Satellite Banner
Genomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

A Molecular Explanation for Age-Related Fertility Decline in Women

Published: Tuesday, July 09, 2013
Last Updated: Tuesday, July 09, 2013
Bookmark and Share
NIH-funded scientists find DNA repair systems, including BRCA1, become less efficient.

Scientists supported by the National Institutes of Health have a new theory as to why a woman’s fertility declines after her mid-30s. They also suggest an approach that might help slow the process, enhancing and prolonging fertility.

They found that, as women age, their egg cells become riddled with DNA damage and die off because their DNA repair systems wear out. Defects in one of the DNA repair genes - BRCA1 - have long been linked with breast cancer, and now also appear to cause early menopause.

“We all know that a woman’s fertility declines in her 40s. This study provides a molecular explanation for why that happens,” said Dr. Susan Taymans, Ph.D., of the Fertility and Infertility Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the NIH institute that funded the study. “Eventually, such insights might help us find ways to improve and extend a woman’s reproductive life.”

The findings appear in Science Translational Medicine.

In general, a woman’s ability to conceive and maintain a pregnancy is linked to the number and health of her egg cells. Before a baby girl is born, her ovaries contain her lifetime supply of egg cells (known as primordial follicle oocytes) until they are more mature.

As she enters her late 30s, the number of oocytes-and fertility-dips precipitously. By the time she reaches her early 50s, her original ovarian supply of about 1 million cells drops virtually to zero.

Only a small proportion of oocytes - about 500 - are released via ovulation during the woman’s reproductive life. The remaining 99.9 percent are eliminated by the woman’s body, primarily through cellular suicide, a normal process that prevents the spread or inheritance of damaged cells.

The scientists suspect that most aging oocytes self-destruct because they have accumulated a dangerous type of DNA damage called double-stranded breaks.

According to the study, older oocytes have more of this sort of damage than do younger ones. The researchers also found that older oocytes are less able to fix DNA breaks due to their dwindling supply of repair molecules.

Examining oocytes from mice, and from women 24 to 41 years old, the researchers found that the activity of four DNA repair genes (BRCA1, MRE11, Rad51 and ATM) declined with age.

When the research team experimentally turned off these genes in mouse oocytes, the cells had more DNA breaks and higher death rates than did oocytes with properly working repair systems.

The research team’s findings stemmed from their initial focus on BRCA1, a DNA repair gene that has been closely studied for nearly 20 years because defective versions of it dramatically increase a woman’s risk of breast cancer.

Using mice bred to lack the BRCA1 gene, the NICHD-supported scientists confirmed that a healthy version of BRCA1 is vital to reproductive health.

BRCA1-deficient mice were less fertile, had fewer oocytes, and had more double-stranded DNA breaks in their remaining oocytes than did normal mice.

Abnormal BRCA1 appears to cause the same problems in humans-the team’s studies suggest that if a woman’s oocytes contain mutant versions of BRCA1, she will exhaust her ovarian supply sooner than women whose oocytes carry the healthy version of BRCA1.

Together, these findings show that the ability of oocytes to repair double-stranded DNA breaks is closely linked with ovarian aging and, by extension, a woman’s fertility. This molecular-level understanding points to new reproductive therapies.

Specifically, the scientists suggest that finding ways to bolster DNA repair systems in the ovaries might lead to treatments that can improve or prolong fertility.

Senior author Kutluk Oktay, M.D., of New York Medical College (NYMC), in Rye and Valhalla, collaborated with colleagues at NYMC and researchers at Istanbul Bilim University, Turkey; Memorial Sloan-Kettering Cancer Center and Weill Medical College of Cornell University, New York; and Yeshiva University, New York.

The work was supported by grants HD53112 and HD61259.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Study Shows Promise of Precision Medicine for Most Common Type of Lymphoma
The study appeared online July 20, 2015, in Nature Medicine.
Tuesday, July 21, 2015
NIH Study Identifies Gene Variant Linked to Compulsive Drinking
Mice carrying the Met68BDNF gene variant would consume excessive amounts of alcohol.
Tuesday, July 21, 2015
In Blinding Eye Disease, Trash-Collecting Cells Go Awry, Accelerate Damage
NIH research points to microglia as potential therapeutic target in retinitis pigmentosa.
Friday, July 03, 2015
Potential Therapeutic for Blinding Eye Disease
NIH research points to microglia as potential therapeutic target in retinitis pigmentosa.
Thursday, July 02, 2015
NCI-MATCH Trial will Link Targeted Cancer Drugs to Gene Abnormalities
Precision medicine trial will open to patient enrollment in July.
Tuesday, June 09, 2015
A New Role for Zebrafish: Larger Scale Gene Function Studies
A relatively new method of targeting specific DNA sequences in zebrafish could dramatically accelerate the discovery of gene function and the identification of disease genes in humans.
Monday, June 08, 2015
NIH Researchers Pilot Predictive Medicine by Studying Healthy People’s DNA
New study sequence the genomes of healthy participants to find “putative,” or presumed, mutations.
Friday, June 05, 2015
Linking Targeted Cancer Drugs to Gene Abnormalities
Investigators at the NIH have announced a series of clinical trials that will study drugs or drug combinations that target specific genetic mutations.
Wednesday, June 03, 2015
Scientists Create Mice with a Major Genetic Cause of ALS and FTD
NIH-funded study provides new platform for testing treatments for several neurodegenerative disorders.
Friday, May 22, 2015
Mice With a Major Genetic Cause of ALS and FTD Created
NIH-funded study provides new platform for testing treatments for several neurodegenerative disorders.
Thursday, May 21, 2015
New Insights into How DNA Differences Influence Gene Activity, Disease Susceptibility
NIH-funded pilot study provides a new resource about variants across the human genome.
Friday, May 08, 2015
Souped-up Remote Control Switches Behaviors On-and-Off in Mice
BRAIN Initiative yields chemical-genetic tool with push-pull capabilities.
Thursday, May 07, 2015
NIH-funded Study Points Way Forward for Retinal Disease Gene Therapy
Benefits for Leber congenital amaurosis peak after one to three years, then diminish.
Tuesday, May 05, 2015
Possible Treatment for Lethal Pediatric Brain Cancer
NIH-funded preclinical study suggests epigenetic drugs may be used to treat leading cause of pediatric brain cancer death.
Tuesday, May 05, 2015
Statement on NIH Funding of Research Using Gene-Editing Technologies in Human Embryos
Researchers modify the gene responsible for a potentially fatal blood disorder using CRISPR/Cas9 technology.
Saturday, May 02, 2015
Scientific News
Long Telomeres Associated with Increased Lung Cancer Risk
Genetic predisposition for long telomeres predicts increased lung adenocarcinoma risk.
Expanding the Brain
A team of researchers has identified more than 40 new “imprinted” genes, in which either the maternal or paternal copy of a gene is expressed while the other is silenced.
Identifying a Key Growth Factor in Cell Proliferation
Researchers discover that aspartate is a limiter of cell proliferation.
Study Uncovers Target for Preventing Huntington’s Disease
Scientists from Cardiff University believe that a treatment to prevent or delay the symptoms of Huntington’s disease could now be much closer, following a major breakthrough.
The Genetic Roots of Adolescent Scoliosis
Scientists at the RIKEN Center for Integrative Medical Sciences in collaboration with Keio University in Japan have discovered a gene that is linked to susceptibility of Scoliosis.
A Gene-Sequence Swap Using CRISPR to Cure Haemophilia
For the first time chromosomal defects responsible for hemophilia have been corrected in patient-specific iPSCs using CRISPR-Cas9 nucleases
New Tool Uses 'Drug Spillover' to Match Cancer Patients with Treatments
Researchers have developed a new tool that improves the ability to match drugs to disease: the Kinase Addiction Ranker (KAR) predicts what genetics are truly driving the cancer in any population of cells and chooses the best "kinase inhibitor" to silence these dangerous genetic causes of disease.
Understanding the Molecular Origin of Epigenetic Markers
Researchers at IRB Barcelona discover the molecular mechanism that determines how epigenetic markers influence gene expression.
New Tech Enables Epigenomic Analysis with a Mere 100 Cells
A new technology that will dramatically enhance investigations of epigenomes, the machinery that turns on and off genes and a very prominent field of study in diseases such as stem cell differentiation, inflammation and cancer has been developed by researchers at Virginia Tech.
Access Denied: Leukemia Thwarted by Cutting Off Link to Environmental Support
A new study reveals a protein’s critical – and previously unknown -- role in the development and progression of acute myeloid leukemia (AML), a fast-growing and extremely difficult-to-treat blood cancer.
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!