Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

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

Join For Free

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 3,500+ scientific posters on ePosters
  • More Than 5,100+ 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 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

Structure of Primary Cannabinoid Receptor is Revealed
The findings provide key insights into how natural and synthetic cannabinoids including tetrahydrocannabinol —a primary chemical in marijuana—bind at the CB1 receptor to produce their effects.
Friday, October 21, 2016
NIH Study Determines Key Differences between Allergic and Non-Allergic Dust Mite Proteins
Researchers at NIH have uncovered factors that lead to the development of dust mite allergy and assist in the design of better allergy therapies.
Thursday, October 20, 2016
NIH Contributes to Global Effort to Prevent and Manage Lung Diseases
The large scale trial will measure health benefits of clean cookstoves.
Thursday, October 20, 2016
Untangling Cause Of Memory Loss In Neurodegenerative Diseases
NIH-funded mouse study identifies a possible therapeutic target for a family of disorders.
Tuesday, October 18, 2016
NIH Scientists Uncover Genetic Explanation for Frustrating Syndrome
Researchers at NIH have suggested that the multiple alpha tryptase gene copies might underlie health issues that affect a substantial number of people.
Tuesday, October 18, 2016
Scientists at NIH and Emory Achieve Sustained SIV Remission in Monkeys
The finding suggest that the immune systems of these animals are controlling SIV replication in the absence of antiretroviral therapy.
Friday, October 14, 2016
Untangling a Cause of Memory Loss in Neurodegenerative Diseases
The mouse study identifies a possible therapeutic target for a family of disorders.
Thursday, October 13, 2016
Visual Cortex Plays Role in Plasticity of Eye Movement Reflex
Researchers at NIH have found that the visual cortex region of the brain known to process sensory information plays a vital role in promoting the plasticity of innate, spontaneous eye movements.
Thursday, October 13, 2016
NIH Commits $6.7 M to Advance DNA, RNA Sequencing Technology
"Can you believe they make DNA sequencers the size of staplers?" asked Meni Wanunu, Ph.D. "Ideas that were crazy twenty years ago are now happening!"
Friday, October 07, 2016
Cone Snail Venom Reveals Insulin Insights
Researchers found that a fast-acting insulin from the cone snail can bind and activate the human insulin receptor.
Wednesday, October 05, 2016
DNA Vaccines Protect Monkeys Against Zika Virus
Two experimental Zika virus DNA vaccines developed by NIH scientists protected monkeys against Zika infection.
Wednesday, October 05, 2016
Targeting Cardiovascular Disease Risk Factors May be Important Across a Lifetime
The study suggests efforts to prevent risk factors should extend to those older than 65.
Tuesday, October 04, 2016
Researchers Find a Gap in the Brain’s Firewall Against Parkinson’s Disease
Researchers at NIH have found mouse study that identified a key player in the progression of the disorder.
Saturday, October 01, 2016
Drug to Treat Alcohol Use Disorder Shows Promise Among Drinkers With High Stress
The findings suggest that potential future studies with drugs targeting vasopressin blockade should focus on populations of people with AUD who also report high levels of stress.
Friday, September 30, 2016
Monkeys Protected by Zika DNA Vaccine
Experimental Zika virus DNA vaccines successfully protected monkeys against Zika infection.
Thursday, September 29, 2016
Scientific News
Integrated Omics Analysis
Studying multi-omics promises to give a more holistic picture of the organism and its place in its ecosystem, however despite the complexities involved those within the field are optimistic.
Unravelling the Role of Key Genes and DNA Methylation in Blood Cell Malignancies
Researchers from the University of Nebraska Medical Center have demonstrated the role of Dnmt3a in safeguarding normal haematopoiesis.
Salford Lung Study - The First Real World Clinical Trial
In this podcast, we learn about the Salford Lung Study and its potential to revolutionize the way we assess new drugs and treatments around the world.
Point of Care Diagnostics - A Cautious Revolution
Advances in molecular biology, coupled with the miniaturization and improved sensitivity of assays and devices in general, have enabled a new wave of point-of-care (POC) or “bedside” diagnostics.
Mass Spec Technology Drives Innovation Across the Biopharma Workflow
With greater resolving power, analytical speed, and accuracy, new mass spectrometry technology and techniques are infiltrating the biopharmaceuticals workflow.
Structure of Primary Cannabinoid Receptor is Revealed
The findings provide key insights into how natural and synthetic cannabinoids including tetrahydrocannabinol —a primary chemical in marijuana—bind at the CB1 receptor to produce their effects.
Illumina Contributes to ClinVar Database
The contribution includes variants of all classifications, from pathogenic to benign, identified during interpretation of whole genome sequences generated in the CLIA-certified, CAP-accredited Illumina Clinical Services Laboratory.
Overlooked Molecules Could Revolutionise our Understanding of the Immune System
Researchers have discovered that around one third of all the epitopes displayed for scanning by the immune system are a type known as ‘spliced’ epitopes.
Study Finds Key Regulator in Pulmonary Fibrosis
Researchers identify an enzyme that could open the way to therpies for chronic fatal lung disease.
Signaling Pathway Could Be Key to Improved Osteoporosis Treatment
Inhibition of SIK2 enzyme both stimulates bone formation and reduces bone breakdown in animal model.
Scroll Up
Scroll Down
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
3,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,100+ scientific videos