Theriogenology最新文献

{"title":"L-proline supplementation in the freezing medium enhances the viability and quality of bovine blastocysts after slow freezing and thawing","authors":"Seungki Jung ,&nbsp;Yeonsub Jung ,&nbsp;Hyeonseok Sul ,&nbsp;Yeon-Gil Jung ,&nbsp;Jaehyung Ham ,&nbsp;Dongjin Oh ,&nbsp;Joohyeong Lee ,&nbsp;Sang-Hwan Hyun","doi":"10.1016/j.theriogenology.2025.117399","DOIUrl":"10.1016/j.theriogenology.2025.117399","url":null,"abstract":"<div><div>L-proline (Pro) is a natural amino acid with known antioxidant and cryoprotectant activity. This study aimed to assess the impact of Pro supplementation in freezing medium on blastocyst survival and quality. <em>In vitro</em> fertilization (IVF) was conducted using oocytes collected from Korean cattle, and Day 7 blastocysts were cryopreserved through slow freezing. Optimal post-thaw blastocyst survival was determined by adding various Pro concentrations to the freezing medium. Additionally, the effect of Sucrose (Suc) alone or in conjunction with Pro was evaluated. To assess blastocyst quality, we analyzed reactive oxygen species (ROS) levels, apoptosis, and gene expression in blastocysts that survived 24 h after slow freezing-thawing. The hatching rate at 72 h was significantly higher in the 0.3 M Pro group than that in the 0 M group (p = 0.0466). The hatching rates at 48 and 72 h were significantly higher in the Pro group than in the Suc and Suc + Pro groups (48 h: Suc, p = 0.0037; Suc + Pro, p = 0.0052; 72 h: Suc, p = 0.0024; Suc + Pro, p = 0.0009). ROS levels and the apoptosis index were significantly lower in the Pro group than in the Suc group (p = 0.0099, and 0.0098, respectively). Furthermore, mRNA expression of <em>HSPA1A</em> was significantly lower in the Pro and Suc + Pro groups than in the Suc group (p = 0.0074, and p = 0.01174, respectively). Additionally, <em>GCLC</em> mRNA expression was significantly higher in the Pro group than in the Suc group (p = 0.0308). These findings indicate that Pro supplementation in a slow freezing medium enhances the viability and quality of embryos.</div></div>","PeriodicalId":23131,"journal":{"name":"Theriogenology","volume":"240 ","pages":"Article 117399"},"PeriodicalIF":2.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143714609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DDX5 regulates asymmetric division of mouse oocytes by modulating the stability of microfilament-associated protein radixin","authors":"Lina Yu ,&nbsp;Ruixin Shi ,&nbsp;Yan Mao ,&nbsp;Aolei Guo ,&nbsp;Lihua Zhu ,&nbsp;Guangyi Cao","doi":"10.1016/j.theriogenology.2025.117401","DOIUrl":"10.1016/j.theriogenology.2025.117401","url":null,"abstract":"<div><div>Mammalian oocytes arrest at prophase I and resume meiosis upon germinal vesicle breakdown, leading to asymmetric division and formation of a smaller polar body and larger oocyte, crucial for genome segregation and cytoplasmic distribution. Actin filaments regulate this division, with reorganization involving actin cap formation and cytoplasmic network changes, mediated by actin-binding proteins like myosins and radixin. DDX5, an RNA helicase, is implicated in transcription, RNA metabolism, and early embryonic development, though its regulatory mechanisms in oocyte maturation remain unclear. Here, we demonstrate that DDX5 regulates cytokinesis during mouse oocyte meiotic maturation. DDX5 colocalizes with the spindle upon meiotic resumption, and its inhibition impairs polar body extrusion and cytokinesis. RNA-seq reveals disrupted mRNA homeostasis upon DDX5 depletion, while IP-MS identifies its interaction with actin cytoskeletal proteins, including radixin, whose expression is significantly reduced. Our findings reveal that DDX5 modulates oocyte cytokinesis by regulating actin cytoskeleton dynamics, underscoring its critical role in asymmetric division.</div></div>","PeriodicalId":23131,"journal":{"name":"Theriogenology","volume":"240 ","pages":"Article 117401"},"PeriodicalIF":2.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estrus, preovulatory LH surge and oocyte maturation in Goettingen miniature pigs (Sus scrofa domesticus)","authors":"Wagdy K.B. Khalil ,&nbsp;Christine Wrenzycki ,&nbsp;Wolfgang Holtz","doi":"10.1016/j.theriogenology.2025.117397","DOIUrl":"10.1016/j.theriogenology.2025.117397","url":null,"abstract":"<div><div>Many studies dealing with ovarian activity and oocyte maturation in pigs were conducted on gilts and sows in which ovarian activity had been induced with synchronizing hormones. The present study was conducted to characterize the naturally occurring processes. Duration of the estrus cycle and estrous behavior, monitored over 229 estrus cycles of 50 gilts (4.6 cycles/gilt) were 21.3 (SEM 0.08) d and 2.90 (SEM 0.06) d, respectively. Periestrous serum concentrations of progesterone and LH were determined in 50 gilts provided with permanently indwelling jugular catheters. The LH surge commenced 1.6 (SEM 1.6) h before the onset of the immobility reflex and climaxed 8.6 (SEM 1.5) h later. The duration of the LH surge was 27.9 (SEM 1.3) h; its amplitude was 2.8 (SEM 0.3) ng/mL. There was considerable individual variation in timing and pattern of LH release. Before and 6, 12, 18, 24, 30 and 36 h after the onset of the immobility reflex 7 to 10 gilts were sacrificed. Ovarian structures were recorded and cumulus oocyte complexes (COCs) from small follicles (&lt;4 mm), large follicles (≥4 mm), ovarian bursa and oviduct were subjected to cytogenetic (meiotic progression) and molecular (mRNA concentration) studies. Oocytes from follicles &lt;4 mm in diameter did not respond to the preovulatory LH surge, whereas oocytes in follicles ≥4 mm in diameter resumed meiotic progress to metaphase II. The relative abundance of CDC2, Cyclin B, ERK2 and c-mos gene transcripts was assessed by semi-quantitative RT-PCR in oocytes from follicles (&lt;4 mm and ≥4 mm in diameter) as well as in post ovulatory oocytes. The amount of mRNA for each of the four genes investigated was higher in oocytes from follicles &lt;4 mm than in those from follicles ≥4 mm in diameter. Differences were significant after 20 h for CDC2 and ERK2 transcripts. mRNA content for each of the four genes was significantly lower in ovulated than in non-matured (follicular) oocytes. It is concluded that in follicles ≥4 mm in diameter the LH surge induces oocyte maturation, a process where stored mRNA is used to synthesize the proteins relevant for continued oocyte maturation, viz. maturation promoting factor (MPF), mitogen activated protein (MAP) and c-mos.</div></div>","PeriodicalId":23131,"journal":{"name":"Theriogenology","volume":"240 ","pages":"Article 117397"},"PeriodicalIF":2.4,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EIF4E1B interacts with HSPA1A and PPP2CA and is involved in mouse oocyte maturation and early embryonic development","authors":"Zengyou Ma ,&nbsp;Yanyan Zhang ,&nbsp;Xueqi Tian ,&nbsp;Wenjie Lu ,&nbsp;Hui Peng","doi":"10.1016/j.theriogenology.2025.117398","DOIUrl":"10.1016/j.theriogenology.2025.117398","url":null,"abstract":"<div><div>The protein translation process is an important part of mammalian ovogenesis and early embryonic development. The eukaryotic translation initiation factors 4E family (eIF4E) initiates the eukaryotic mRNA translation process and plays an important role in protein synthesis. The aim of this research was to analyze the expression and localization of eIF4E family members and the role of EIF4E1B in mouse oocyte maturation and early embryonic development. Here, we report the expression and localization of EIF4E1, EIF4E2, and EIF4E3 in multiple tissues, during oocyte maturation and early embryonic development in mice. However, EIF4E1B was expressed only in ovarian and testicular tissues, and this protein was detected only at the one-to two-cell embryonic stage of early embryos. Moreover, knockdown of <em>eIF4E1b</em> in GV-stage oocytes and zygotes resulted in significant reductions in the rates of oocyte maturation and blastocyst formation, respectively. Further investigation revealed that EIF4E1B interacted with the PPP2CA and HSPA1A proteins and might be involved in the mouse oocyte maturation process. These results provide the first evidence for a novel function of EIF4E1B in oocyte maturation and early embryonic development in mice.</div></div>","PeriodicalId":23131,"journal":{"name":"Theriogenology","volume":"240 ","pages":"Article 117398"},"PeriodicalIF":2.4,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interference with the interaction between sperm arylsulfatase A and sulfated carbohydrate chain residues of the zona pellucida effectively suppresses polyspermy during in vitro fertilization of porcine oocytes","authors":"Saki Sakamura ,&nbsp;Kokoro Kawasaki ,&nbsp;Kenichi Yamanaka ,&nbsp;Hideki Tatemoto","doi":"10.1016/j.theriogenology.2025.117396","DOIUrl":"10.1016/j.theriogenology.2025.117396","url":null,"abstract":"<div><div>The present study investigated the effects of treatments with sulfatase to desulfate the sulfated carbohydrate chain residues of the zona pellucida (ZP) and arylsulfatase A-blocking peptide (ARSA-BP) for the specific masking of sperm ARSA on the interaction of sperm ARSA with ZP, which plays an important role in the <em>in vitro</em> fertilization (IVF) of porcine oocytes. The pretreatment of oocytes with sulfatase for 10 min before the onset of insemination or the addition of 5 ng/mL ARSA-BP to IVF medium significantly reduced the incidence of polyspermy; however, these treatments did not affect sperm penetrability or male pronucleus formation. Combined treatments with sulfatase plus ARSA-BP significantly reduced the incidence of polyspermy to the range of 23–26 % under conditions maintaining a high sperm penetration rate from that of untreated oocytes (56 %). Although the treatments with sulfatase or ARSA-BP alone and sulfatase plus ARSA-BP during IVF did not affect the number of sperm that bound to the ZP or ZP solubility, the incidence of sperm with the acrosome reaction that bound to the ZP was efficiently reduced by the treatment. In oocytes treated with ARSA-BP but not sulfatase, developmental potency to the blastocyst stage was enhanced by decreasing the number of apoptotic blastomeres. Therefore, the present results clearly indicate that interference with the interaction between sperm ARSA and sulfated ZP glycoprotein residues reduced the induction of the acrosome reaction in sperm that bound to the ZP, effectively suppressing polyspermy during porcine IVF.</div></div>","PeriodicalId":23131,"journal":{"name":"Theriogenology","volume":"240 ","pages":"Article 117396"},"PeriodicalIF":2.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sperm metabolomics identifies freezability markers in Duroc, Landrace, and Large White boars","authors":"Meicheng Li ,&nbsp;Yifan Bai ,&nbsp;Jiajun Zhang ,&nbsp;Hongyang Wang ,&nbsp;Junjie Li ,&nbsp;Wenjun Wang","doi":"10.1016/j.theriogenology.2025.117395","DOIUrl":"10.1016/j.theriogenology.2025.117395","url":null,"abstract":"<div><div>Cryopreservation of boar semen is widely applied in the conservation of genetic resources and animal breeding to enhance the utilization efficiency of superior boars. However, accurately identifying individuals with good freezing tolerance in boar sperm remains challenging. In this study, based on the differences in sperm motility before and after cryopreservation from 328 boars, we selected six boars each from the Duroc, Landrace, and Large White breeds, and categorized them into poor freezability ejaculates (PFE) and good freezability ejaculates (GFE) groups for sperm metabolomic analysis. A total of 1288 metabolites were identified using both positive and negative ion modes. There were 148 differentially expressed metabolites between the GFE and PFE groups, which were enriched in pathways such as alanine, aspartate and glutamate metabolism; arginine biosynthesis; D-amino acid metabolism; histidine metabolism; beta-alanine metabolism; citrate cycle (TCA cycle); pantothenate and CoA biosynthesis; and pyruvate metabolism. Further analysis, including ROC curve evaluation, identified seven potential biomarkers for sperm cryopreservation. Argininosuccinic acid, asparagine, L-aspartate, fumarate, D-ornithine, DL-serine and histidine were tightly interconnected in a series of amino acids metabolism. In conclusion, our findings imply that differences in certain amino acid biosynthetic pathways contribute to the variations in freezing tolerance of boar sperm.</div></div>","PeriodicalId":23131,"journal":{"name":"Theriogenology","volume":"240 ","pages":"Article 117395"},"PeriodicalIF":2.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143654534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of genotype-environment interaction on stress parameters during spontaneous farrowing in modern and traditional pig breeds housed in crates and pens","authors":"M. Oster ,&nbsp;C.A. Gladbach ,&nbsp;A. Vernunft ,&nbsp;H. Reyer ,&nbsp;W. Otten ,&nbsp;C.C. Metges ,&nbsp;E. Muráni ,&nbsp;S. Ponsuksili ,&nbsp;K. Frölich ,&nbsp;K. Wimmers ,&nbsp;H. Bostedt","doi":"10.1016/j.theriogenology.2025.117394","DOIUrl":"10.1016/j.theriogenology.2025.117394","url":null,"abstract":"<div><div>The transition from farrowing crates to farrowing pens aims to improve animal welfare by enabling the expression of maternal behavioural profiles. This study examines the spontaneous farrowing process in both farrowing crates and pens for modern German Landrace (GL) and traditional German Saddleback (GS) pigs — two breeds with different breeding histories and adaptations to housing systems. The goal is to investigate whether, and how, both breeds benefit equally from farrowing pens. From the birth of the first piglet until 1 h after the last delivery (<em>intrapartum</em>; <em>ip</em>), half-hourly blood samples were collected from catheterized sows in addition to blood samples retrieved from <em>antepartum</em> (<em>ap</em>) and <em>postpartum</em> (<em>pp</em>) periods. After spontaneous, non-induced farrowing, the traditional GS breed exhibited a significantly shorter gestation length, smaller litter weight, and a lower incidence of labour dystocia compared to modern GL sows. Breed effects were observed for profiles of heart rate (<em>ip</em>: GL &gt; GS), cortisol (<em>ap</em>: GL &lt; GS; <em>ip</em>: GL &lt; GS), adrenaline (<em>ap</em>: GL &lt; GS), noradrenaline (<em>ip</em>: GL &lt; GS), non-esterified fatty acids (<em>ap</em>: GL &lt; GS; <em>ip</em>: GL &lt; GS), glucose (<em>ap</em>: GL &gt; GS), and β-hydroxybutyrate (<em>ap</em>: GL &lt; GS) at distinct <em>peripartum</em> periods. Effects due to housing appeared for heart rate (<em>ap</em>: crate &gt; pen) as well as respiratory rate (crate &lt; pen) and adrenaline (crate &gt; pen) at distinct time points. Taken together, breed-specific endocrine control and energy-related metabolic properties might suggest a need for tailored housing conditions during parturition for modern and traditional sows.</div></div>","PeriodicalId":23131,"journal":{"name":"Theriogenology","volume":"240 ","pages":"Article 117394"},"PeriodicalIF":2.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multidimensional data analysis algorithms facilitate and speed the analysis, and provide improved visualization of flow cytometry data in spermatology","authors":"Laura Becerro-Rey,&nbsp;Francisco Eduardo Martín-Cano,&nbsp;María Cruz Gil,&nbsp;Cristina Ortega-Ferrusola,&nbsp;Eloy Redondo,&nbsp;Javier Masot,&nbsp;Eva da Silva-Álvarez,&nbsp;Fernando J. Peña","doi":"10.1016/j.theriogenology.2025.117393","DOIUrl":"10.1016/j.theriogenology.2025.117393","url":null,"abstract":"<div><div>Modern flow cytometers enable the simultaneous analysis of an increasing number of parameters or dimensions, offering significant advantages for andrological assessments. However, relying on conventional procedures for data processing increases the complexity of the analysis and the time required to complete it. We propose a simplified and efficient protocol that leverages commercial software and dimensional reduction algorithms for multiparametric flow cytometry data analysis, to improve data visualization and speed up the analysis. Ejaculates from six stallions were split into two media, a modified Tyrode's containing 67 mM glucose and 10 mM pyruvate or a commercial media containing 67 mM glucose but not pyruvate and stored at room temperature for 48 h. A five-color panel was designed to assess key sperm parameters, including viability, membrane permeability, mitochondrial membrane potential, mitochondrial mass, and apoptotic changes. Data were uploaded to FlowJo 10.10 for Mac, where automatic compensation and conventional 2D plot analyses were performed on the compensated files. In a second analysis, individual files were concatenated (merged) in FlowJo, generating new.fcs files, which were subsequently downsampled from 50,000 to 3000 events (spermatozoa) per file. The downsampled, concatenated files were exported and analyzed in Cytobank (<span><span>https://premium.cytobank.org</span><svg><path></path></svg></span>). Preprocessing included Arcsinh transformation for improved population visualization, automated compensation, and the exclusion of non-sperm debris, clumps, and doublets. Initial 2D plots were generated for each condition, providing a baseline comparison. Dimensionality reduction and clustering analyses were then performed on the same merged files. Our results showed that the proportions of sperm subpopulations identified by advanced analytical approaches, such as downsampling, dimensional reduction, and clustering, were consistent with those obtained via traditional 2D dot-plot analysis. This study demonstrates the feasibility and accuracy of advanced methodologies for flow cytometric analysis of spermatozoa. These approaches enhance processing speed, improve data visualization, and offer deeper insights into the dynamics of sperm subpopulations under varying metabolic conditions.</div></div>","PeriodicalId":23131,"journal":{"name":"Theriogenology","volume":"239 ","pages":"Article 117393"},"PeriodicalIF":2.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inverse embryonic responses of In vivo and In vitro fertilized mouse embryos to vitamin B supplementation during preimplantation period with limited long-term risks","authors":"Norermi Firzana Alfian ,&nbsp;Masashi Hisamoto ,&nbsp;Satoshi Kishigami","doi":"10.1016/j.theriogenology.2025.117392","DOIUrl":"10.1016/j.theriogenology.2025.117392","url":null,"abstract":"<div><div>Vitamin supplementation is commonly used for peri-conceptual consumption, but the long-term impacts are not yet understood. We examined the effects of adding vitamins riboflavin (B2) and pyridoxine (B6) to culture medium on embryo quality produced from <em>in vitro</em> fertilization (IVF) and <em>in vivo</em> fertilization (IVV). At the two-cell stage, IVF and IVV embryos were cultured in a standard medium, Chatot-Ziomel-Bavister (CZB) with (IVV_B2B6 and IVF_B2B6) or without adding vitamins B2 and B6 (IVV_CZB and IVF_CZB). For IVV_B2B6, vitamin supplementation presented lowered total cell numbers by an elevated inner cell mass (ICM) and reduced trophectoderm (TE) cells (Total cell numbers: IVV_CZB = 57 ± 1.6, IVV_B2B6 = 44 ± 1.9, IVF_CZB = 45 ± 1.6, and IVF_B2B6 = 60 ± 4.0; P &lt; 0.0001). In contrast, the IVF_B2B6 group showed an inverse response by increased TE cells and reduced placental efficiency after embryo transfer, (fetal:placental ratio: natural mating = 22.7 ± 1.0, IVV_CZB = 11.2 ± 0.7, IVV_B2B6 = 12.8 ± 1.2, IVF_CZB = 12.7 ± 0.5, and IVF_B2B6 = 9.5 ± 0.4; P &lt; 0.0002). To investigate the relationship of vitamin B2 and B6 with one-carbon metabolism, by immunostaining heterochromatin methylation levels with H3K27me3. This showed significantly increased intensities in the IVV_B2B6 group but not in the IVF_B2B6. Oral glucose tolerance test indicated an increased area under the curve (iAUC) in IVV_B2B6 at the early adult stage. Our findings suggest that embryo development trajectory with vitamin supplementation is influenced by the method of fertilization, leading to diverse responses.</div></div>","PeriodicalId":23131,"journal":{"name":"Theriogenology","volume":"239 ","pages":"Article 117392"},"PeriodicalIF":2.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual roles of the TLR2/TLR4/NLRP3-H-PGDS-PGD2 axis in regulating the inflammatory response in Escherichia coli-infected bovine bone marrow-derived macrophages and endometrial tissue","authors":"Xiaolin Yang ,&nbsp;Shuangyi Zhang ,&nbsp;Bo Liu ,&nbsp;Wei Mao ,&nbsp;Pengfei Gong ,&nbsp;Lili Guo ,&nbsp;Jingze Wu ,&nbsp;Yi Zhao ,&nbsp;Yongfei Wang ,&nbsp;Surong Hasi ,&nbsp;Jinshan Cao","doi":"10.1016/j.theriogenology.2025.117374","DOIUrl":"10.1016/j.theriogenology.2025.117374","url":null,"abstract":"<div><div>Endometritis in dairy cows is associated with pathogenic microorganisms, local inflammatory injuries, and uterine microecological disorders. <em>Escherichia coli</em> (<em>E. coli</em>) is the primary pathogen responsible for bovine endometritis onset; however, the underlying pathomechanisms remain unclear. In this study, we aimed to investigate <em>E. coli</em>-induced endometritis mechanisms in dairy cows using bovine bone marrow-derived macrophages and endometrial tissue. Following <em>E. coli</em> infection of macrophages, we observed a significant increase in the mRNA expression levels of innate immune recognition receptors, including toll-like receptor 2 (<em>TLR2</em>), toll-like receptor 4 (<em>TLR4</em>), and nucleotide-binding oligomerization domain-like receptor protein 3 (<em>NLRP3</em>), as well as prostaglandin D₂ (PGD₂)-related enzymes (<em>cyclooxygenase-2</em> and <em>hematopoietic prostaglandin D synthase</em>). Furthermore, the secretion of PGD₂, a major mediator of inflammation, was markedly upregulated. In <em>E. coli</em>-infected macrophages, TLR2, TLR4, and NLRP3 increased the secretion of inflammatory mediators, including PGD₂, by activating mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB). This lead to enhanced inflammatory response. During early <em>E. coli</em> infection, PGD₂ inhibitors reduced the secretion of inflammatory mediators by modulating MAPK and NF-κB pathway activation and enhancing macrophage bacterial killing, thereby alleviating endometrial tissue damage in dairy cows. In contrast, in the later stages of infection, PGD₂ inhibitors exacerbated the inflammatory response and impaired the killing capacity of macrophages, which lead to increased endometrial tissue damage. Therefore, our findings highlight that TLR2, TLR4, and NLRP3 are pivotal in regulating PGD₂ secretion during <em>E. coli</em>-induced endometritis in dairy cows. PGD₂ had a pro-inflammatory effect in the early stages of <em>E. coli</em> infection and anti-inflammatory effects in the later stages. These findings can help develop strategies benefiting endometritis treatment.</div></div>","PeriodicalId":23131,"journal":{"name":"Theriogenology","volume":"239 ","pages":"Article 117374"},"PeriodicalIF":2.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143644240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}