Evaluation of kisspeptin-54 for egg maturation

In virto fertilization (IVF) has helped millions of couples have children. While considered relatively safe, there are risks associated with this procedure. Among the more serious complications is the development of ovarian hyperstimulation syndrome (OHSS), which in extreme cases can be fatal. OHSS results from excessive stimulation of the luteinizing hormone (LH) receptor by human chorionic gonadotropin (hCG), which is commonly used as part of the IVF cycle to promote egg maturation. In this episode, Waljit Dhillo discusses the results from a small clinical trial that evaluated use of the fertility hormone kisspeptin-54 for egg maturation in IVF. Dhillo and colleagues report that kisspeptin-54 treatment resulted in mature eggs that were successfully fertilized and transferred, with pregnancy in 23% of patients.

Unraveling profibrotic pathways in the kidney

Fibrosis is a hallmark of chronic kidney disease that is characterized by accumulation of extracellular matrix and an influx of immune cells. Autophosphorylation of serine residues within the type II TGF-β receptor (TβRII) following activation by TGF-β induces a SMAD-dependent profibrotic signaling cascade; however, there are multiple tyrosine residues within the cytoplasmic tail of TβRII that have potential to regulate this pathway. In this episode, Ambra Pozzi reveals that phosphorylation of tyrosine residues in the cytoplasmic tail of TβRII does influence the fibrotic signaling cascade. Specifically, Pozzi and colleagues determined that integrin α1β1 recruits the phosphatase TCPTP to TβRII, subsequently dephosphorylating tyrosine residues within the TβRII cytoplasmic tail. Furthermore, mice lacking α1β1 integrin exhibited enhanced phosphorylation of TβRII due to decreased recruitment of TCPTP, resulting in severe fibrosis following kidney injury.

MicroRNA-regulated network promotes pulmonary hypertension

Pulmonary hypertension is a complex disease that affects multiple vascular cell types, and mircoRNAs (miRNAs) have been implicated in the pathogenesis of this condition. In this episode, Stephen Chan discusses how his group used network theory to identify miRNA-130/301 as a regulator of a system of miRNAs that promote the development of pulmonary hypertension. Furthermore, inhibition of miR130/301 prevented the development on pulmonary hypertension in a hypoxic murine model. The results of this study support the use of network analysis for identifying complex miRNA-regulated pathways involved in disease manifestations.

Maternal B12 status influences offspring bone mass

The maternal environment not only affects in utero development, but also can dramatically influence postnatal phenotypes.  In this episode, Vijay Yadav, Isabel Quiros-Gonzalez, and Liesbet Lieben discuss their use of a murine genetic model to evaluate the effects of maternal vitamin B₁₂ deficiency on offspring bone formation. Pups from B₁₂-deficient mothers exhibited growth retardation and reduced bone mass due to a loss of taurine synthesis in the liver. Furthermore, administration of taurine to these offspring enhanced bone formation, ameliorating growth defects. The results from this study suggest that B₁₂/taurine supplementation may be a potential therapeutic strategy to increase bone mass.

Epigenetic consequences of disturbed blood flow

The development of atherosclerotic plaques typically occurs in regions of arteries that have disturbed blood flow. While blood flow disturbances are known to alter endothelial gene expression and function, it is not clear how altered blood flow induces these changes. In this episode, Hanjoong Jo presents evidence that blood flow disturbances alter genome-wide methylation patterns in endothelial cells through induction of the DNA methyltransferase DNMT. Long-term epigenetic changes induced within the arterial endothelium may lead to development of atherosclerosis, and genes that are altered in response to disturbed flow represent potential therapeutic targets for limiting plaque formation.