{"title":"Commentary on \"Application of Photoshop-based Image Analysis to Quantification of Hormone Receptor Expression in Breast Cancer\".","authors":"Allen M Gown","doi":"10.1369/00221554221145227","DOIUrl":"10.1369/00221554221145227","url":null,"abstract":"At the time of publication of this article, image analysis as applied to diagnostic surgical pathology was a nascent technology, often characterized as a “solution in search of a problem.” After all, biomarkers such as estrogen receptor (ER) in breast cancer were scored in a threshold manner, with the assumption that this scoring was highly accurate and reproducible. Unfortunately, several studies in the early 2000s found significant discordance in this ER evaluation when slides were re-reviewed.1,2 Ironically, prior approaches to determining ER expression in breast cancer, for example, the dextran-coated charcoal method, were quantifiable and reproducible, but required fresh frozen tissue and could not be used on formalin-fixed paraffin-embedded tissue. Image analysis on deparaffinized, formalin-fixed tissue sections immunostained with appropriate antibodies was anticipated to be a method that could increase the predictive power of IHC determination of hormone receptor status. Indeed, this 1997 paper was one of the first to employ image analysis in the evaluation of ER. While after more than two decades Photoshop has maintained its role as a premier raster graphics and digital art editor, it has not taken a second life as an image analysis tool. We selected Photoshop as a “maverick” technique that permitted us to accomplish the analysis we desired, but to also avoid the use of commercial image analysis instruments and software, which at that time were expensive and unaffordable for our laboratory. Today, while commercial image analysis hardware and software are legion, free public domain software such as QuPath can yield comparable results as many commercial software packages3 and far exceed the capabilities of Photoshop. While our 1997 paper succeeded as a “proof of principle,” now 25 years later, ER is still not quantified in the vast majority of cases, but is instead still “eyeballed” to determine whether more than 1% of tumor cells are positive for nuclear signal (or between 1% and 10%), but no image analysis–based quantification is required.4 There may still be a role in the future for more quantitative ER determination in breast cancer, but that will be determined not by technology alone but largely by evidence that may be forthcoming from clinical studies. But it will almost certainly not involve the use of Photoshop!","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":"70 11-12","pages":"767-768"},"PeriodicalIF":3.2,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9903209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9280808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Long Hanging Structure of Collagen VII Connects the Elastic Fibers and the Basement Membrane in Young Skin Tissue.","authors":"Takeshi Tohgasaki, Shino Nishizawa, Shinya Kondo, Shioji Ishiwatari, Tetsuhito Sakurai","doi":"10.1369/00221554221145998","DOIUrl":"10.1369/00221554221145998","url":null,"abstract":"<p><p>Aging leads to substantial structural changes in the skin. Elastic fibers maintain skin structure, but their degeneration and loss of function with age result in wrinkle formation and loss of skin elasticity. Oxytalan fiber, a type of elastic fiber, extends close to the dermal-epidermal junction (DEJ) from the back of the dermis. Oxytalan fibers are abundant in the papillary layer and contribute to skin elasticity and texture. However, to accurately understand the mechanisms of skin elasticity, the interaction between elastic fibers and DEJ should be elucidated. Here, we investigated elastic fibers and DEJ and their structural alterations with aging. Several basement membrane proteins [collagen (COL) IV, COLVII, and laminin 332], fibrous tropoelastin, and fibrillin-1 in excised human skin tissue were observed using three-dimensional imaging. Age-related alterations in COLVII, elastic fibers, and fibrillin-1 were evaluated. We found that COLVII forms long hanging structures and is co-localized with fibrous tropoelastin in young skin but not aged skin. Fibrillin-1-rich regions were observed at the tips of elastin fibers in young skin tissue, but rarely in aged skin. This co-localization of elastic fiber and COLVII may maintain skin structure, thereby preventing wrinkling and sagging. COLVII is a potential therapeutic target for skin wrinkling.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":"70 11-12","pages":"751-757"},"PeriodicalIF":3.2,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9903210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10710505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Aberrant Expression of Thymosin Beta-4 Correlates With Advanced Disease and BRAF V600E Mutation in Thyroid Cancer.","authors":"Chi-Yu Kuo, Jie-Yang Jhuang, Wen-Chien Huang, Shih-Ping Cheng","doi":"10.1369/00221554221138370","DOIUrl":"10.1369/00221554221138370","url":null,"abstract":"<p><p>Thymosin beta-4 (TMSB4X) was recently identified as a differentially expressed gene between malignant and non-malignant thyroid cells via single-cell RNA sequencing. In the present study, we aimed to study the immunostaining pattern of TMSB4X in benign and malignant thyroid neoplasms. Immunohistochemical analysis revealed that normal thyroid tissue or benign thyroid disorders exhibited undetectable immunoreactivity against TMSB4X except for positive staining of inflammatory infiltrates and stromal cells associated with autoimmune thyroid disease. By contrast, overexpression of TMSB4X was observed in a variety of thyroid malignancies, including papillary, follicular, poorly differentiated, and undifferentiated thyroid cancer. Among 141 patients with differentiated thyroid cancer, higher TMSB4X expression was associated with papillary tumor type, extrathyroidal extension, lymph node metastasis, and BRAF V600E mutation. The results were consistent with those from the public transcriptomic datasets. In summary, TMSB4X expression was aberrantly increased in various types of thyroid cancer, and higher TMSB4X expression was correlated with advanced disease characteristics. Thymosin beta-4 may be a novel downstream effector of the BRAF V600E mutation.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":"70 10","pages":"707-716"},"PeriodicalIF":3.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9660367/pdf/10.1369_00221554221138370.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10635856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Donald J Johann, Ik Jae Shin, Adam Roberge, Sarah Laun, Erich A Peterson, Meei Liu, Matthew A Steliga, Jason Muesse, Michael R Emmert-Buck, Michael A Tangrea
{"title":"Effect of Antigen Retrieval on Genomic DNA From Immunodissected Samples.","authors":"Donald J Johann, Ik Jae Shin, Adam Roberge, Sarah Laun, Erich A Peterson, Meei Liu, Matthew A Steliga, Jason Muesse, Michael R Emmert-Buck, Michael A Tangrea","doi":"10.1369/00221554221124163","DOIUrl":"https://doi.org/10.1369/00221554221124163","url":null,"abstract":"<p><p>Immunohistochemical (IHC) staining is an established technique for visualizing proteins in tissue sections for research studies and clinical applications. IHC is increasingly used as a targeting strategy for procurement of labeled cells via tissue microdissection, including immunodissection, computer-aided laser dissection (CALD), expression microdissection (xMD), and other techniques. The initial antigen retrieval (AR) process increases epitope availability and improves staining characteristics; however, the procedure can damage DNA. To better understand the effects of AR on DNA quality and quantity in immunodissected samples, both clinical specimens (<i>KRAS</i> gene mutation positive cases) and model system samples (lung cancer patient-derived xenograft tissue) were subjected to commonly employed AR methods (heat induced epitope retrieval [HIER], protease digestion) and the effects on DNA were assessed by Qubit, fragment analysis, quantitative PCR, digital droplet PCR (ddPCR), library preparation, and targeted sequencing. The data showed that HIER resulted in optimal IHC staining characteristics, but induced significant damage to DNA, producing extensive fragmentation and decreased overall yields. However, neither of the AR methods combined with IHC prevented ddPCR amplification of small amplicons and gene mutations were successfully identified from immunodissected clinical samples. The results indicate for the first time that DNA recovered from immunostained slides after standard AR and IHC processing can be successfully employed for genomic mutation analysis via ddPCR and next-generation sequencing (NGS) short-read methods.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":"70 9","pages":"643-658"},"PeriodicalIF":3.2,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9527476/pdf/10.1369_00221554221124163.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10134250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Denis Depes, Ari Mennander, Rauha Vehniäinen, Timo Paavonen, Ivana Kholová
{"title":"Human Pulmonary Vein Myocardial Sleeve Autonomic Neural Density and Cardiovascular Mortality.","authors":"Denis Depes, Ari Mennander, Rauha Vehniäinen, Timo Paavonen, Ivana Kholová","doi":"10.1369/00221554221129899","DOIUrl":"https://doi.org/10.1369/00221554221129899","url":null,"abstract":"<p><p>Myocardial sleeves around pulmonary veins (PVs) are highly innervated structures with heterogeneous morphological and electrophysiological characteristics. Autonomic nerve dysfunction in the myocardium may be associated with an increased risk of cardiovascular morbidity and mortality. This article studied autonomic neural remodeling in myocardial sleeves around PVs and atrial-PV ostia with immunohistochemical and morphometric methods with clinicopathological correlations. PVs were collected from 37 and atrial-PV ostia from 17 human autopsy hearts. Immunohistochemical analysis was performed using antibodies against tyrosine hydroxylase (TH), choline acetyltransferase (CHAT), and growth-associated protein 43 (GAP43). In the PV cohort, subjects with immediate cardiovascular cause of death had significantly decreased sympathetic nerve density in fibro-fatty tissue vs those with non-cardiovascular cause of death (1624.53 vs 2522.05 µm<sup>2</sup>/mm<sup>2</sup>, <i>p</i>=0.038). In the atrial-PV ostia cohort, parasympathetic nerve density in myocardial sleeves was significantly increased in subjects with underlying cardiovascular cause of death (19.48 µm<sup>2</sup>/mm<sup>2</sup>) than subjects with underlying non-cardiovascular cause of death with no parasympathetic nerves detected (<i>p</i>=0.034). Neural growth regionally varied in sympathetic nerves and was present in most of the parasympathetic nerves. Heterogeneous autonomic nerve distribution and growth around PVs and atrial-PV ostia might play a role in cardiovascular morbidity and mortality. No association in nerve density was found with atrial fibrillation.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":"70 9","pages":"627-642"},"PeriodicalIF":3.2,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9527475/pdf/10.1369_00221554221129899.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10124337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Spatially Resolved and Highly Multiplexed Protein and RNA In Situ Detection by Combining CODEX With RNAscope In Situ Hybridization.","authors":"Yilun Cheng, Rachel K Burrack, Qingsheng Li","doi":"10.1369/00221554221114174","DOIUrl":"https://doi.org/10.1369/00221554221114174","url":null,"abstract":"<p><p>Highly multiplexed protein and RNA in situ detection on a single tissue section concurrently is highly desirable for both basic and applied biomedical research. CO-detection by inDEXing (CODEX) is a new and powerful platform to visualize up to 60 protein biomarkers in situ, and RNAscope in situ hybridization (RNAscope) is a novel RNA detection system with high sensitivity and unprecedent specificity at a single-cell level. Nevertheless, to our knowledge, the combination of CODEX and RNAscope remained unreported until this study. Here, we report a simple and reproducible combination of CODEX and RNAscope. We also determined the cross-reactivities of CODEX anti-human antibodies to rhesus macaques, a widely used animal model of human disease.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":"70 8","pages":"571-581"},"PeriodicalIF":3.2,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9393509/pdf/10.1369_00221554221114174.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9914518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rapid Histological Assessment of Prostate Specimens in the Three-dimensional Space by Hydrophilic Tissue Clearing and Confocal Microscopy.","authors":"Yu-Ching Peng, Yu-Chieh Lin, Yu-Ling Hung, Chien-Chung Fu, Margaret Dah-Tsyr Chang, Yen-Yin Lin, Teh-Ying Chou","doi":"10.1369/00221554221116936","DOIUrl":"https://doi.org/10.1369/00221554221116936","url":null,"abstract":"<p><p>Microscopic examination of biopsied and resected prostatic specimens is the mainstay in the diagnosis of prostate cancer. However, conventional analysis of hematoxylin and eosin (H&E)-stained tissue is time-consuming and offers limited two-dimensional (2D) information. In the current study, we devised a method-termed <u>P</u>rostate <u>R</u>apid <u>O</u>ptical examination for cancer <u>STAT</u>us (proSTAT)-for rapid screening of prostate cancer using high-resolution 2D and three-dimensional (3D) confocal images obtained after hydrophilic tissue clearing of 100-µm-thick tissue slices. The results of the proSTAT method were compared with those of traditional H&E stains for the analysis of cores (<i>n</i>=15) obtained from radical prostatectomy specimens (<i>n</i>=5). Gland lumen formation, consistent with Gleason pattern 3, was evident following tracking of multiple optical imaging sections. In addition, 3D rendering allowed visualizing a tubular network of interconnecting branches. Rapid 3D fluorescent labeling of tumor protein p63 accurately distinguished prostate adenocarcinoma from normal tissue and benign lesions. Compared with conventional stains, the 3D spatial and molecular information extracted from proSTAT may significantly increase the amount of available data for pathological assessment of prostate specimens. Our approach is amenable to automation and-subject to independent validation-can find a wide spectrum of clinical and research applications.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":"70 8","pages":"597-608"},"PeriodicalIF":3.2,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9393508/pdf/10.1369_00221554221116936.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9914782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Suad A K Shamis, Jean Quinn, Elizabeth E A Mallon, Joanne Edwards, Donald C McMillan
{"title":"The Relationship Between the Tumor Cell Expression of Hypoxic Markers and Survival in Patients With ER-positive Invasive Ductal Breast Cancer.","authors":"Suad A K Shamis, Jean Quinn, Elizabeth E A Mallon, Joanne Edwards, Donald C McMillan","doi":"10.1369/00221554221110280","DOIUrl":"https://doi.org/10.1369/00221554221110280","url":null,"abstract":"<p><p>The prognostic significance of hypoxia markers, hypoxia-inducible factor-1α (HIF-1α), hypoxia-inducible factor-2α (HIF-2α), and carbonic anhydrase IX (CAIX), was investigated in estrogen receptor (ER)-positive breast cancer patients. Immunohistochemistry determined the expression of makers in two independent ductal ER-positive cohorts (Training set, <i>n</i>=373 and Validation set, <i>n</i>=285) and was related to clinicopathological parameters and disease-free survival (DFS). In the training cohort, nuclear HIF-1α (1) was independently associated with poorer DFS in luminal A tumors [hazard ratio (HR) = 0.53 95% confidence interval (CI): 0.30-0.94, <i>p</i>=0.030]. In the validation cohort, both HIF-1α (1) and CAIX were independently associated with decreased DFS in the entire cohort (HR = 1.85 95% CI: 1.10-3.11, <i>p</i>=0.019; HR = 1.74 95% CI: 1.08-2.82, <i>p</i>=0.023), in luminal A disease (HR = 1.98 95% CI: 1.02-3.83, <i>p</i>=0.042), and in luminal B disease (HR = 2.75 95% CI: 1.66-4.55, <i>p</i><0.001), respectively. Taken together, elevated cytoplasmic HIF-1α (1) expression was an independent prognostic factor in luminal A disease, whereas CAIX was an independent prognostic factor in luminal B disease. Further work in large tissue cohorts is required.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":" ","pages":"479-494"},"PeriodicalIF":3.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ab/a4/10.1369_00221554221110280.PMC9284237.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40563635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Morphology of Schwann Cell Processes Supports Renal Sympathetic Nerve Terminals With Local Distribution of Adrenoceptors.","authors":"Seishi Maeda, Yusuke Minato, Sachi Kuwahara-Otani, Hiroki Yamanaka, Mitsuyo Maeda, Yosky Kataoka, Hideshi Yagi","doi":"10.1369/00221554221106812","DOIUrl":"https://doi.org/10.1369/00221554221106812","url":null,"abstract":"<p><p>Nerves in the renal parenchyma comprise sympathetic nerves that act on renal arteries and tubules to decrease blood flow and increase primary urine reabsorption, respectively. Synaptic vesicles release neurotransmitters that activate their effector tissues. However, the mechanisms by which neurotransmitters exert individual responses to renal effector cells remain unknown. Here, we investigated the spatial and molecular compositional associations of renal Schwann cells (SC) supporting the nerve terminals in male rats. The nerve terminals of vascular smooth muscle cells (SMCs) enclosed by renal SC processes were exposed through windows facing the effectors with presynaptic specializations. We found that the adrenergic receptors (ARs) α2A, α2C, and β2 were localized in the SMC and the basal side of the tubules, where the nerve terminals were attached, whereas the other subtypes of ARs were distributed in the glomerular and luminal side, where the norepinephrine released from nerve endings may have indirect access to ARs. In addition, integrins α4 and β1 were coexpressed in the nerve terminals. Thus, renal nerve terminals could contact their effectors via integrins and may have a structure, covered by SC processes, suitable for intensive and directional release of neurotransmitters into the blood, rather than specialized structures in the postsynaptic region.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":"70 7","pages":"495-513"},"PeriodicalIF":3.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284235/pdf/10.1369_00221554221106812.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9786760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Madhulika B Gupta, Kyle K Biggar, Cun Li, Peter W Nathanielsz, Thomas Jansson
{"title":"Increased Colocalization and Interaction Between Decidual Protein Kinase A and Insulin-like Growth Factor-Binding Protein-1 in Intrauterine Growth Restriction.","authors":"Madhulika B Gupta, Kyle K Biggar, Cun Li, Peter W Nathanielsz, Thomas Jansson","doi":"10.1369/00221554221112702","DOIUrl":"https://doi.org/10.1369/00221554221112702","url":null,"abstract":"<p><p>Increased phosphorylation of decidual insulin-like growth factor-binding protein-1 (IGFBP-1) can contribute to intrauterine growth restriction (IUGR) by decreasing the bioavailability of insulin-like growth factor-1 (IGF-1). However, the molecular mechanisms regulating IGFBP-1 phosphorylation at the maternal-fetal interface are poorly understood. Protein kinase A (PKA) is required for normal decidualization. Consensus sequences for PKA are present in IGFBP-1. We hypothesized that the expression/interaction of PKA with decidual IGFBP-1 is increased in IUGR. Parallel reaction monitoring-mass spectrometry (PRM-MS) identified multiple PKA peptides (<i>n</i>=>30) co-immunoprecipitating with IGFBP-1 in decidualized primary human endometrial stromal cells (HESC). PRM-MS also detected active PKA<sup>pThr197</sup> and greater site-specific IGFBP-1 phosphorylation<sup>(pSer119), (pSer98+pSer101) (pSer169+pSer174)</sup> in response to hypoxia. Hypoxia promoted colocalization [dual immunofluorescence (IF)] of PKA with IGFBP-1 in decidualized HESC. Colocalization (IF) and interaction (proximity ligation assay) of PKA and IGFBP-1 were increased in decidua collected from placenta of human IUGR pregnancies (<i>n</i>=8) compared with decidua from pregnancies with normal fetal growth. Similar changes were detected in decidual PKA/IGFBP-1 using placenta from baboons subjected to maternal nutrient reduction (MNR) vs controls (<i>n</i>=3 each). In baboons, these effects were evident in MNR at gestational day 120 prior to IUGR onset. Increased PKA-mediated phosphorylation of decidual IGFBP-1 may contribute to decreased IGF-1 bioavailability in the maternal-fetal interface in IUGR.</p>","PeriodicalId":16079,"journal":{"name":"Journal of Histochemistry & Cytochemistry","volume":"70 7","pages":"515-530"},"PeriodicalIF":3.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284236/pdf/10.1369_00221554221112702.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10091267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}