Compared to the exposure to the external environment whether

Compared to the exposure to the external environment, whether and how the internal endocrine environment can illicit intergenerational effects is less understood. Hyperandrogenism is a common endocrine disorder that happens in 5–10% of reproductive-aged women. Previous animal studies suggest that intrauterine exposure to elevated androgen levels could impair glucose tolerance in offspring (). Whether this is true in human has not been determined. In this issue of , a research team at the International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University addresses this important question (). They measured basal blood androgen levels in pre-gestational women and then performed glucose tolerance tests in their children at the age of 5years. Total of 156 children from 147 women with hyperandrogenism (testosterone>2.4nmol/L or dehydroepiandrosterone>8.8μmol/L) were tested, while 1060 children from 969 women served as control. They found that maternal hyperandrogenism significantly increased the chance, by nearly 4-fold, of developing prediabetes in offspring children (fasting glucose 5.6–6.9mmol/L). In addition, children born to the mothers with pregestational hyperandrogenism have significantly higher glucose and insulin levels during oral glucose tolerance tests, suggesting development of insulin resistance. To explore the underlying molecular mechanism, the authors checked DNA methylation at imprinted genes previously implicated in pathogenesis of diabetes (). They found that children born to mothers with pre-gestational hyperandrogenism have lower DNA methylation levels and higher gene S63845 levels in two imprinted genes Igf2 (Insulin-like growth factor 2) and Grb10 (Growth factor receptor-bound protein 10) in blood lymphocytes. The authors went on to show that the lower DNA methylation levels and higher gene expression levels of Igf2 occurred in both F0 oocytes and F1 pancreatic islets in a rat model of pre-gestational hyperandrogenism, which further supports a gamete-mediated mechanism in this maternal effect. These findings also suggest that pancreatic islets is a major target tissue contributing to the glucose intolerance phenotype in F1 offspring. The nice study by Tian et al. raised several interesting questions that warrant future investigation. Is the pancreatic defect a cause of prediabetes in the F1 offspring? A clear defect in glucose-stimulated insulin secretion (GSIS) was observed in the F1 offspring in rat, but not in human. In addition, how does hyperandrogenism alter DNA methylation or change DNA methyltransferase expression in oocytes? Can the change in Igf2 and Grb10 gene expression fully explain the pre-diabetes phenotype in the F1 offspring? Would the F1 metabolic phenotype be rescued by correcting the DNA methylation changes in either oocyte or pancreas using epigenome-editing techniques in the animal model? Disclosure
In this issue of , ), used a proteomic profiling approach to report the identification and validation of PDZ domain containing 1 (PDZK1) as a poor prognostic marker for clear cell renal cell carcinoma (ccRCC). This work elegantly highlights the use of quantitative proteomics for cancer biomarker discovery and further validation using multiple patient cohorts.
In 2015, there were over 10 million cases of tuberculosis, with a resulting 1.8 million deaths, making TB the biggest infectious disease killer today (). Early diagnosis leading to timely and appropriate treatment of TB is an essential pillar of the End TB strategy, but completion of this foundational step in the TB cascade of care is often difficult (). Smear microscopy, still the most frequently utilized diagnostic technique for TB, has low sensitivity; microbiological culture takes weeks to produce results; Xpert MTB/RIF is often inaccessible due to both cost and location (). In response to these circumstances, researchers have turned to the host response to TB in an effort to identify biomarkers upon which new diagnostic techniques may be based.