Accidental exposure to high-dose radiation while pregnant has shown significant negative effects on the developing fetus. One fetal organ which has been studied is the placenta. The placenta performs all essential functions for fetal development, including nutrition, respiration, waste excretion, endocrine communication, and immunological functions. Improper placental development can lead to complications during pregnancy, as well as the occurrence of intrauterine growth-restricted (IUGR) offspring. IUGR is one of the leading indicators of fetal programming, classified as an improper uterine environment leading to the predisposition of diseases within the offspring. With numerous studies examining fetal programming, there remains a significant gap in understanding the placenta’s role in irradiation-induced fetal programming. This review aims to synthesize current knowledge on how irradiation affects placental function to guide future research directions. This review provides a comprehensive overview of placental biology, including its development, structure, and function, and summarizes the placenta’s role in fetal programming, with a focus on the impact of radiation on placental biology. Taken together, this review demonstrates that fetal radiation exposure causes placental degradation and immune function dysregulation. Given the placenta’s crucial role in fetal development, understanding its impact on irradiation-induced IUGR is essential.

The gas transmitters nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H₂S) play important roles in physiological regulation, including adrenal function. Among them, only NO has been directly implicated in controlling catecholamine biosynthesis. This study examined whether CO and H₂S exert similar effects by treating PC12 cells with a CO donor (CORM-2) or an H₂S donor (NaHS), with or without glucocorticoid stimulation. Gene expression of tyrosine hydroxylase (Th), dopamine β-hydroxylase (Dbh), and phenylethanolamine N-methyltransferase (Pnmt) was assessed by RT-qPCR, and catecholamine release was measured by ELISA. We found that exogenous CO decreased Th and Dbh expression, attenuated glucocorticoid-induced upregulation of catecholamine biosynthesis genes, and differentially modulated dopamine and norepinephrine release. In contrast, exogenous H₂S treatment had no significant effect. These findings identify CO as a novel regulator of catecholamine biosynthesis and highlight important differences among gas transmitters in stress-related signaling.

High doses of ionizing radiation during prenatal development can cause growth restriction, or a decrease in growth of the developing offspring. This outcome of intrauterine growth restriction (IUGR) can predispose the offspring to lifelong health outcomes, which is referred to as developmental programming. The role of the placenta in radiation-induced IUGR was investigated using a mouse model. Pregnant BALB/cAnNCrl mice were externally irradiated with 1.82 Gy x-ray irradiation on gestational day 14.5. Fetoplacental units were collected on gestational day 18.5, and growth restriction was observed in irradiated offspring. Whole placenta samples from growth restricted and sham-irradiated groups were analyzed via RNA-sequencing analysis. Differential gene expression (DEG) analysis revealed a total of 166 DEGs in the irradiated samples. Validation of these DEG findings were completed using RT-qPCR analysis. Gene ontology (GO) analysis of the DEGs supported the involvement of autoimmune response and dysregulation in retinol (vitamin A) metabolism in the placenta. Upstream prediction analysis identified a number of potential regulators responsible for the DEG profiles including Nppb, Myod1 and genes of the classic complement system (Complement C1q chains C1qa, C1qb, C1qc). Overall, these findings present an overview of the dysregulation in the mouse placenta following an acute, high-dose radiation exposure.

Candida auris is a multidrug-resistant fungal pathogen for which echinocandins are recommended first-line therapy, yet its adaptive responses to this drug class remain incompletely understood. This study defined the genome-wide transcriptional responses of C. auris strain B11244 (Clade IV) to subinhibitory caspofungin, micafungin, and anidulafungin and examined whether shared responses corresponded to cell-wall remodeling. Growth-based broth microdilution indicated susceptibility to all three drugs by MIC (caspofungin, approximately 0.5–1 µg/mL; micafungin, 0.125 µg/mL; anidulafungin, approximately 0.03125 µg/mL), but caspofungin uniquely produced marked paradoxical growth at 4–8 µg/mL, consistent with caspofungin tolerance. RNA sequencing identified 2920, 2130, and 2149 differentially expressed genes following caspofungin, micafungin, and anidulafungin exposure, respectively, including 283 co-upregulated and 157 co-downregulated genes. All three drugs induced a conserved cell-wall integrity program marked by transcriptional induction of Bck1-Mkc1 and Hog1 MAPK pathway components and an 18-gene signature involved in chitin synthesis and cell-wall cross-linking. The response was strongest with caspofungin, and RT-qPCR corroborated representative transcriptional changes. No canonical FKS1 hotspot mutation was detected; an I1572L substitution was predicted to be structurally neutral. Calcofluor White microscopy showed qualitatively enhanced peripheral fluorescence following each treatment, whereas colorimetric glucosamine measurement demonstrated significantly increased bulk chitin only with caspofungin (149% of control); micafungin (120%) and anidulafungin (98%) did not differ significantly from control. Taken together, these findings are consistent with inducible, MAPK-associated cell-wall remodeling as a potential FKS1-independent contributor to echinocandin tolerance, while showing that transcriptional convergence does not imply uniform phenotypic outcomes.