Medicine and Veterans Affairs Connecticut Healthcare System have successfully demonstrated that it is possible to pinpoint genes that contribute to inter-individual differences in pain.

CRISPR joins battle of the bulge, fights obesity without edits to genome

December 13, 2018
A weighty new study shows that CRISPR therapies can cut fat without cutting DNA. In a paper published Dec. 13, 2018, in the journal Science, UC San Francisco researchers describe how a modified version of CRISPR was used ...

Noncoding mutations contribute to autism risk

December 13, 2018
A whole-genome sequencing study of nearly 2,000 families has implicated mutations in 'promoter regions' of the genome—regions that precede the start of a gene—in autism. The study, which appears in the December 14 issue ...

New method for studying ALS more effectively

December 13, 2018
The neurodegenerative disease ALS causes motor neuron death and paralysis. However, long before the cells die, they lose contact with muscles as their axons atrophy. Researchers at Karolinska Institutet in Sweden have now ...

Paternal grandfather's high access to food may indicate higher mortality risk in grandsons

December 12, 2018
A paternal grandfather's access to food during his childhood is associated with mortality risk, especially cancer mortality, in his grandson, shows a large three-generational study from Stockholm University. The reason might ...

New genetic study could lead to better treatment of severe asthma

December 12, 2018
The largest-ever genetic study of people with moderate-to-severe asthma has revealed new insights into the underlying causes of the disease which could help improve its diagnosis and treatment.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.