Radiotherapy exposure directly damages the uterus and causes pregnancy loss

Female cancer survivors are significantly more likely to experience infertility than the general population. It is well established that chemotherapy and radiotherapy can damage the ovary and compromise fertility, yet the ability of cancer treatments to induce uterine damage, and the underlying mechanisms, have been understudied. Here, we show that in mice total-body γ-irradiation (TBI) induced extensive DNA damage and apoptosis in uterine cells. We then transferred healthy donor embryos into ovariectomized adolescent female mice that were previously exposed to TBI to study the impacts of radiotherapy on the uterus independent from effects to ovarian endocrine function. Following TBI, embryo attachment and implantation were unaffected, but fetal resorption was evident at midgestation in 100% of dams, suggesting failed placental development. Consistent with this hypothesis, TBI impaired the decidual response in mice and primary human endometrial stromal cells. TBI also caused uterine artery endothelial dysfunction, likely preventing adequate blood vessel remodeling in early pregnancy. Notably, when pro-apoptotic protein Puma-deficient (Puma–/–) mice were exposed to TBI, apoptosis within the uterus was prevented, and decidualization, vascular function, and pregnancy were restored, identifying PUMA-mediated apoptosis as a key mechanism. Collectively, these data show that TBI damages the uterus and compromises pregnancy success, suggesting that optimal fertility preservation during radiotherapy may require protection of both the ovaries and uterus. In this regard, inhibition of PUMA may represent a potential fertility preservation strategy.Meaghan J. Griffiths, Sarah A. Marshall, Fiona L. Cousins, Lauren R. Alesi, Jordan Higgins, Saranya Giridharan, Urooza C. Sarma, Ellen Menkhorst, Wei Zhou, Alison S. Care, Jacqueline F. Donoghue, Sarah J. Holdsworth-Carson, Peter A.W. Rogers, Evdokia Dimitriadis, Caroline E. Gargett, Sarah A. Robertson, Amy L. Winship, and Karla J. Hut

Bacterial strains from floodplain soils perform different plant-growth promoting processes and enhance cowpea growth

ABSTRACT Certain nodulating nitrogen-fixing bacteria in legumes and other nodule endophytes perform different plant-growth promoting processes. The objective of this study was to evaluate 26 bacterial strains isolated from cowpea nodules grown in floodplain soils in the Brazilian savannas, regarding performance of plant-growth promoting processes and ability to enhance cowpea growth. We also identified these strains by 16S rRNA sequencing. The following processes were evaluated: free-living biological nitrogen fixation (BNF), solubilization of calcium, aluminum and iron phosphates and production of indole-3-acetic acid (IAA). The abilities to nodulate and promote cowpea growth were evaluated in Leonard jars. Partial sequencing of the 16S rRNA gene identified 60 % of the strains as belonging to genus Paenibacillus. The following four genera were also identified: Bacillus, Bradyrhizobium, Enterobacter and Pseudomonas. None of the strains fixed N2 free-living. Among the strains, 80 % solubilized Ca phosphate and one solubilized Al phosphate and none solubilized Fe phosphate. The highest IAA concentrations (52.37, 51.52 and 51.00 μg mL−1) were obtained in the 79 medium with tryptophan by Enterobacter strains UFPI B5-7A, UFPI B5-4 and UFPI B5-6, respectively. Only eight strains nodulated cowpea, however, all increased production of total dry matter. The fact that the strains evaluated perform different biological processes to promote plant growth indicates that these strains have potential use in agricultural crops to increase production and environmental sustainability