FASEB bioAdvances最新文献

{"title":"Excitation and contraction of cardiac muscle and coronary arteries of brain-dead pigs","authors":"Per Arlock,&nbsp;Mei Li,&nbsp;Benjamin Davis,&nbsp;Cecilia Lövdahl,&nbsp;Qiuming Liao,&nbsp;Trygve Sjöberg,&nbsp;Awahan Rahman,&nbsp;Björn Wohlfart,&nbsp;Stig Steen,&nbsp;Anders Arner","doi":"10.1096/fba.2022-00104","DOIUrl":"10.1096/fba.2022-00104","url":null,"abstract":"<p>Excitability and contraction of cardiac muscle from brain-dead donors critically influence the success of heart transplantation. Membrane physiology, Ca²⁺-handling, and force production of cardiac muscle and the contractile properties of coronary arteries were studied in hearts of brain-dead pigs. Cardiac muscle and vascular function after 12 h brain death (decapitation between C2 and C3) were compared with properties of fresh tissue. In both isolated cardiomyocytes (whole-cell patch clamp) and trabecular muscle (conventional microelectrodes), action potential duration was shorter in brain dead, compared to controls. Cellular shortening and Ca²⁺ transients were attenuated in the brain dead, and linked to lower mRNA expression of L-type calcium channels and a slightly lower I_Ca,_L, current, as well as to a lower expression of phospholamban. The current–voltage relationship and the current above the equilibrium potential of the inward K⁺ (I_K1) channel were altered in the brain-dead group, associated with lower mRNA expression of the Kir2.2 channel. Delayed K⁺ currents were detected (I_Kr, I_Ks) and were not different between groups. The transient outward K⁺ current (I_to) was not observed in the pig heart. Coronary arteries exhibited increased contractility and sensitivity to the thromboxane analogue (U46619), and unaltered endothelial relaxation. In conclusion, brain death involves changes in cardiac cellular excitation which might lower contractility after transplantation. Changes in the inward rectifier K⁺ channel can be associated with an increased risk for arrhythmia. Increased reactivity of coronary arteries may lead to increased risk of vascular spasm, although endothelial relaxant function was well preserved.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"5 2","pages":"71-84"},"PeriodicalIF":2.7,"publicationDate":"2022-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2022-00104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9328834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell migration is impaired in XPA-deficient cells","authors":"Seiji Takeuchi,&nbsp;Takeshi Fukumoto,&nbsp;Chihiro Takemori,&nbsp;Naoaki Saito,&nbsp;Chikako Nishigori,&nbsp;Makoto Sato","doi":"10.1096/fba.2022-00084","DOIUrl":"10.1096/fba.2022-00084","url":null,"abstract":"<p>Xeroderma pigmentosum (XP) is a hereditary disorder characterized by photosensitivity, predisposition to skin cancers, and neurological abnormalities including microcephaly and progressive neurodegeneration. A lack of nucleotide excision repair (NER) in patients with XP can cause hypersensitivity to the sun, leading to skin cancer, whereas the etiology of the neuronal symptoms of XP remains ambiguous. There are various neurological disorders that perturb neuronal migration, causing mislocalization and disorganization of the cortical lamination. Here, we investigated the role of the XP group-A (<i>Xpa</i>) gene in directed cell migration. First, we adopted an in utero electroporation method to transduce shRNA vectors into the murine embryonic cerebral cortex for the in vivo knockdown of <i>Xpa</i>. <i>Xpa-</i>knockdown neurons in the embryonic cerebral cortex showed abnormal cell migration, cell cycle exit, and differentiation. The genotype–phenotype relationship between the lack of XPA and cell migration abnormalities was confirmed using both a scratch assay and time-lapse microscopy in XP-A patient-derived fibroblasts. Unlike healthy cells, these cells showed impairment in overall mobility and the direction of motility. Therefore, abnormal cell migration may explain neural tissue abnormalities in patients with XP-A.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"5 2","pages":"53-61"},"PeriodicalIF":2.7,"publicationDate":"2022-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/61/1b/FBA2-5-53.PMC9927838.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9328838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of 5-fluorodeoxyuridine monophosphate-thymidylate synthase ternary complex levels by autophagy confers resistance to 5-fluorouracil","authors":"Nana Nishizawa,&nbsp;Chinatsu Kurasaka,&nbsp;Yoko Ogino,&nbsp;Akira Sato","doi":"10.1096/fba.2022-00099","DOIUrl":"10.1096/fba.2022-00099","url":null,"abstract":"<p>5-Fluorouracil (5-FU) is a cornerstone drug used to treat colorectal cancer (CRC). However, the prolonged exposure of CRC cells to 5-FU results in acquired resistance. We have previously demonstrated that levels of the 5-fluorodeoxyuridylate (FdUMP) covalent complex with thymidylate synthase (FdUMP-TS) and free-TS (native enzyme) are higher in 5-FU-resistant CRC cells than in the parental cell line (HCT116). Accordingly, resistant cells may have an efficient system for trapping and removing FdUMP-TS, thus imparting resistance. In this study, using a model of 5-FU-resistant CRC cells generated by repeated exposure, the role of autophagy in the elimination of FdUMP-TS in resistant cells was investigated. The resistant cells showed greater sensitivity to autophagy inhibitors than that of parental cells. Autophagy inhibition increased 5-FU cytotoxicity more substantially in resistant cells than in parental cells. Furthermore, autophagy inhibition increased FdUMP-TS protein accumulation in resistant cells. Our findings suggest that resistance to 5-FU is mediated by autophagy as a system to eliminate FdUMP-TS and may guide the use and optimization of combination therapies involving autophagy inhibitors.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"5 1","pages":"43-51"},"PeriodicalIF":2.7,"publicationDate":"2022-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2022-00099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10589587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FtsZ phosphorylation brings about growth arrest upon DNA damage in Deinococcus radiodurans","authors":"Reema Chaudhary,&nbsp;Shruti Mishra,&nbsp;Ganesh K. Maurya,&nbsp;Yogendra S. Rajpurohit,&nbsp;Hari S. Misra","doi":"10.1096/fba.2022-00082","DOIUrl":"https://doi.org/10.1096/fba.2022-00082","url":null,"abstract":"<p>The polymerization/depolymerization dynamics of FtsZ play a pivotal role in cell division in the majority of the bacteria. <i>Deinococcus radiodurans</i>, a radiation-resistant bacterium, shows an arrest of growth in response to DNA damage with no change in the level of FtsZ. This bacterium does not deploy LexA/RecA type of DNA damage response and cell cycle regulation, and its genome does not encode SulA homologues of <i>Escherichia coli</i>, which attenuate FtsZ functions in response to DNA damage in other bacteria. A radiation-responsive Ser/Thr quinoprotein kinase (RqkA), characterized for its role in radiation resistance in this bacterium, could phosphorylate several cognate proteins, including FtsZ (drFtsZ) at Serine 235 (S235) and Serine 335 (S335) residues. Here, we reported the detailed characterization of S235 and S335 phosphorylation effects in the regulation of drFtsZ functions and demonstrated that the phospho-mimetic replacements of these residues in drFtsZ had grossly affected its functions that could result in cell cycle arrest in response to DNA damage in <i>D. radiodurans</i>. Interestingly, the phospho-ablative replacements were found to be nearly similar to drFtsZ, whereas the phospho-mimetic mutant lost the wild-type protein's signature characteristics, including its dynamics under normal conditions. The kinetics of post-bleaching recovery for drFtsZ and phospho-mimetic mutant were nearly similar at 2 h post-irradiation recovery but were found to be different under normal conditions. These results highlighted the role of S/T phosphorylation in the regulation of drFtsZ functions and cell cycle arrest in response to DNA damage, which is demonstrated for the first time, in any bacteria.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"5 1","pages":"27-42"},"PeriodicalIF":2.7,"publicationDate":"2022-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2022-00082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50138241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early developmental phenotypes in the cystic fibrosis sheep model","authors":"Arnaud J. Van Wettere,&nbsp;Shih-Hsing Leir,&nbsp;Calvin U. Cotton,&nbsp;Misha Regouski,&nbsp;Iuri Viotti Perisse,&nbsp;Jenny L. Kerschner,&nbsp;Alekh Paranjapye,&nbsp;Zhiqiang Fan,&nbsp;Ying Liu,&nbsp;Makayla Schacht,&nbsp;Kenneth L. White,&nbsp;Irina A. Polejaeva,&nbsp;Ann Harris","doi":"10.1096/fba.2022-00085","DOIUrl":"10.1096/fba.2022-00085","url":null,"abstract":"<p>Highly effective modulator therapies for cystic fibrosis (CF) make it a treatable condition for many people. However, although CF respiratory illness occurs after birth, other organ systems particularly in the digestive tract are damaged before birth. We use an ovine model of CF to investigate the in utero origins of CF disease since the sheep closely mirrors critical aspects of human development. Wildtype (WT) and <i>CFTR</i> ^-/- sheep tissues were collected at 50, 65, 80, 100, and 120 days of gestation and term (147 days) and used for histological, electrophysiological, and molecular analysis. Histological abnormalities are evident in <i>CFTR-/-</i> ^-/-  animals by 80 days of gestation, equivalent to 21 weeks in humans. Acinar and ductal dilation, mucus obstruction, and fibrosis are observed in the pancreas; biliary fibrosis, cholestasis, and gallbladder hypoplasia in the liver; and intestinal meconium obstruction, as seen at birth in all large animal models of CF. Concurrently, cystic fibrosis transmembrane conductance regulator (CFTR)-dependent short circuit current is present in WT tracheal epithelium by 80 days gestation and is absent from <i>CFTR</i> ^-/- tissues. Transcriptomic profiles of tracheal tissues confirm the early expression of <i>CFTR</i> and suggest that its loss does not globally impair tracheal differentiation.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"5 1","pages":"13-26"},"PeriodicalIF":2.7,"publicationDate":"2022-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/54/b9/FBA2-5-13.PMC9832529.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10535609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"“Student-led workshop strengthens perceived discussion skills and community in an interdisciplinary graduate program”","authors":"Catharine Shipps,&nbsp;Kyra L. Thrush,&nbsp;Clorice R. Reinhardt,&nbsp;Sara A. Siwiecki,&nbsp;Jennifer L. Claydon,&nbsp;Dorottya B. Noble,&nbsp;Corey S. O'Hern","doi":"10.1096/fba.2021-00165","DOIUrl":"10.1096/fba.2021-00165","url":null,"abstract":"<p>The Integrated Graduate Program in Physical and Engineering Biology (IGPPEB) at Yale University brings together Ph.D. students from the physical, engineering, and biological sciences. The main goals of this program are for students to become comfortable working in an interdisciplinary and collaborative research environment and adept at communicating with scientists and nonscientists. To fill a student-identified learning gap in engaging in inclusive discussions, IGPPEB students developed a communication workshop to improve skills in visual engagement, citing specific content, constructive conversation entrances, and encouragement of peers. Based on short- and long-term assessment of the workshop, 100% of students reported that it should be offered to future cohorts and 63% of students perceived it to be personally helpful. Additionally, 92% of participants reported using one or more of the core skills beyond the course, with skills in “Encouraging peers” and “Constructive conversation entrances” rated the highest in perceived improvement. Based on the highest average rating of 76 ± 24 (on a scale of 0–100), students agreed that the workshop made them feel more welcome in the IGPPEB community. With a rating of 68 ± 13, they also agreed that the workshop had a positive impact on their graduate school experience. Participants provided suggestions for future improvements, such as increasing student involvement in leading discussions of course material. This study demonstrates that a student-led workshop can improve perceived discussion skills and build community across an interdisciplinary program in the sciences.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"5 1","pages":"1-12"},"PeriodicalIF":2.7,"publicationDate":"2022-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2021-00165","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10535605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When women win, we all win—Call for a gendered global NCD agenda","authors":"Christine Ngaruiya","doi":"10.1096/fba.2021-00140","DOIUrl":"10.1096/fba.2021-00140","url":null,"abstract":"<p>Gender is a social determinant of health, interacting with other factors such as income, education, and housing and affects health care access and health care outcomes. This paper reviews key literature and policies on health disparities and gender disparities within health. It examines noncommunicable disease (NCD) health outcomes through a gender lens and challenges existing prevailing measures of success for NCD outcomes that focus primarily on mortality. Chronic respiratory disease, one of the four leading contributors to NCD mortality, is highlighted as a case study to demonstrate the gender gap. Women have different risk factors and higher morbidity for chronic respiratory disease compared to men but morbidity is shadowed by a penultimate research focus on mortality, which results in less attention to the gap in women's NCD outcomes. This, in turn, affects how resources, programs, and interventions are implemented. It will likely slow progress in reducing overall NCD burden if we do not address risk factors in an equitable fashion. The article closes with recommendations to address these gender gaps in NCD outcomes. At the policy level, increasing representation and inclusion in global public health leadership, prioritizing NCDs among marginalized populations by global health societies and political organizations, aligning the gendered global NCD agenda with other well-established movements will each catalyze change for gender-based disparities in global NCDs specifically. Lastly, incorporating gender-based indicators and targets in major NCD-related goals and advancing gender-based NCD research will strengthen the evidence base for women's unique NCD risks and health outcomes.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"4 12","pages":"741-757"},"PeriodicalIF":2.7,"publicationDate":"2022-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9721093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9170260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ralph A. Bradshaw: Scholar, leader, entrepreneur","authors":"Philip D. Stahl","doi":"10.1096/fba.2022-00088","DOIUrl":"10.1096/fba.2022-00088","url":null,"abstract":"&lt;p&gt;Ralph Bradshaw, sage colleague, entrepreneur, gifted editor, and prescient scientist, recently stepped down as the Editor in Chief of &lt;i&gt;FASEB BioAdvances&lt;/i&gt;. This presents the opportunity to pause and reflect on the career of an extraordinary individual, whose continuing commitment to science, science publishing, and the scholarly societies that represent and advocate for us all, illustrates the exceptional. Ralph's career reflects an unyielding dedication to those goals that we all strive to achieve—scholarship with high standards, leadership, service, and entrepreneurship.&lt;/p&gt;&lt;p&gt;Ralph grew up in the Boston area and attended Colby College, where he majored in chemistry; he completed his doctorate with Robert Hill in the Biochemistry Department at Duke, where his thesis work focused on protein chemistry. His postdoctoral work at Indiana University in the laboratory of Frank Gurd and the University of Washington in the laboratory of Hans Neurath allowed him to refine his repertoire of protein sequencing and analytic methodologies. P. Roy Vagelos (former CEO of Merck and former department head at Washington University) recruited Ralph to the Department of Biological Chemistry at Washington University as Roy began a highly successful renovation and rebuilding of the department after the long reign of Carl Cori. This is where I first met Ralph, as we were newly appointed assistant professors in biochemistry and physiology, respectively, and shared our interest in graduate education.&lt;/p&gt;&lt;p&gt;In 1973, Vagelos and colleagues at Washington University advanced a novel approach to graduate education in the biological and biomedical sciences, the Division of Biology and Biomedical Sciences (DBBS)—recently named the Roy and Diana Vagelos Division of Biology and Biomedical Sciences. The idea was based on the ongoing diversification of medical and biological research, where the traditional departmental boundaries that separated disparate “fields of research” were increasingly seen as hardened silos that suppressed innovation and reduced opportunities for graduate research. By creating programs built on common faculty interests rather than departmental affiliation, cross disciplinary opportunities for graduate research flourished—this approach in one form or another is now common among nearly all research institutions. Ralph Bradshaw played a key role in getting the DBBS off the ground—perhaps a precursor to his now well appreciated organizational skills. He was appointed the first chair of the newly formed graduate admissions committee, an enthusiastic recruiter of talented students to the programs and the principal investigator on one of the first NIH training grants under this new umbrella. Roy Vagelos commented, “Bradshaw was an enthusiastic and very effective recruiter of graduate students to Washington University. When the DBBS faculty decided that the University should have greater diversity among its graduate students, Ralph led a small group of facu","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"4 11","pages":"691-693"},"PeriodicalIF":2.7,"publicationDate":"2022-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9635006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40673514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone marrow-derived extracellular vesicles modulate the abundance of infiltrating immune cells in the brain and exert an antiviral effect against the Japanese encephalitis virus","authors":"Naina Soni,&nbsp;Aarti Tripathi,&nbsp;Sriparna Mukherjee,&nbsp;Suchi Gupta,&nbsp;Sujata Mohanty,&nbsp;Anirban Basu,&nbsp;Arup Banerjee","doi":"10.1096/fba.2022-00071","DOIUrl":"10.1096/fba.2022-00071","url":null,"abstract":"<p>Mesenchymal stem cells (MSCs) have regenerative capacity and have reported a beneficial effect on the Japanese encephalitis virus (JEV) in an encephalitis model. However, the MSCs do not cross the blood–brain barrier and have other disadvantages limiting their therapeutic utility scope. Recently, there has been a shift in concept from a cell-based to a cell-free approach using MSCs-derived extracellular vesicles (MSC-EVs). The MSC-EVs retain regenerative and immunomodulatory capacity as their parental cells. However, the role of MSC-EVs in limiting JEV pathology remains elusive. In this study, we have used Bone marrow (BM)-derived EV (BM-EVs) and assessed their effect on JEV replication and pathogenesis in primary neuronal stem cells and a murine model. The in vitro and in vivo studies suggested that BM-derived EVs delay JEV-induced symptoms and death in mice, improve the length of survival, accelerate neurogenesis in primary neuronal stem cells, reduce JEV-induced neuronal death, and attenuate viral replication. BM-EVs treatment upregulated interferon-stimulated genes. Flow cytometry analysis revealed a reduction in the frequency of macrophages. At the same time, CD4+ T cells and neutrophils were significantly augmented, accompanied by the alteration of cytokine expression with the administration of BM-EVs, reinforcing the immunomodulatory role of EVs during JEV-induced encephalitis. In conclusion, our study describes the beneficial role of BM-EVs in limiting JEV pathology by attenuating virus replication, enhancing antiviral response, and neurogenesis in primary neuronal stem cells. However, BM-EVs do not seem to protect BBB integrity and alter immune cell infiltration into the treated brain.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"4 12","pages":"798-815"},"PeriodicalIF":2.7,"publicationDate":"2022-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9721092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10433263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic regulation of the transcriptome and proteome of the equine embryo during maternal recognition of pregnancy","authors":"Alba Rudolf Vegas,&nbsp;Giorgia Podico,&nbsp;Igor F. Canisso,&nbsp;Heinrich Bollwein,&nbsp;Thomas Fröhlich,&nbsp;Stefan Bauersachs,&nbsp;Carmen Almiñana","doi":"10.1096/fba.2022-00063","DOIUrl":"10.1096/fba.2022-00063","url":null,"abstract":"<p>During initial maternal recognition of pregnancy (MRP), the equine embryo displays a series of unique events characterized by rapid blastocyst expansion, secretion of a diverse array of molecules, and transuterine migration to interact with the uterine surface. Up to date, the intricate transcriptome and proteome changes of the embryo underlying these events have not been critically studied in horses. Thus, the objective of this study was to perform an integrative transcriptomic (including mRNA, miRNAs, and other small non-coding RNAs) and proteomic analysis of embryos collected from days 10 to 13 of gestation. The results revealed dynamic transcriptome profiles with a total of 1311 differentially expressed genes, including 18 microRNAs (miRNAs). Two main profiles for mRNAs and miRNAs were identified, one with higher expression in embryos ≤5 mm and the second with higher expression in embryos ≥7 mm. At the protein level, similar results were obtained, with 259 differentially abundant proteins between small and large embryos. Overall, the findings demonstrated fine-tuned transcriptomic and proteomic regulations in the developing embryo associated with embryo growth. The identification of specific regulation of mRNAs, proteins, and miRNAs on days 12 and 13 of gestation suggested these molecules as pivotal for embryo development and as involved in MRP, and in establishment of pregnancy in general. In addition, the results revealed new insights into prostaglandin synthesis by the equine embryo, miRNAs and genes potentially involved in modulation of the maternal immune response, regulation of endometrial receptivity and of late implantation in the mare.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"4 12","pages":"775-797"},"PeriodicalIF":2.7,"publicationDate":"2022-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9721094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10433264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}