Featured Research

from universities, journals, and other organizations

Early menopause: A genetic mouse model of human primary ovarian insufficiency

Date:
August 30, 2012
Source:
Emory University
Summary:
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.

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.

The research in Jin's laboratory was supported by the National Institute of Neurological Disorders and Stroke (NS051630 and NS067461). Chen's laboratory is supported by the Chinese Academy of Sciences, the National Basic Research Program of China and the National Science Foundation of China.


Story Source:

The above story is based on materials provided by Emory University. Note: Materials may be edited for content and length.


Journal Reference:

  1. J. C. K. Lui, O. Nilsson, Y. Chan, C. D. Palmer, A. C. Andrade, J. Hirschhorn, J. Baron. Synthesizing genome-wide association studies and expression microarray reveals novel genes that act in the human growth plate to modulate height. Human Molecular Genetics, 2012; DOI: 10.1093/hmg/dds347

Cite This Page:

Emory University. "Early menopause: A genetic mouse model of human primary ovarian insufficiency." ScienceDaily. ScienceDaily, 30 August 2012. <www.sciencedaily.com/releases/2012/08/120830105430.htm>.
Emory University. (2012, August 30). Early menopause: A genetic mouse model of human primary ovarian insufficiency. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2012/08/120830105430.htm
Emory University. "Early menopause: A genetic mouse model of human primary ovarian insufficiency." ScienceDaily. www.sciencedaily.com/releases/2012/08/120830105430.htm (accessed July 25, 2014).

Share This




More Plants & Animals News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How to Make Single Serving Smoothies: Howdini Hacks

How to Make Single Serving Smoothies: Howdini Hacks

Howdini (July 24, 2014) Smoothies are a great way to get in lots of healthy ingredients, plus they taste great! Howdini has a trick for making the perfect single-size smoothie that will save you time on cleanup too! All you need is a blender and a mason jar. Video provided by Howdini
Powered by NewsLook.com
Boy Attacked by Shark in Florida

Boy Attacked by Shark in Florida

Reuters - US Online Video (July 24, 2014) An 8-year-old boy is bitten in the leg by a shark while vacationing at a Florida beach. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Goma Cheese Brings Whiff of New Hope to DRC

Goma Cheese Brings Whiff of New Hope to DRC

Reuters - Business Video Online (July 24, 2014) The eastern region of the Democratic Republic of Congo, mainly known for conflict and instability, is an unlikely place for the production of fine cheese. But a farm in the village of Masisi, in North Kivu is slowly transforming perceptions of the area. Known simply as Goma cheese, the Congolese version of Dutch gouda has gained popularity through out the region. Ciara Sutton reports. Video provided by Reuters
Powered by NewsLook.com
Tyrannosaur Pack-Hunting Theory Aided By New Footprints

Tyrannosaur Pack-Hunting Theory Aided By New Footprints

Newsy (July 24, 2014) A new study claims a set of prehistoric T-Rex footprints supports the theory that the giant predators hunted in packs instead of alone. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

    Health News

      Environment News

        Technology News



          Save/Print:
          Share:

          Free Subscriptions


          Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

          Get Social & Mobile


          Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

          Have Feedback?


          Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
          Mobile: iPhone Android Web
          Follow: Facebook Twitter Google+
          Subscribe: RSS Feeds Email Newsletters
          Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins