Breaking News
August 17, 2018 - Team explores diabetes drug’s ability to treat RSV infection
August 17, 2018 - New imaging technique can spot tuberculosis infection in an hour | News Center
August 17, 2018 - PolyU researchers design new self-fitting scaffold to induce bone regeneration
August 17, 2018 - CartiHeal and LSU Health successfully enroll first two patients in Agili-C IDE pivotal study
August 17, 2018 - Less-invasive options are slowing disease progression in glaucoma patients
August 17, 2018 - Researchers discover new promising target point for cancer and diabetes therapies
August 17, 2018 - Podcast: KHN’s ‘What the Health?’ See you in court!
August 17, 2018 - New mobile phone application enables early detection of cerebral ictus
August 17, 2018 - UK’s leading sight loss charity invites applications from brightest minds in ophthalmic research
August 17, 2018 - Researchers produce artificial placenta model that closely resembles natural organ
August 17, 2018 - FDA Alert: Temporary Total Artificial Heart Companion 2 Driver System by SynCardia Systems: Letter to Health Care Providers
August 17, 2018 - Researchers discover why sepsis from a staph infection causes organ failure
August 17, 2018 - Revealed: The molecular mechanism underlying hypertrophic cardiomyopathy | News Center
August 17, 2018 - Research explores relationship between personal history of infectious fever and cancer risk
August 17, 2018 - Study finds rise in cases of progressive massive fibrosis among U.S. coal miners
August 17, 2018 - NEDBELS project examines impact of neurodiversity concept on legal systems
August 17, 2018 - Seeking solutions to treat scleroderma
August 17, 2018 - Statins may improve conditions of people with rare lung disease
August 17, 2018 - Study finds why some people with brain markers of Alzheimer’s never develop dementia
August 17, 2018 - Life Biosciences contributes $100,000 to fund its biomedical innovation course on aging
August 17, 2018 - Researchers develop a set of health outcome measures for children with complex medical situations
August 17, 2018 - Many Americans Not Being Assessed for Depression
August 17, 2018 - Scientists report setbacks in quest for AIDS cure
August 17, 2018 - Christopher Gardner busts myths about milk | News Center
August 17, 2018 - Bacterial activity in child’s mouth may serve as biomarkers for autism spectrum disorder
August 17, 2018 - Scripps Research scientists uncover new approach for treating thrombocytopenia
August 17, 2018 - Mathematical model shows the influence of human behavior on spread of infectious diseases
August 17, 2018 - Valley Hospital achieves Magnet recognition for fourth consecutive time
August 17, 2018 - Researchers describe link between poor oocyte development and oxidative stress in obese mice
August 17, 2018 - Hospitals battle for control over fast-growing heart-valve procedure
August 17, 2018 - AHA: Home-Delivered Meals Keep Heart Failure Patients Out of Hospital
August 17, 2018 - In Southern Mozambique, only half of people diagnosed with HIV enroll in medical care
August 17, 2018 - Researchers discuss techniques to help combat growing epidemic of obesity
August 17, 2018 - Researchers develop novel statistical method to evaluate gene-to-gene interactions linked with cancer
August 17, 2018 - Island Fertility joins Stony Brook Community Medical to provide comprehensive fertility care
August 17, 2018 - Study shows link between thinning of the retina and early sign of Parkinson’s disease
August 17, 2018 - Digital birth control app gets FDA nod
August 17, 2018 - FDA grants approval for first generic version of epinephrine auto-injector
August 17, 2018 - Federal advisory group publishes recommendations on prevention of acute, chronic pain
August 17, 2018 - 3D-printed human body parts to be used as teaching aids for surgical training
August 17, 2018 - U.S. murder, suicide rates climbing again
August 17, 2018 - This is your brain on… roller coasters?
August 17, 2018 - Report discusses whether all newborns should undergo genetic sequencing
August 17, 2018 - UCR receives 2018 Inspiring Programs in STEM Award from INSIGHT Into Diversity magazine
August 17, 2018 - Researchers publish new paper on developing vaccine candidates for Helminthic parasites
August 17, 2018 - Researchers develop new method to diagnose broad range of cancers using malaria protein
August 17, 2018 - Female mosquitoes quickly evolve selective mating behavior when faced with threats
August 17, 2018 - FDA Grants Breakthrough Therapy Designation to Daiichi Sankyo’s FLT3 Inhibitor Quizartinib for Relapsed/Refractory FLT3-ITD AML
August 17, 2018 - Resistance training and exercise motivation go hand-in-hand
August 17, 2018 - A lesson for future doctors: Listen to and learn from your patients
August 17, 2018 - NUS study discovers a bidirectional regulator and shines light on A-to-I RNA editing in cancer cells
August 17, 2018 - Research shows link between high blood levels of omega-3s and better brain function in children
August 17, 2018 - Researchers propose new theory for how rare gene mutations cause Alzheimer’s disease
August 17, 2018 - New project to combat DMD-related fibrosis receives major funding boost
August 17, 2018 - Digital psychiatric therapy can ‘rewire’ the brain in children with ADHD, study shows
August 17, 2018 - Psychologist to assess how the brain maintains precise short-term and long-term memories
August 17, 2018 - Eating white button mushrooms could improve regulation of glucose in the liver
August 17, 2018 - Scientists identify mutational signatures in ovarian cancer
August 17, 2018 - Sun Pharma receives U.S. FDA approval for CEQUA to treat patients with dry eye disease
August 17, 2018 - Teva Announces Updated Indication and Vial Presentation for Granix (tbo-filgrastim) Injection in United States
August 17, 2018 - Study shows DNA methylation related to liver disease among obese patients
August 17, 2018 - Life on the border: Back at Stanford, ready to pitch in
August 17, 2018 - New device for accurately placing hemodialysis catheters on kidney patients
August 17, 2018 - New strategy accelerates, automates process of prototype molecule optimization
August 17, 2018 - Study finds role of autoimmunity in development of COPD
August 17, 2018 - Researchers transform research tool to study neuronal function
August 17, 2018 - Cognitive impairment does not equate to unhappiness in older adults
August 17, 2018 - Peer Comparisons Can Decrease Risky Prescribing Patterns
August 17, 2018 - Susceptible genes identified for childhood chronic kidney disease
August 17, 2018 - Research uncovers miscarriage cause, identifies potential targets for treatment
August 17, 2018 - Bacterial armor could be new target for antibiotics | News Center
August 17, 2018 - FDA expands approval of Vertex’ cystic fibrosis medicine to treat children aged 12 to
August 17, 2018 - Give Your Child a Head Start With Math
August 17, 2018 - Ground-breaking study tests whether rejected livers can be made viable for transplantation
August 16, 2018 - New algorithm could improve diagnosis of rare diseases | News Center
August 16, 2018 - SCHILLER introduces latest generation of ECG device, CARDIOVIT AT-102 G2
August 16, 2018 - Proper treatment, refraining from smoking can reduce heart disease risk from type 2 diabetes
August 16, 2018 - Mount Sinai study could transform treatment for patients with retinal degenerative diseases
August 16, 2018 - Penn researchers develop first mouse model of idiopathic pulmonary fibrosis
August 16, 2018 - Four tips to help prevent fall allergy symptoms
New UCLA study could elucidate certain causes of infertility and miscarriage

New UCLA study could elucidate certain causes of infertility and miscarriage

image_pdfDownload PDFimage_print

A new study in the journal Nature Cell Biology has uncovered information about a key stage that human embryonic cells must pass through just before an embryo implants. The research, led by UCLA biologist Amander Clark, could help explain certain causes of infertility and spontaneous miscarriage.

Infertility affects around 10 percent of the U.S. population, and roughly 15 to 20 percent of all pregnancies in the U.S. end in miscarriage. In many cases, the causes of infertility and miscarriage are unknown.

A team led by Clark, a UCLA professor of molecular cell and developmental biology and member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, set out to find how epigenomic changes -; non-genetic influences on gene expression -; in human embryonic stem cells could explain why some embryos are not viable.

They started by analyzing cells within the early embryo; these cells are pluripotent, meaning that they can turn into any cell within the human body.

“For many years, researchers thought that human pluripotency was a single state,” Clark said. “However, over the past three years, the field has discovered that human pluripotency involves at least two major states, and as embryos grow the stem cells pass through these two different states of pluripotency on the way to the embryo establishing a pregnancy.”

After a human embryo is fertilized and before it implants in the uterine lining, cells in the embryo are in a very immature state of pluripotency called the “naive” state. Little is known about the naive state, but scientists believe that if embryonic cells cannot first enter this state, the embryo is not viable and a miscarriage would occur. Around the time an embryo implants, its cells enter the “primed” state. Primed cells are ready to differentiate into all of the various cell types in the body.

“Although no one knows exactly why the naive state of pluripotency exists, or what helps naive cells stay in that state for a period of time, it could be to provide a protective mechanism that prevents the embryonic cells from differentiating too quickly, which would ensure the timing of implantation is right,” Clark said.

To better understand what helps regulate the naive state, the researchers compared epigenomic changes in lab-created naive and primed embryonic stem cells. They discovered that both cell types have different sequences of open chromatin throughout their DNA. Chromatin consists of DNA and protein that condense to form the chromosomes within a cell’s nucleus.

Unique sequences of open chromatin within any cell type act as bar codes. Gene-regulating proteins called transcription factors in the open areas of chromatin “scan” the bar code and then bind to it, which influences genetic activity in the cell.

“We looked specifically at open chromatin and found a bar code that is unique to naive embryonic stem cells repeated over and over again, so we asked what transcription factor recognizes that bar code,” Clark said.

The researchers discovered that a transcription factor called TFAP2C recognizes the bar code. To learn more about its specific role, they deleted the gene that makes the TFAP2C protein from both primed and naive embryonic stem cells in the laboratory using a gene editing tool called CRISPR-Cas9.

They found that the deletion had no effect on primed stem cells. Conversely, when TFAP2C was deleted from naive stem cells, the areas of open chromatin associated with the naive state closed and the naive stem cells passed into a primed state.

The research also revealed about 1,500 regions of open chromatin that are very sensitive to the loss of TFAP2C and showed that there are hundreds of genes associated with early embryonic development in those areas.

“We’ve discovered that the presence of TFAP2C marks an important difference between the naive and primed states of pluripotency, and that TFAP2C is necessary to maintain the naive state of pluripotency,” Clark said. “We also showed that without TFAP2C, hundreds of genes aren’t expressed correctly, which would most likely result in early miscarriage.”

In addition, the researchers verified that the regions of open chromatin present in lab-created naive embryonic stem cells are also present in embryos before the stage associated with implantation.

“Our findings are relevant to the natural process of human development because they match up with what we see in human pre-implantation embryos,” Clark said. “This provides new information about a time in the lifecycle that we know little about. Fundamental knowledge like this could help better predict infertility or embryo quality.”

The study also could lead to important advances in an area of medicine that historically has been underfunded and underappreciated -; in part because the subject of infertility is sometimes seen as taboo and because it doesn’t attract the attention of deadly diseases like cancer.

“People who experience infertility and miscarriage may tell close friends or family, but too often, these issues are not discussed,” Clark said. “But infertility is a significant health concern. It deserves our attention, and we as a society need to be more open about it.”

Source:

http://newsroom.ucla.edu/releases/ucla-research-may-explain-causes-of-infertility-or-miscarriage

Tagged with:

About author

Related Articles