Cells Tissues Organs最新文献

{"title":"Function of Transforming Growth Factor β2 and β3 in Palatogenesis.","authors":"Miwaki Aoki, Akira Nakajima, Nichika Fukumashi, Risako Okuma, Mitsuru Motoyoshi, Charles F Shuler","doi":"10.1159/000544097","DOIUrl":"https://doi.org/10.1159/000544097","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to examine the transforming growth factor (TGF)-β signaling pathway during secondary palate fusion by transfecting single and double small interfering RNA (siRNAs) for TGF-β2 and -β3. This investigation also focused on understanding the phenotype of palatal development.</p><p><strong>Methods: </strong>siRNAs targeting TGF-β2 and -β3 were used in an organ culture model of fusion of the secondary palate of 13-day embryonic ICR mice cultured for up to 72 h. The palatal shelves were collected at different times following the initiation of organ culture and were examined for TGF-β2 and -β3 gene expression. Downstream signaling was characterized using Western blotting and PCR.</p><p><strong>Results: </strong>In the double siRNA-treated palatal shelves, approximately 90% (91% anterior, 89% posterior with phenotype A) showed fusion failure in hematoxylin and eosin staining. Phosphorylation of Smad-dependent and -independent signaling showed a significant reduction in phosphorylation in double knockdown palate organ cultures when compared to single knockdown cultures. Although, the expression of matrix metalloproteinase 13 and TIMP2 were small influenced by siTGF-β2, the extracellular matrix and transcription factor expressions showed to be significantly reduced in double knockdown palate compared to single knockdown palates.</p><p><strong>Conclusions: </strong>This study demonstrates that double siRNAs targeting TGF-β2 and -β3 results in phenotypes during secondary palatal fusion and that they could be affected phosphorylation of Smad-dependent and -independent signaling synergistically compared to single knockdown of TGF-β2 and -β3. The results of this study demonstrate important functions during secondary palatal fusion and will contribute to our understanding of the etiology of cleft palate.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-15"},"PeriodicalIF":2.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hindlimb unloading reversibly attenuates osteogenic potential of rat skeletal stem and progenitor cells ex vivo.","authors":"Elena Markina, Elena Andreeva, Ludmila Buravkova","doi":"10.1159/000545284","DOIUrl":"https://doi.org/10.1159/000545284","url":null,"abstract":"<p><strong>Introduction: </strong>Prolonged space flights negatively affect skeleton. Stromal cells of mesenchymal origin play a crucial role in maintaining homeostasis and in regulating the physiological remodeling of various tissues, and this has particular significance for bone.</p><p><strong>Methods: </strong>Hindlimb unloading (HU) of rats as a ground-based model for simulation of microgravity was implemented. The functional activity of skeletal stem and progenitor cells (SSPCs) from rat femoral bones was assessed in vitro after 2 weeks of HU and after 2 weeks of subsequent recovery of load support (HU+R). To characterize the growth of the SSPCs, the number of population doublings (PD) was calculated. Histochemical detection of the activity of alkaline phosphatase (AP) - an early marker of osteo-differentiation - on day 7, and of extracellular matrix (ECM) mineralization - as a sign of late osteo-differentiation - on day 21, were carried out. Quantitative real-time PCR was performed to detect the expression of the genes encoding proteins associated with the functional activity of osteoprogenitor cells (Pparg, Runx2, Alpl, Cxcl12) and bone tissue homeostasis (Mmp9, Spp1, RANKL, OPG, Ibsp, BMP10, Sost).</p><p><strong>Results: </strong>After HU, a decrease in AP activity and a significant attenuation of extracellular matrix mineralization were detected. There was also significant downregulation of the genes those for bone matrix proteins (RANKL, OPG, Ibsp), and of the master-genes controlling osteo- and adipo-differentiation (Runx2, Alpl), as well as of Mmp9, encoding a regulatory molecule of bone matrix remodeling. By contrast, sclerostin (Sost) was upregulated. After HU+R, the PD, an AP activity and the level of extracellular matrix mineralization were restored.</p><p><strong>Conclusions: </strong>HU leads to inhibition of the osteoplastic function of SSPCs. The presented data are significant for the elucidation of microgravity-induced mechanisms of bone impairment and for the development of countermeasures for astronauts as well as for osteo-deficient patients after prolonged immobilization.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-20"},"PeriodicalIF":2.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paper-based Microfluidics for Tissue Engineering and Regenerative Medicine.","authors":"Jaehun Lee, Haoyue Luo, Yun-Ya Chen, Kirsten Ilestad, Dottie Yu, Mikayla Ybarra, Chao Ma","doi":"10.1159/000545248","DOIUrl":"https://doi.org/10.1159/000545248","url":null,"abstract":"<p><strong>Background: </strong>Paper-based microfluidics have gained significant attention as cost-effective and biocompatible platforms for various biological and medical applications. These devices facilitate the replication of complex tissue environments and offer a versatile alternative to traditional microfluidic systems.</p><p><strong>Summary: </strong>This review highlights recent advances in paper-based microfluidics for tissue engineering and regenerative medicine. Key applications include 3D cell culture, bioanalysis assays, and high-throughput screening systems. Innovations in fabrication methods, such as wax printing and inkjet printing, have enhanced the functionality and scalability of these devices. Furthermore, the integration of biomaterials and surface modification techniques has improved their utility in replicating physiological conditions and studying cellular behaviors. Challenges such as mechanical robustness, imaging compatibility, and immune antigenicity are also addressed, alongside potential solutions and future directions.</p><p><strong>Key messages: </strong>Paper-based microfluidic systems provide a transformative platform for tissue engineering and regenerative medicine, offering simplicity, affordability, and functional versatility. With ongoing innovations, these devices are poised to bridge the gap between laboratory research and clinical applications, supporting advancements in personalized medicine, regenerative therapies, and disease modeling.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-23"},"PeriodicalIF":2.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements and Challenges in Tracheal Epithelium Regeneration: Insights into Tissue Engineering Approaches.","authors":"Dina Gadalla, Maeve M Kennedy, David G Lott","doi":"10.1159/000545132","DOIUrl":"https://doi.org/10.1159/000545132","url":null,"abstract":"<p><p>Background The trachea, a vital conduit in the lower airway system, can be affected by various disorders, such as tracheal neoplasms and tracheoesophageal fistulas, that often necessitate reconstruction. While short-segment defects can sometimes be addressed with end-to-end anastomosis, larger defects require tracheal reconstruction, a complex procedure with no universally successful replacement strategy. Tissue engineering offers a promising solution for tracheal repair, particularly focusing on regenerating its epithelium, which plays a critical role in protecting the respiratory system and facilitating mucociliary clearance. However, replicating the complex structure and functionality of the tracheal epithelium remains a significant challenge, with key hurdles including proper cell differentiation, functional mucociliary clearance, and addressing the relative lack of vascular supply to the trachea. Summary Current tissue engineering approaches, including biomaterial scaffolds, decellularized tissues, and scaffold-free methods, have shown varying levels of success, while in vitro air-liquid interface (ALI) cultures have provided valuable insights into epithelial modeling. Despite these advances, translating these findings into effective in vivo applications remains difficult due to challenges such as immune responses, inadequate integration with host tissue, and limited longterm functionality of engineered constructs. Overcoming these barriers requires further refinement of cell sources, scaffold materials and bioactive factors that promote vascularization and sustained epithelial function. Key Messages This review evaluates the current strategies and modeling, biomaterial scaffolds, cells, and bioactive factors used in tracheal epithelium regeneration, as well as the methods employed to assess their success through histological, functional, and molecular analyses. While significant progress has been made, the development of a safe, functional, and clinically viable tracheal graft remains elusive, underscoring the need for continued innovation in airway tissue engineering. Future advancements in biomaterial design, stem cell technology, and bioreactor-based tissue maturation hold promise for addressing challenges.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-32"},"PeriodicalIF":2.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of corticosteroid-induced myopathy through Filgrastim induced endogenous stem cells mobilization in male albino rats.","authors":"Tarek Hamdy Abd-Elhamid, Nahla Shahat Ismail, Yahia A Amin, Fatma Y Meligy, Ahmed Talat Galal, Hoda Ahmed M Abdel-Ziz, Maha Abd-El Baki Ahmed","doi":"10.1159/000545172","DOIUrl":"https://doi.org/10.1159/000545172","url":null,"abstract":"<p><strong>Introduction: </strong>One of well-known exogenous fluorinated glucocorticoid that is used to treat inflammatory and various autoimmune illnesses is dexamethasone. Dexamethasone is known to cause skeletal muscular weakness and when used for an extended period of time, skeletal muscle undergoes atrophy. Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein that helps mobilize stem cells from bone marrow into peripheral circulation. In order to maintain the function of skeletal muscle, these mobilized stem cells multiply and differentiate into mature myocytes. This study was conducted to investigate to what extent administration of filgrastim, human methionyl granulocyte colony-stimulating factor (G-CSF), ameliorates glucocorticoid-induced skeletal muscles damage in adult male albino rats.</p><p><strong>Methods: </strong>Thirty adult male albino rats were randomly divided into three groups (ten/group), group I (control group, CG): rats received normal diet and orally given normal saline, group II (dexamethasone group, DG): rats were given dexamethasone at a dose of 0.5mg/kg for one month by intraperitoneal injection, group III (filgrastim group, FG): rats were given dexamethasone at dose of 0.5 mg/kg and on day 15, at the beginning of the third week, they were given Filgrastim at a dose of 20 µg/kg till the end of the 4th week by intraperitoneal injection with dexamethasone. Assessment of CK levels, total body weight and motor activity at different time points were done and skeletal muscles specimens were processed for light microscopy, electron microscopy and immunohistochemistry examination.</p><p><strong>Results: </strong>Administration of dexamethasone (group II) showed variant types of pathological changes such as elevated CK, decrease in body weight, impairment of muscle activity and histologically myofibrillar disarrangement together with cellular infiltration and edema. Filgrastim group showed significant reduction in most of those manifestations. Administration of filgrastim with dexamethasone meliorated most of the symptoms related to dexamethasone induced-myopathy.</p><p><strong>Conclusion: </strong>Filgrastim administration recovered manifestations of skeletal muscle injuries caused by dexamethasone.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-36"},"PeriodicalIF":2.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Downregulation of Signal Transducer and Activator of Transcription 4 (STAT4) contributes to impaired osteogenic differentiation of human bone marrow stem cells (hBMSCs) during in vitro expansion.","authors":"Weiqiong Rong, Yuanying Yuan, Shaomian Yao","doi":"10.1159/000544952","DOIUrl":"https://doi.org/10.1159/000544952","url":null,"abstract":"<p><strong>Introduction: </strong>In vitro expansion of primary human bone marrow stem cells (hBMSCs) is necessary to obtain sufficient cells for therapeutic uses. Unfortunately, hBMSCs rapidly lose their osteogenic differentiation potential during expansion, significantly limiting their applications. Signal transducer and activator of transcription 4 (STAT4) is known to play roles in cell migration, proliferation, and differentiation. This study aims to determine the expression and the role of STAT4 during the expansion of hBMSCs.</p><p><strong>Methods: </strong>STAT4 expression in different passages of hBMSCs was evaluated using qRT-PCR and Western blotting. RNA interference and adeno-associated virus serotype 2 (AAV2)-mediated gene overexpression were employed to assess the function of STAT4. RNA samples from STAT4-overexpressing hBMSCs were analyzed by RNA-seq to identify differentially expressed genes (DEGs), followed by bioinformatics analyses to determine the pathways affected by STAT4.</p><p><strong>Results: </strong>STAT4 expression progressively decreases during the in vitro expansion of hBMSCs, concomitant with the loss of osteogenic differentiation potential. STAT4 knockdown in early passage hBMSCs significantly inhibits their osteogenic differentiation, evidenced by markedly reduced calcium deposition and downregulation of osteogenic markers. STAT4 knockdown also reduces hBMSCs' proliferation ability. Conversely, STAT4 overexpression notably increases calcium deposition in passage 3 to passage 7 cells, suggesting that enhanced STAT4 expression can mitigate the loss of osteogenic potential during hBMSC expansion. Transcriptomic analysis revealed DEGs in STAT4-overexpressing hBMSCs. Subsequent bioinformatics analyses indicated that some of these DEGs are involved in pathways regulating cell differentiation and senescence.</p><p><strong>Conclusion: </strong>The in vitro expansion of hBMSCs leads to the downregulation of STAT4, which contributes to the impairment of their osteogenic potential and may affect cell self-renewability. This study provides insight into the molecular mechanisms underlying the loss of osteogenic differentiation during hBMSC expansion and identifies STAT4 as a potential target for hBMSC-based bone regeneration therapies.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-21"},"PeriodicalIF":2.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyaluronic Acid Binding Peptide Regulates Extracellular Matrix Deposition And Diminishes Fibroblast Contractility.","authors":"Beth Blake, Whitney Ann Ponwith, Klaus Rischka, Martin Wiesing, Tugba Ozdemir","doi":"10.1159/000544881","DOIUrl":"https://doi.org/10.1159/000544881","url":null,"abstract":"<p><p>Fibroblasts are central to variety of homeostatic events such as wound healing and tissue regeneration. However, their pathologic activation is thought to play roles in a variety of diseases not only limited to fibrosis, foreign body reaction, scleroderma but also cancer metastasis. Biophysical properties of the extracellular matrix (ECM) deposited by an activated fibroblast determine whether there is a pro-regenerative or scarring response. Compared to aged fibroblasts, embryonic fibroblasts were shown to deposit a pro-regenerative ECM characterized by early hyaluronic acid (HA) deposition and increased levels of pro-regenerative collagens such as type III collagen. Since HA is also a regulator of collagen organization, we propose that early accumulation of HA by fibroblasts can facilitate a pro-regenerative matrix formation. Given that the molecular weights of HA present in pro-regenerative matrix are higher than synthetic HA, we strategize attracting HA synthesized by fibroblasts. In this study, we used a synthetic peptide sequence known to have affinity to HA as a strategy to instruct fibroblasts to retain HA on the surface. We hypothesized that hyaluronic acid binding peptide (HABP) may instruct fibroblast endogenous HA deposition onto functionalized surfaces. We functionalized silica glass surfaces with HABP using aminoorganosilane mediated chemisorption and screened primary human dermal fibroblasts (hDF) for cell morphology, cytoskeletal arrangement, and alpha-smooth muscle actin (α-SMA) expression. Our results show HABP treated surfaces retain higher levels of HA on silica glass compared to control surfaces on fibroblast derived matrices. Analysis of α-SMA shows increased α-SMA expression on hDFs and increased stress fiber formation. HABP treated surfaces were found to have reduced α-SMA expression. The physical features of collagen fibers deposited by fibroblasts were also organized differently in the presence of HABP. We propose that HABPs are a potentially viable strategy to instruct pro-regenerative fibroblasts and can be used therapeutically to treat fibrotic diseases.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-22"},"PeriodicalIF":2.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rat Hemolymph Nodes Provide a Direct Communication Site for Macrophages Interacting with Erythrocytes and Mast Cells.","authors":"Manabu Yamada, Emi Aizawa, Akihiro Dohi, Kenichi Sasaguri, Toshiharu Yamamoto, Tadahide Noguchi","doi":"10.1159/000543747","DOIUrl":"10.1159/000543747","url":null,"abstract":"<p><strong>Introduction: </strong>Hemolymph nodes, characterized by erythrocyte rosettes, are found in humans and animals, including rats. The cytoarchitectural features that these nodes exhibit compared with those of ordinary lymph nodes and spleen are unknown. Herein, we describe the cytoarchitecture of rat hemolymph nodes.</p><p><strong>Methods: </strong>We performed immunohistochemical analyses with antibodies against CD68, Iba-1, CD3, CD20, and S-100. Hematoxylin and eosin staining was used to compare findings with sections from ordinary lymph nodes and spleen.</p><p><strong>Results: </strong>Hemolymph nodes exhibited erythrocyte rosettes with macrophages immunopositive for CD68, Iba-1, and CD3, which were rare in the physiologically normal spleen and lymph nodes. Additionally, sinusoidal macrophages often showed close apposition to erythrocytes and mast cells. Accumulation of cells immunoreactive to CD20, a B-lymphocyte marker, was seen only in the germinal centers of ordinary lymph nodes, not in the hemolymph nodes or spleen. Ordinary lymph nodes and spleen showed well-developed reticular configurations of cells with immunoreactivity for S-100, a marker for dendritic cells, unlike hemolymph nodes, suggesting less-developed antigen-presenting ability in the latter. Despite similarities to ordinary lymph nodes and spleen, the direct contact with erythrocytes and mast cells in the hemolymph nodes suggests a facilitation of direct cell-to-cell communication for macrophages, erythrocytes, and mast cells.</p><p><strong>Conclusion: </strong>Our findings imply that the hemolymph nodes are a unique immune organ, differing from ordinary lymph nodes and spleen.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-10"},"PeriodicalIF":2.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hedgehog Signaling during Gut Formation in the Freshwater Leech, Helobdella austinensis.","authors":"Brenda I Medina-Jiménez, Hee-Jin Kwak, Yam Prasad Aryal, Chan-Jun Lee, Geon-Hwi Jeong, In-Hyeok Pyo, Hyeonwoo Park, Sangjune Kim, Soon Cheol Park, Sung-Jin Cho","doi":"10.1159/000543782","DOIUrl":"10.1159/000543782","url":null,"abstract":"<p><strong>Introduction: </strong>The hedgehog signaling pathway plays a crucial role in inducing segment polarity through cell-cell interactions in various metazoans, including arthropods and annelids. However, its involvement in organogenesis and segmentation among lophotrochozoans remains inconsistent. This study aimed to explore the role of the hedgehog gene during gut development in the freshwater leech, Helobdella austinensis.</p><p><strong>Methods: </strong>Developmental RT-PCR and in situ hybridization were performed to examine the expressions of hedgehog genes. In addition, embryos were treated with cyclopamine (a hedgehog signaling antagonist) and purmorphamine (a Smo agonist) to examine the potential interactions between Helobdella orthologs to hedgehog and two NKL genes: Hau-NK2 and Hau-NK4.</p><p><strong>Results: </strong>We examined the expressions of four core pathway members - Hedgehog (Hh), Patched (Ptc), Smoothened (Smo), and the downstream transcription factor Gli - spatiotemporally during the embryonic stages of H. austinensis. All four genes were expressed in the developing gut and proboscis during organogenesis but not during the segmentation stage. Additionally, the treatment of embryos with cyclopamine and purmorphamine revealed that NK genes are regulated by hedgehog signaling. Furthermore, NK2 and NK4 were expressed in the developing gut rather than in a segmental stripe pattern.</p><p><strong>Conclusion: </strong>This study confirms that the hedgehog signaling pathway is associated with gut development in the freshwater leech, H. austinensis. The expression patterns of hedgehog pathway genes and their interaction with NK genes suggest a role of hedgehog signaling in regulating gut development rather than segmentation in the freshwater leeches.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-12"},"PeriodicalIF":2.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carbonic Anhydrase IV Deficiency Causes Intrauterine Embryonic Loss in Mice.","authors":"Sven Schumann, Susanne Camilla Grund, Jaroslaw Thomas Dankert, Ruth Grümmer, Gunther Wennemuth","doi":"10.1159/000544000","DOIUrl":"10.1159/000544000","url":null,"abstract":"<p><strong>Introduction: </strong>Members of the carbonic anhydrase gene family, responsible for the reversible hydration of carbon dioxide, participate in several important biological processes including processes involved in fertilization. CAIV has been shown to play a role in sperm cell capacitation and regulation of sperm motility and is present in mature murine placentae. The present study specifically analyzes the distribution of CAIV in female reproductive organs and during early placenta development.</p><p><strong>Methods: </strong>Immunostaining for CAIV was performed on female reproductive organs (ovary, fallopian tube, uterus, vagina) of nonpregnant mice and on implantation sites of early pregnancy between 4.5 and 9.5 days post-coitum (dpc). Sex typing of embryos was performed by PCR using three separated gene combinations for X and Y chromosomes, respectively. Additionally, reproductive outcome of CAIV-deficient mice was determined.</p><p><strong>Results: </strong>CAIV is largely absent in the female reproductive organs of nonpregnant mice. Immunostaining for CAIV was present in the blastocyst and in consecutive stages of the developing embryo. In the endometrial epithelium distant from the implantation chamber, CAIV is induced from 8.5 dpc onward. Moreover, the yolk sac epithelium, the trophoblast giant cells, and the labyrinthine compartment of the developing hemochorial placenta show a strong immunostaining for CAIV. In heterozygous mating, the number of CAIV knockout pups is significantly reduced than was to be expected according to the mendelian rules, while homozygous mating of CAIV knockout mice results in a significant reduction of litter size, which is mainly due to a reduced number of female mice born. Since at 9.5 dpc the number of female embryos is rather higher than that of males, the observed reduction of female offspring appears to be due to a defect in placentation after 9.5 dpc.</p><p><strong>Conclusion: </strong>Thus, CAIV seems to be involved in the signaling network of embryo development, implantation, and placentation.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-11"},"PeriodicalIF":2.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}