Reproduction最新文献

{"title":"CD40 ligand and CD40: expression, regulation and function at the maternal-conceptus interface in pigs.","authors":"Inkyu Yoo, Soohyung Lee, Yugyeong Cheon, Tae Sub Park, Hakhyun Ka","doi":"10.1530/REP-24-0396","DOIUrl":"10.1530/REP-24-0396","url":null,"abstract":"<p><strong>In brief: </strong>The CD40 ligand-CD40 signaling system expressed at the maternal-conceptus interface in pigs is involved in regulating maternal immunity by modifying endometrial endothelial cell function during early pregnancy. This paper reveals the role of CD40 ligand-CD40 signaling at the maternal-conceptus interface in pigs.</p><p><strong>Abstract: </strong>To successfully establish and maintain pregnancy in pigs, a variety of factors must work together at the maternal-conceptus interface to form an immune environment appropriate for both the mother and the conceptus. Our transcriptomics study has shown that cluster of differentiation ligand 40 (CD40L) and its receptor CD40, which are known to play important roles in regulating cell- and antibody-mediated immunity, are expressed in the endometrium during early pregnancy. However, the roles of the CD40L and CD40 signaling system are not well understood. Therefore, we determined the expression, regulation and function of CD40L and CD40 at the maternal-conceptus interface in pigs. The endometrium expressed CD40L and CD40 mRNAs at the greatest levels on day 15 of pregnancy. The CD40L protein was localized predominantly to luminal epithelial cells on day 15 of pregnancy, and the CD40 protein was found in luminal epithelial, stromal and vascular endothelial cells in the endometrium during pregnancy. During early pregnancy, the conceptus expressed CD40 but not CD40L and chorioallantoic tissues during mid- to late pregnancy expressed both CD40L and CD40. Interferon-γ increased the expression of CD40L and CD40 in endometrial explants. CD40L increased the migration but not the proliferation of cultured porcine uterine endothelial (pENDO) cells in vitro. In addition, CD40L affected the expression of genes related to angiogenesis, cell adhesion, chemokines and immunity in pENDO cells. These results suggest that the CD40L-CD40 system might play an important role in the establishment of pregnancy in pigs by regulating endometrial endothelial cell function during the implantation period.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diminazene aceturate, an ACE2 activator, ameliorates testicular injury in diet-induced obese mice.","authors":"Xiaofeng Yue, Rui Yin, Liling Wu, Jinjin Li, Jianwu Wang, Benhuang Yan, Lingyong Dai, Chongxing Shen, Yi Zhi, Ling Wan, Jigao Yang, Weibing Li","doi":"10.1530/REP-24-0242","DOIUrl":"10.1530/REP-24-0242","url":null,"abstract":"<p><strong>In brief: </strong>Obesity is a prevalent health concern globally, often associated with testicular damage that can lead to male infertility. This study investigates the improvement of obesity-induced testicular damage by ACE2 agonist diminazene aceturate (DIZE) and explores the role of the ACE2/Ang 1-7/MasR axis in this process.</p><p><strong>Abstract: </strong>DIZE improved obesity and metabolic disturbances in diet-induced obesity (DIO) mice. An increase in sperm count and motility, along with improved morphology and increased male fertility, was observed after DIZE treatment. Both serum and intratesticular testosterone levels showed an increase. Moreover, ACE2/Ang 1-7/MasR protein levels in the testes were restored, which inhibited germ cells apoptosis, lipid accumulation and oxidative stress, and elevated testosterone synthesis-related proteins. However, the MasR antagonist A779 partially counteracted the improving effects of DIZE on metabolism and the testes of DIO mice. This study shows that DIZE treatment has protective effects against obesity-induced testicular injury by activating the ACE2/Ang 1-7/MasR axis.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recombinant FSH induced progesterone via partially regulating let-7 expression in human and mouse granulosa cells.","authors":"Jing Chen, Lin Chen, Weimin Liu","doi":"10.1530/REP-24-0074","DOIUrl":"10.1530/REP-24-0074","url":null,"abstract":"<p><strong>In brief: </strong>The administration of recombinant follicle-stimulating hormone (rFSH) during in vitro fertilization (IVF) cycles in clinics may lead to premature progesterone rise, adversely affecting the success rates of assisted reproductive techniques. This study uncovers a potential mechanism through which rFSH stimulates progesterone production in human and mouse samples.</p><p><strong>Abstract: </strong>Serum progesterone may increase prior to ovulation trigger in in vitro fertilization (IVF) patients, jeopardizing endometrial receptivity and therefore live birth rate. rFSH promotes progesterone production from human granulosa cells. Yet, the role of FSH in progesterone production needs deeper exploration. Studies were conducted in human primary cumulus cells from IVF cycles, a human granulosa cell line and mouse primary granulosa cells. The relative expression of Lethal-7 (let-7) was evaluated using real-time reverse transcription polymerase chain reaction (real-time RT-PCR). Human primary cumulus cells were collected from individual cumulus-oocyte complexes of high-progesterone patients (serum progesterone level higher than 5 nM, n = 18) and a control group (serum progesterone level less than 5 nM, n = 25). The expression of let-7a in human primary cumulus cells was markedly reduced in the high-progesterone group compared to the control. The serum progesterone level was augmented after rFSH treatment at doses of 0.5, 1 and 2.5 IU along with reduced expression of let-7a. Progesterone levels in the cultured medium from isolated mouse primary granulosa cells and the human granulosa cell line were significantly elevated with rFSH at 12.5, 25 and 50 IU/L concentrations, with decreased expression of let-7a. In addition, there was a robust increase in let-7a expression in the let-7a mimics-transfected group and a decrease in the let-7a inhibitor group with or without rFSH treatment, showing the opposite trend of progesterone. Collectively, our findings revealed the key role of let-7 in rFSH-induced progesterone levels in both human and mouse granulosa cells, providing a potential mechanism for premature progesterone rise.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TEAD3 and TEAD4 play overlapping role in bovine preimplantation development.","authors":"Haotian Yu, Yan Shi, Xiaotong Wu, Bingjie Hu, Hao Jin, Yassin Kassim, Tariq Iqbal, Omaima Mohamed Kandil, Esraa Aly Ismail, Huanan Wang, Shaohua Wang, Kun Zhang","doi":"10.1530/REP-24-0307","DOIUrl":"10.1530/REP-24-0307","url":null,"abstract":"<p><strong>In brief: </strong>Transcription factors are crucial for lineage specification in the preimplantation development of mammals. This research shows that TEAD3 and TEAD4 play important and overlapping functions in directing trophectoderm fate decisions during this developmental stage in cattle.</p><p><strong>Abstract: </strong>During mammalian preimplantation development, the transition from morula to blastocyst is a critical biological event. This process involves polarization and initial specification of lineages, regulated by various transcription factors that have been extensively studied in mice. Our single-cell RNA sequencing analyses revealed that TEAD3 is specifically expressed in the trophectoderm cells of bovine preimplantation embryos, unlike in mice. The objective of this study is to determine the functional role of TEAD3 in bovine preimplantation development. While TEAD3 knockdown does not affect blastocyst formation in cattle, embryos fail to progress to the blastocyst stage when both TEAD3 and TEAD4, another member of the TEAD family, are disrupted using RNA interference and base editing techniques, respectively. This finding suggests a redundant role for TEAD3 and TEAD4 during preimplantation development in cattle. RNA sequencing analysis identified dysregulation of 215 genes, with 53 genes upregulated and 162 genes downregulated. Notably, we observed a reduction in the expression of trophectoderm lineage-specific genes KRT8, KRT18 and EZR and HIPPO signaling pathway components. Immunofluorescence analysis further revealed that the protein expression levels of KRT8 and EZR were significantly decreased. Importantly, the initial expression of trophectoderm lineage-specific genes, such as TFAP2C and GATA3, and the inner cell mass lineage-specific genes, such as OCT4, remained unaffected. This contrasts with the role of TEAD4 in directly regulating the trophectoderm lineage specification in mice. Thus, our studies demonstrate that TEAD3 and TEAD4 play essential and redundant roles upstream of trophectoderm fate decisions during preimplantation development in cattle.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Key glycometabolism during oocyte maturation and early embryonic development.","authors":"Yichuan Zhang, Tianjie Li, Yibo Wang, Yang Yu","doi":"10.1530/REP-24-0275","DOIUrl":"10.1530/REP-24-0275","url":null,"abstract":"<p><strong>In brief: </strong>Glucose metabolism is central to the successful progression from oocyte maturation to blastocyst formation, influencing not only energy production but also key developmental decisions and epigenetic regulation. This review uncovers the intricate interplay between glucose, fatty acids, amino acids and nucleotides, highlighting their crucial roles in early embryonic development and exploring how noninvasive metabolic monitoring can revolutionize embryo selection and personalized assisted reproductive technologies, offering new hope for fertility treatments.</p><p><strong>Abstract: </strong>In recent decades, it has become increasingly clear that mammalian gametes and early embryos are highly sensitive to metabolic substrates. With advances in single-cell sequencing, metabolomics and bioinformatics, we now recognize that metabolic pathways not only meet cellular energy demands but also play a critical role in cell proliferation, differentiation and fate determination. Investigating metabolic processes during oocyte maturation and early embryonic development is thus essential to advancing reproductive medicine and embryology. This review highlights the intricate metabolic pathways, particularly glucose metabolism, that drive the transition from an oocyte to an embryo. These processes involve a complex interaction of signaling pathways, nutrient availability and environmental factors, with glucose metabolism not only providing essential energy but also offering a variety of metabolic substrates and intermediates that regulate developmental events, influence cell signaling and impact epigenetic modifications. This article emphasizes that future research will focus on regulating maternal metabolic environments and noninvasive metabolic monitoring of embryonic systems, particularly glucose metabolism, with promising opportunities to improve embryo selection and personalized assisted reproductive technologies, ultimately enhancing fertility treatment outcomes.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S100A11 promotes lipid metabolism and activates the apoptosis in polycystic ovary syndrome.","authors":"Xiao Yang, Muzi Li, Zihan Xu, Qi Jiang, Yanbo Du, Hong Lv, Lei Yan","doi":"10.1530/REP-24-0232","DOIUrl":"10.1530/REP-24-0232","url":null,"abstract":"<p><strong>In brief: </strong>Aberrant lipid metabolism and dysregulated apoptosis in granulosa cells (GCs) may contribute to diminished ovarian reserve in patients with polycystic ovary syndrome (PCOS). This article elucidates the pivotal role played by S100A11.</p><p><strong>Abstract: </strong>Apoptosis of ovarian GCs affects the development and maturation of oocyte in PCOS. The objective of our study was to examine the impact of S100A11 on GCs in individuals with polycystic ovary syndrome. We found that the S100A11 level was higher in the ovarian GCs of PCOS patients and ovarian tissue of PCOS mouse models. S100A11 overexpression experiments demonstrated a decrease in the cell proliferation, upregulating the apoptosis and blocking the cell cycle. Immunofluorescence staining showed that S100A11 proteins were mainly located in the nucleus. Integrating the RNA-seq and ChIP-seq, this study found that S100A11 mainly regulated the genetic transcription and lipid metabolism. Furthermore, lipid accumulation and increasing oxidative stress were detected in the S100A11 overexpression group. We also revealed that S100A11 upregulated the p-DRP1 Ser616 to induce the mitochondrial fission. In conclusion, S100A11 upregulated the phospho-DRP1 to activate ovarian GC apoptosis and induced the lipid metabolism and oxidative stress to regulate the follicular reserve in PCOS. Our study provides a functional link between S100A11 expression and apoptosis and lipid metabolism in PCOS, providing new insights into disease mechanisms.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Creatine promotes endometriosis progression by inducing M2 polarization of peritoneal macrophages.","authors":"Si-Man Chen, Yu-Kai Liu, Xiao-Qian Ma, Chun-Yan Wei, Ming-Qing Li, Xiao-Yong Zhu","doi":"10.1530/REP-24-0278","DOIUrl":"10.1530/REP-24-0278","url":null,"abstract":"<p><strong>In brief: </strong>Endometriosis (EM) is a chronic inflammatory disease with unclear pathogenesis, in which peritoneal macrophages play a pivotal role. This study demonstrates that creatine (CR) induces M2 polarization of peritoneal macrophages, promoting angiogenesis, fibrogenesis and lesion progression in EM, offering new insight into potential therapeutic strategies.</p><p><strong>Abstract: </strong>EM is a chronic inflammatory disease characterized by the growth of endometrium-like tissues outside the uterine cavity, with an unclear pathogenesis. The analysis of single-cell sequencing data revealed the pivotal role of peritoneal macrophages in the development of EM. We noted significant CR enrichment and synthesis in peritoneal macrophages of patients with EM compared with women without EM. To further investigate the mechanisms of CR in EM, we performed RNA sequencing and in vitro experiments. We found that CR reprograms M2 polarization by enhancing matrix metalloproteinases and anti-inflammatory cytokines, which are involved in angiogenesis, fibrogenesis, cell adhesion and tissue repair. The coculture of CR-treated macrophages promoted the migration and fibrogenesis of endometrial stromal cells, as well as the angiogenesis of HUVECs in vitro. In summary, this article reveals that CR might polarize M2 macrophages, promoting the initiation, fibrosis and angiogenesis of ectopic endometrial lesions, ultimately resulting in the development of EM. These findings underscore the crucial immunomodulatory role of CR in the pathogenesis of EM, offering a promising target for therapeutic intervention.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of PRICKLE1 leads to subfertility, aberrant extracellular matrix and abnormal myometrial architecture in mice.","authors":"Emily R Roberts, Sornakala Ganeshkumar, Sumedha Gunewardena, Vargheese Chennathukuzhi","doi":"10.1530/REP-24-0344","DOIUrl":"10.1530/REP-24-0344","url":null,"abstract":"<p><strong>In brief: </strong>PRICKLE1, a WNT/planar cell polarity (PCP) protein that is downregulated in uterine leiomyoma, plays an important role in myometrial tissue architecture and extracellular matrix (ECM) deposition. This paper shows that myometrial-specific ablation of the mouse Prickle1 gene results in a uterine leiomyoma phenotype.</p><p><strong>Abstract: </strong>Uterine leiomyomas (ULs) are the most prevalent benign tumors of the female reproductive tract, originating from the myometrium and affecting over 75% of reproductive-age women. Symptoms of UL include pelvic pain, pressure, dysmenorrhea, menorrhagia, anemia and reproductive dysfunction. Currently, there is no effective long-term pharmacotherapy for UL, making them the leading cause of hysterectomies in the United States. The lack of treatment options is attributed to the absence of accurate animal models and a limited understanding of UL pathogenesis. Previous research has shown that the loss of repressor of element 1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) within the myometrium promotes UL pathogenesis. In addition, deletion of Rest in the mouse myometrium leads to a UL phenotype. PRICKLE1, also known as Rest-interacting LIM-domain protein (RILP), is required for nuclear localization of REST and Wnt/PCP signaling, making it a critical target for UL studies. In the context of PCP, smooth muscle cells in UL show abnormal organization, aberrant ECM structure and expression levels, potentially influenced by PRICKLE1 loss. The exact role of PRICKLE1 and Wnt/PCP in UL pathogenesis remains unclear. To explore PRICKLE1's role in UL, we deleted Prickle1 using our myometrial-specific iCre. Our findings demonstrate that Prickle1 loss in the myometrium results in a UL phenotype characterized by altered collagen expression, excessive ECM deposition, aberrant smooth muscle cell organization, increased Esr1 and Pgr expression and dysregulated Wnt/PCP signaling. This novel mouse model serves as a valuable preclinical tool for understanding UL pathogenesis and developing future pharmacotherapies.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ERα phosphorylated at Ser309 participates in regulating luminal environment of efferent ducts and epididymis in mice.","authors":"Jinhua Wei, Pang Cheng, Binfang Ma, Xiao Feng, Junxian Ma, Jie Zhao, Yanqiu Zhao, Zhen Li","doi":"10.1530/REP-24-0109","DOIUrl":"10.1530/REP-24-0109","url":null,"abstract":"<p><strong>In brief: </strong>The epididymis plays an important role in sperm maturation and male fertility. This study provides evidence that estrogen receptor alpha (ERα/ESR1) phosphorylated at Ser309 is essential for efferent duct fluid reabsorption and epididymal luminal acidification to create and maintain the optimal luminal milieu in mice.</p><p><strong>Abstract: </strong>ERα (ESR1) plays an important role in male reproduction and fertility. Its activity is modulated by phosphorylation of multiple amino acid residues. The ERα phosphorylated at serine 305 (S305) in human cells (homologous with serine 309 in mice) induces ligand-independent ERα activity. Here, we studied the effect of ERα phosphorylation at S309 on the reproductive function of male mice. ERα309 (p.S309A, ERαS309A) knock-in (KI) mice were generated by homologous recombination in mouse embryonic stem cells. The ERαS309A KI males were subfertile with decreased sperm motility, dilated lumen and thinned epithelium of efferent ducts. Ultrastructural observation showed that the area of endocytic vesicles and lysosomes in the non-ciliated cells and the number of cilia in the ciliated cells were significantly reduced in the efferent ducts of the ERαS309A KI mice. The pH value of the epididymal fluid was significantly higher in all regions of epididymis in the ERαS309A KI mice. Moreover, the expression of aquaporin 9 (AQP9) in the efferent ducts and carbonic anhydrase XII (CAR12) in the epididymis was decreased in ERαS309A KI mice. The results indicate that the ERα phosphorylated at Ser309 participates in maintaining the unique luminal milieu by regulating the expression of critical regulators of fluid/ion transport in the efferent ducts and epididymis.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142954137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of clinical artificial oocyte activation protocols on mouse egg activation and embryo development.","authors":"Lucas N González, Valeria Sulzyk, Patricia S Cuasnicú, Débora J Cohen","doi":"10.1530/REP-24-0387","DOIUrl":"10.1530/REP-24-0387","url":null,"abstract":"<p><strong>In brief: </strong>Artificial oocyte activation (AOA) with Ca2+ ionophores is a valuable tool in assisted reproduction but may affect cellular events critical for embryo development. This study shows the impact of different AOA protocols on embryonic development efficiency and meiotic progression.</p><p><strong>Abstract: </strong>AOA with Ca2+ ionophores is an experimental procedure that benefits patients who fail to obtain fertilized eggs. However, the impact of non-physiological Ca2+ increases on cellular events involved in the egg-embryo transition and early development remains poorly understood. Using the mouse model, this study compares common Ca2+ ionophore protocols applied in clinical practice - one or two exposures to A23187 or a single exposure to ionomycin - focusing on embryonic development and cellular events associated with egg activation. All groups of ionophore-activated eggs exhibit lower levels of first mitotic division compared to those activated by spermatozoa or SrCl2, attributable to variations in Ca2+ dynamics during activation. At the cellular level, these eggs presented defects in spindle morphology and chromosome segregation during meiosis progression, associated with lower levels of cytoplasmic ATP, without changes in reactive oxygen species. These findings highlight the importance of optimizing Ca2+ management in AOA protocols.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}