Navigation Links
Early menopause: A genetic mouse model of human primary ovarian insufficiency
Date:8/30/2012

Scientists have established a genetic mouse model for primary ovarian insufficiency (POI), a human condition in which women experience irregular menstrual cycles and reduced fertility, and early exposure to estrogen deficiency.

POI affects approximately one in a hundred women. In most cases of primary ovarian insufficiency, the cause is mysterious, although genetics is known to play a causative role. There are no treatments designed to help preserve fertility. Some women with POI retain some ovarian function and a fraction (5-10 percent) have children after receiving the diagnosis.

Having a mouse model could accelerate research on the causes and mechanisms of POI, and could eventually lead to treatments, says Peng Jin, PhD, associate professor of human genetics at Emory University School of Medicine.

The results were published online recently in the journal Human Molecular Genetics.

The paper was the result of a collaboration between researchers at Emory and the Institute of Zoology, Chinese Academy of Sciences in Beijing. Dahua Chen, PhD, associate director of the State Key Laboratory of Reproductive Biology, is the senior author and postdoctoral fellow Cuiling Lu is the first author. Stephanie Sherman, PhD, professor of human genetics at Emory, is a co-author.

The mouse model builds on research on women who are carriers of a "premutation" for fragile X syndrome, a leading cause of inherited intellectual disability.

The mice have a fragment of a human X chromosome from a fragile X premutation carrier. Other non-genetic mouse models used to study menopause include surgical removal of the ovaries, or exposure of mice to a chemical, 4-vinylcyclohexene diepoxide, which depletes the ovaries.

"While the fragile X premutation is a leading cause of POI, I think this model will be useful and relevant for all women with this condition," Jin says.

Women with the fragile X premutation account for around two percent of spontaneous POI cases and 14 percent of familial POI cases. About 20 percent of women who carry the fragile X premutation experience POI, the disorder now called fragile X-associated POI, or FXPOI.

Fragile X syndrome is caused by the expansion of a "triplet repeat" in a gene (FMR1) that is important for signaling in the brain. In fragile X syndrome, the triplet repeat -- three DNA letters (CGG) repeated many times -- forces the gene to shut off.

For a woman who carries the premutation, the triplet repeat is not large enough to shut the gene off. There is a risk that it will expand in her children enough to generate fragile X syndrome. In addition, the triplet repeat appears to have an effect on the woman's ovaries, independently from its influence on the FMR1 gene.

Jin says studying mice that have an analogous genetic alteration will help scientists understand what's happening to the ovaries in POI. It appears that the RNA coming from the premutation impairs development of the ovarian follicles, the structures in which eggs/oocytes mature.

The research team found that a quarter of premutation-carrying female mice are infertile. When they are housed with male mice, those that do have pups have them a month later on average (12.5 weeks of age compared to 8.5 weeks), and they have fewer pups.

Puberty occurs at roughly five weeks of age in mice, and the premutation mice have alterations in their ovaries already before puberty. At 25 days of age, there are a reduced number of mature follicles in ovaries of the female mice carrying the premutation. Those mice also have altered levels of hormones resembling those of women with POI, such as elevated FSH (follicle stimulating hormone).

The research team found that in the ovaries of mice with the fragile X premutation, ovulation-related genes are less active. In addition, two cellular signaling pathways (Akt/mTOR) are less active in the ovaries, suggesting that drugs that affect those pathways could be used to treat POI.


'/>"/>

Contact: Quinn Eastman
qeastma@emory.edu
404-727-7829
Emory University
Source:Eurekalert

Related biology news :

1. Artificial womb unlocks secrets of early embryo development
2. Mid-Atlantic suburbs can expect an early spring thanks to the heat of the big city
3. An early spring drives butterfly population declines
4. Hazy shades of life on early Earth
5. American Society of Plant Biologists honors early career women scientists
6. Early warning system for seizures could cut false alarms
7. A new gene thought to be the cause in early-onset forms of Alzheimers disease
8. Promising developments in early diagnosis and treatment of mesothelioma
9. Early detection techniques offer hope for improved outcomes in lung cancer patients
10. New study links air pollution and early death in the UK
11. Attendees Save Up To $800 on Boston-area Pharmaceutical and Healthcare Conferences, Early Bird Discounts Expiring April 27
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/19/2017)... ALBANY, New York , April 19, 2017 /PRNewswire/ ... highly competitive, as its vendor landscape is marked by ... in the market is however held by five major ... and Safran. Together these companies accounted for nearly 61% ... majority of the leading companies in the global military ...
(Date:4/11/2017)... GARDENS, Fla. , April 11, 2017 /PRNewswire/ ... management and secure authentication solutions, today announced that ... by Intelligence Advanced Research Projects Activity (IARPA) to ... IARPA,s Thor program. "Innovation has been ... and IARPA,s Thor program will allow us to ...
(Date:4/5/2017)... , April 5, 2017  The Allen Institute for ... Cell Explorer: a one-of-a-kind portal and dynamic digital window ... imaging data, the first application of deep learning to ... stem cell lines and a growing suite of powerful ... for these and future publicly available resources created and ...
Breaking Biology News(10 mins):
(Date:7/20/2017)... ... July 20, 2017 , ... Dr. Asher Kimchi, Founder and ... of the 2017 IAC Awards at the 22nd World Congress on Heart Disease held ... four faculty to receive the Distinguished Fellowship Awards. , Dr. Asher Kimchi, together with ...
(Date:7/20/2017)... ... July 20, 2017 , ... VIC Technology Venture Development™ ... board of directors. This addition continues to strengthen and diversify VIC’s board. , ... and Chairman. “He is a highly accomplished business executive with a broad range of ...
(Date:7/20/2017)... DENVER and PLYMOUTH, Minn., July 20, 2017 ... LLC , a personalized genetic evaluations company, today ... under their partnership investigating a genetic mutation implicated ... to extend the partnership for a second case ... Last year, the KCNQ2 Cure Alliance and Pairnomix ...
(Date:7/20/2017)... (PRWEB) , ... July 20, 2017 , ... ... solution to make clinical trial sites and study participants truly unified. TrialKit, a ... compliant (FDA 21 CFR Part 11) research studies entirely on mobile devices. With ...
Breaking Biology Technology: