Breaking News
October 15, 2018 - FDA Approves Yutiq (fluocinolone acetonide intravitreal implant) for Chronic Non-Infectious Posterior Segment Uveitis
October 15, 2018 - Birthing Options for Full-Term Pregnancy
October 15, 2018 - Stressed, toxic, zombie cells seen for first time in Alzheimer’s
October 15, 2018 - Concussion researchers study head motion in high school football hits | News Center
October 15, 2018 - Neuropsychiatric symptoms related to earliest stages of Alzheimer’s brain pathology
October 15, 2018 - Neck collar device may help protect the brain of female high school soccer players
October 15, 2018 - Research reveals how the inner ear processes speech
October 15, 2018 - Many parents still skeptical about safety and effectiveness of flu shot, survey finds
October 15, 2018 - Payer Policies May Discourage Non-Pharma Tx for Low Back Pain
October 15, 2018 - Exercise may delay cognitive decline in people with rare Alzheimer’s disease
October 15, 2018 - Researchers modify CRISPR to reorganize genome | News Center
October 15, 2018 - Innovative brain tumor operation set to tailor to patients’ needs
October 15, 2018 - Findings offer new insight into early changes that occur during AD pathology
October 15, 2018 - Neurons regulating reproductive hormone release have different activity in epileptic mice
October 15, 2018 - More parents are concerned about taking babies swimming in public pools
October 15, 2018 - Health Tip: Know the Risk Factors for Lower Back Pain
October 15, 2018 - Study shows cigarillo flavors enhanced by high-intensity sweeteners
October 15, 2018 - Study traces hospital-acquired bloodstream infections to patients’ own bodies | News Center
October 15, 2018 - Abnormal vision in childhood can affect development of brain areas responsible for attention
October 15, 2018 - Color-changing contact lens could help doctors to monitor eye disease medications
October 15, 2018 - Tobacco heating products cause less staining to teeth than conventional cigarettes
October 15, 2018 - Young adults who are obese can expect to lose up to 10 years in life expectancy
October 15, 2018 - Scientists uncover how proteins meet on the cell membrane
October 15, 2018 - Affordable housing with supportive social services for senior citizens can reduce hospital use
October 15, 2018 - Schiller Easy Pulse Saves Lives
October 15, 2018 - The latest ECG device from Schiller
October 15, 2018 - Following a Tissue Sample
October 15, 2018 - Prisoners need drug and alcohol treatments but AA programs aren’t the answer
October 15, 2018 - Andrea Califano and Jordan Orange Elected to National Academy of Medicine
October 15, 2018 - The impending risk of African Swine Fever Virus
October 15, 2018 - Breastfeeding reduces the number of antibiotic-resistant bacteria in infant gut
October 15, 2018 - Researchers develop comprehensive molecular atlas of postnatal mouse heart development
October 15, 2018 - ObsEva SA Presents Clinical Data from Phase III IMPLANT 2 Trial of Nolasiban in IVF at the American Society of Reproductive Medicine (ASRM) Annual Meeting
October 15, 2018 - Engineering teratoma-derived fibroblasts to enhance osteogenesis
October 15, 2018 - Lab study shows effectiveness of potential therapy for treatment-resistant hypothyroidism
October 15, 2018 - JCU study firms up association between diet and depression
October 15, 2018 - Researchers to study the use of CRISPR on human liver on-a-chip platform
October 15, 2018 - Sub-concussive impacts not associated with decline in neurocognitive function
October 15, 2018 - Researchers find potential treatment to halt premature labor and birth
October 15, 2018 - As U.S. suicides rates rise, Hispanics show relative immunity
October 15, 2018 - FDA Issues a Complete Response Letter to Acacia Pharma for Barhemsys
October 15, 2018 - Photoactive bacteria bait may help in fight against MRSA infections
October 15, 2018 - Increasing vigorous exercise reduces risk factors of type 2 diabetes, cardiovascular disease in children
October 15, 2018 - First-of-its-kind study to test a personalized vaccine in cancer patient
October 15, 2018 - Extension trial assesses benefit of switching from flash monitoring to RT-CGM for hypoglycemia
October 15, 2018 - Half of parents say young children are afraid of doctor’s visits
October 15, 2018 - Study shows how fingerprint-based drug screening works on the living and deceased
October 15, 2018 - Study reveals potential to monitor progression of Alzheimer’s disease by measuring brain antioxidant levels
October 15, 2018 - FDA Approves Xarelto to Reduce the Risk of Major Cardiovascular Events in Patients with Chronic Coronary Artery Disease (CAD) or Peripheral Artery Disease (PAD)
October 15, 2018 - Promising new therapeutic approach against Ebola virus identified
October 15, 2018 - Study unravels how cancer stem cells use normal genes in abnormal ways
October 15, 2018 - Healthcare systems fail to deliver at affordable prices finds report
October 15, 2018 - Intensive BP Therapy in Diabetes May Lower Risk for CV Events
October 15, 2018 - Muscle relaxants increase risk of respiratory complications
October 15, 2018 - Female birds become more promiscuous after hatchings fail in the first breeding attempt
October 15, 2018 - Humans occupied Madagascar thousands of years later than previously thought
October 15, 2018 - Is Kidney Dialysis Always Needed When Septic Shock Strikes?
October 15, 2018 - Study shows invasive lung cancer surgery can lead to long-term opioid use
October 15, 2018 - Sugar, a “sweet” tool to understand brain injuries
October 14, 2018 - King’s commemorates activities and research on World Arthritis Day
October 14, 2018 - Humana and VFW NY team up on Stop 22 initiative to increase awareness of veterans committing suicide
October 14, 2018 - Water fluoridation contributes to urinary fluoride levels in pregnant women in Canada
October 14, 2018 - Study of children in Romanian orphanages tells cautionary tale about family separation
October 14, 2018 - Previous Endologix AFX Safety Notice classified by FDA as Class I recall
October 14, 2018 - Legal scholars sound alarm on academies’ report about returning research results to participants
October 14, 2018 - UNIST selects six extraordinary scholars to be induced as ‘Rising-star Distinguished Professor’
October 14, 2018 - Scientists find new way to help asthmatics breathe more easily
October 14, 2018 - New ‘gag rule’ may adversely impact health care of pregnant women
October 14, 2018 - Rosacea – Genetics Home Reference
October 14, 2018 - When the fighting crosses the line
October 14, 2018 - New findings could benefit patients with triple-negative breast cancer
October 14, 2018 - UK Biobank provides wealth of information for further genetic studies
October 14, 2018 - KHN’s ‘What the Health?’ Falling premiums and rising political tensions
October 14, 2018 - Duvelisib Promising for Chronic Lymphocytic Leukemia, SLL
October 14, 2018 - Tailored drug cocktails offer hope to kids with aggressive brain tumors
October 14, 2018 - Common gene variants linked to migraine risk in African-American children
October 14, 2018 - Funding requests are being accepted by BlueCross BlueShield of Tennessee Community Trust
October 14, 2018 - Using pulsed electric fields in cancer therapy
October 14, 2018 - Major Childbirth Complications More Likely for Black Women
October 14, 2018 - Young cancer survivors at greater risk of mental health disorders
Researchers insert just enough human DNA into mice to study preterm birth

Researchers insert just enough human DNA into mice to study preterm birth

image_pdfDownload PDFimage_print

Preterm birth remains a global epidemic linked to a lifetime of potential health complications. It also is difficult to study in living creatures–especially the uniquely precise biology of preterm birth in humans.

Researchers report in PLoS Biology successfully inserting just enough human DNA into transgenic laboratory mice that it allowed the team to study a unique part of human pregnancy compared to other animals.

As a result, the scientists at the Cincinnati Children’s Perinatal Institute and Department of Pediatrics at the University Of Cincinnati College Of Medicine discovered what controls expression of a stress hormone called corticotrophin-releasing hormone (CRH) in the placenta. The placenta supports the fetus and provides communication with the mother.

CRH expression levels are linked to birth timing in humans and indicate whether a pregnancy will be preterm, post-term, or the normal term of 37-42 weeks. Unfortunately, pregnant mice and other non-primate species don’t naturally express CRH in the placenta. The scientists had to figure out how to get the animals to incorporate the genetic machinery needed to express the hormone.

This is important because researchers still don’t know what CRH does in the placenta during pregnancy. Having transgenic mice with the necessary human DNA to express CRH in the placenta should help them find out, according to Louis Muglia, MD, senior investigator on the study, Co-Director of the Perinatal Institute and Director of Human Genetics at Cincinnati Children’s.

“The challenge with studying human pregnancy is the typical biomedical approach requires a relevant animal for research,” Muglia said. “It’s been done for cancer and many other diseases. The problem is pregnancy in humans is different enough that it’s not been possible to effectively translate the findings from the animal studies to humans.”

Transgenic mouse models that mimic key aspects of human pregnancy also should help researchers uncover more information about how epigenetics affect birth timing. This could help answer long-standing questions about whether environmental exposures, like social stress or poor nutrition, influence the expression of genes important to birthing healthy, full-term babies.

Nature Finds a Way

To get pregnant laboratory mice to express CRH, Muglia’s team decided to test evolutionary genetics and biology. They experimented with something called a retroviral long terminal repeat (LTR) known as THE1B.

Retroviral LTRs are identical sequences of DNA that continually repeat themselves and allow viruses to insert their genetic material into the genome of a host species. In the case of THE1B, it jumped into the genome of anthropoid primates (humankind’s closest evolutionary relatives) 50 million years ago.

The research team developed a hypothesis that THE1B’s invasion of the anthropoid primate genome may have initiated CRH expression in the placenta during pregnancy.

They tested this by microinjecting into transgenic mice 180 kilobytes of human DNA containing the THE1B LTR and CRH. Muglia said researchers didn’t know if it would work, but in a vivid display of genetic adaptability the mice integrated and activated the DNA in the placenta.

“We were fortunate that the mice already had the machinery waiting and ready to activate and incorporate the human DNA and CRH in their placenta during pregnancy,” he said.

Glimpse of Pregnancy Control

After the human DNA was up and running in the mouse placentas, the researchers selectively edited DNA regions of THE1B with a precise gene-editing technique called CRISPR/Cas9. They found that the restricted deletion of THE1B silenced CRH expression and normalized birth timing in the transgenic mice.

Their data also uncovered an interaction between THE1B and a transcription factor called DLX3, which is expressed in the placenta. Transcription factors in essence are genes that tell other genes what to do. During pregnancy, DLX3 is critical to normal development of the placenta.

Collectively the study’s findings suggest that retroviral insertion of THE1B into the anthropoid genome initiated CRH expression in the placenta by working with DLX3. The data also suggest that intentionally manipulating placental CRH levels can alter the timing of birth. The authors stress the current study is still early and its findings are a small part of a large and complex puzzle that requires more research.

In their ongoing studies of CRH, THE1B and DLX3, the scientists will use this new information to explore how these biological pieces fit into the complex puzzle of what controls the timing of human pregnancies.

Source:

https://www.cincinnatichildrens.org/

Tagged with:

About author

Related Articles