FNDC5

NIH findings may lead to insights on pregnancy complications, adult health BETHESDA, Md., May 2, 2025 /PRNewswire-HISPANIC PR WIRE/ -- What: The genes of male and female placentas have marked differences in how they are expressed, according to a study by researchers at the National Institutes of Health (NIH) and other institutions. These differences involve the presence or absence of tags on DNA known as methyl groups, which switch genes on or off without changing their structure. Understanding these DNA methylation patterns may inform future research on the higher risk for pregnancy complications involving male fetuses, such as stillbirth and prematurity, as well as later life health conditions that occur in adults who were born after a complicated pregnancy. Researchers analyzed male and female placental samples from a larger study for differences in their methylation patterns, and found differences in gene activity between male and female placentas that may play a role in birthweight and adult diseases. The study identified 2,497 previously unreported DNA sites that had different methylation patterns for males and females. Of these and more than 2,500 sites that had also been identified by previous studies, 66.9% of large increases in methylation occurred in DNA from male placentas and 33.1% from female placentas. Increases in methylation in male placentas was linked with greater neonatal size whereas those in females was linked with greater placental size. Some increases in methylation found in male placentas were located near the CCDC6 gene. Lower activation of CCDC6 has been linked with preterm birth in previous studies. Higher methylation near the FNDC5 gene was associated with lower expression of the gene in male placentas but not in female placentas. FNDC5 is involved with the manufacture of irisin, which protects the placenta from damage by reactive oxygen molecules and insulin resistance (cells' difficulty in using insulin to lower blood sugar.) Lower irisin levels have been associated with the pregnancy-related high blood pressure disorder, known as preeclampsia. Variations in the genes ATP5MG and FAM83A, expressed in female placentas, have been associated with asthma, hay fever, eczema (dry, itchy, inflamed skin) and higher risk for breast cancer later in life. Genetic factors influence the health differences between males and females, from before birth to later in life. Male fetuses grow faster than female fetuses and their pregnancies are more likely to be complicated by such conditions as preeclampsia (a hypertensive disorder of pregnancy), failure to grow at an adequate rate, and preterm birth. They also are more likely to die in the year after birth. Dysfunction of the placenta underlies many pregnancy complications and is thought to set the stage for male and female health differences that occur later in life. Variations in methylation patterns are thought to underlie many of these differences. The study was conducted by Fasil Tekola-Ayele, Ph.D., of the NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and colleagues at other institutions. It appears in Nature Communications. Who: Fasil Tekola-Ayele, Ph.D., is available for comment on this study. Reference Tekola-Ayele F, et al. Sex-differentiated placental methylation and gene expression regulation has implications for neonatal traits and adult diseases. Nature Communications. DOI: 10.1038/s41467-025-58128-3 (2025) SOURCE Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health (NIH) WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

As the days get shorter and chillier in the northern hemisphere, those who choose to work out in the mornings might find it harder to get up and running. A new study identifies a protein that, when missing, makes exercising in the cold that much harder--that is, at least in fruit flies. As the days get shorter and chillier in the northern hemisphere, those who choose to work out in the mornings might find it harder to get up and running. A new study in PNAS identifies a protein that, when missing, makes exercising in the cold that much harder -- that is, at least in fruit flies. A team from University of Michigan Medical School and Wayne State University School of Medicine discovered the protein in flies, which they named Iditarod after the famous long distance dog sled across Alaska, while studying metabolism and the effect of stress on the body. They were particularly interested in a physiological process called autophagy wherein damaged parts of cells are removed from the body. In screening the fly genome, they found a candidate for regulating the critical housekeeping procedure. They demonstrated the link between autophagy and Iditarod, or Idit, by tweaking the genetic makeup of some flies to overactivate autophagy in their eyes. Flies with too much autophagy had massive cell death leading to visible degeneration of the eye. Inactivating Idit gene restored the normal eye structure, indicating that Idit gene is involved in the autophagy process. The team's next step was to look for a similar gene, or homolog, in humans. "When we queried this gene in the human genome, a gene called FNDC5, which is a precursor to the protein irisin, was the top hit," said Jun Hee Lee, Ph.D, of the U-M Department of Molecular and Integrative Physiology. Previous research has shown irisin to be an important hormone involved in producing musculoskeletal and other benefits of exercise in mammals, as well as playing a role in adaptation to cold temperatures. Lee's lab had an existing interest in exercise as a mild form of bodily stress. "We realized this gene may be also important for exercise and if so, we should be able to detect a similar physiological effect in flies," said Lee. Working with Dr. Robert Wessells team at Wayne State University who developed a novel way to train fruit flies, the investigators used a sort of fly cliff climber that capitalizes on the insect's instinct to climb upward out of a test tube. They found that flies that were bred to lack the Idit gene had impaired exercise endurance, and lacked the improvement typically seen after training. Furthermore, irisin in mammals is known to upregulate thermogenic processes, which is critical for cold resistance. Interestingly, flies without Idit were also unable to tolerate cold. What this tells us, says Lee, is this gene family, present in invertebrates as well as mammals appears to have been conserved throughout evolution and serves an important function. "We believe that exercise helps clean the cellular environment through autophagy," said Lee. "When you are exercising hard, there is damage to the muscle and some of the mitochondria will malfunction," said Lee. "The autophagy process becomes activated to clean up any damaged organelles or toxic byproducts, and Idit gene seems important in this process." Lee hopes to next connect this work to their previous work on exercise and physiological stress. Additional authors include Tyler Cobb, Irene Hwang, Michael Soukar, Sim Namkoong, Uhn-Soo Cho4, and Myungjin Kim.