From the Cover: Usage of Dexamethasone Increases the Risk of Cranial Neural Crest Dysplasia in the Chick Embryo

Abstract

Dexamethasone (Dex) is commonly used in the treatment of a variety of benign and malignant conditions. Unfortunately, although it has a variety of teratogenic effects, it remains used in clinical practice for pregnant women mainly due to limited alternatives. However, there is limited knowledge of the mechanisms that lead to the observed teratogenic effects. In this study, the effects of Dex during embryogenesis on neural crest development were evaluated in the early chick embryos. First, we demonstrated that 100 µl 10-6 M Dex treatment leads to craniofacial developmental defects, and also retards embryo growth and plausibly can cause embryo demise. Second, we demonstrated that Dex represses the production of HNK-1, PAX7, and AP-2α labeled cranial neural crest cells, the progenitor cells of the craniofacial skeleton. Third, double immunofluorescent staining of pHIS3/PAX7 and AP-2α/c-Caspase3 revealed that Dex promotes cell apoptosis but does not change cell proliferation rates. Last, fibroblast growth factor signaling molecules were inhibited by Dex treatment. Dex also inhibited neural crest cells production by repressing Msx1 expression in the developing neural tube and by altering expression of epithelial-mesenchymal transition-related adhesion molecules and cell migration genes. Overall, we obtained experimental evidence that Dex treatment during embryogenesis disrupts cranial neural crest development which in turn causes defective cranial bone development.

Local Glucocorticoid Administration Impairs Embryonic Wound Healing

“…Human fetal malformations caused by first-trimester systemic glucocorticoid administration, such as cleft lip as an example of cranial defects [ 33 ], can be reproduced and more thoroughly investigated in the avian embryo, employing molecular biological techniques [ 34 ].…”

HELLS, a chromatin remodeler is highly expressed in pancreatic cancer and downregulation of it impairs tumor growth and sensitizes to cisplatin by reexpressing the tumor suppressor TGFBR3

“…In China, the estimated new cases of PC numbered 90.1 per 100,000 people, and the number of deaths was 79.4 per 100,000 in 2015 2 . PC is poorly responsive to radiation therapy and targeted therapy; hence, combination systemic chemotherapy involving drugs, such as cisplatin, gemcitabine, capecitabine, and oxaliplatin, is the last option for patients with an advanced stage or metastasis 3,4 . Although an overall survival increase is provided by chemotherapy, the relatively limited patient benefit and predictive markers suggesting individual benefit from chemotherapy are still scarce for PC 5 .…”

“…2 PC is poorly responsive to radiation therapy and targeted therapy; hence, combination systemic chemotherapy involving drugs, such as cisplatin, gemcitabine, capecitabine, and oxaliplatin, is the last option for patients with an advanced stage or metastasis. 3,4 Although an overall survival increase is provided by chemotherapy, the relatively limited patient benefit and predictive markers suggesting individual benefit from chemotherapy are still scarce for PC. 5 Thus, a better understanding of the molecular mechanisms underlying tumorigenesis and screening for suitable biomarkers for chemotherapy response are essential for PC patients.…”

Dexamethasone interferes with osteoblasts formation during osteogenesis through altering IGF‐1‐mediated angiogenesis

“…Dex is also one of the most powerful drugs to reduce the risk of neonatal respiratory distress syndrome during the perinatal and neonatal periods. Despite all this, its clinical application during the perinatal period has attracted great concerns, because indiscriminate Dex application could teratogenically cause palate cleft or other craniofacial dysplasia in developing fetus (Azziz & Ladda, 1990;Cheng et al, 2017). Therefore, more systematically investigating of Dex on embryonic osteogenesis should be implemented for better guidance of clinical personalized treatment.…”