Pub Date : 2025-11-26DOI: 10.1016/j.repbio.2025.101166
Mehmet Can Nacar , Recai Aci̇ , Şengül Tural , Serbülent Yi̇ği̇t
This study aimed to investigate the association between the SOD1 gene I>D polymorphism, a key component of the antioxidant defense system, and polycystic ovary syndrome (PCOS), as well as to evaluate the potential effects of this genetic variation on genotypic distribution and metabolic parameters. A total of 100 PCOS patients and 135 healthy controls were included, and genomic DNA extracted from peripheral blood was analyzed for the SOD1 I>D polymorphism using conventional PCR, while clinical and biochemical parameters such as body mass index (BMI), insulin levels, HOMA-IR, FSH, LH, and other hormone levels were assessed. The ID genotype was found to be less frequent in the PCOS group compared to controls, with borderline statistical significance (p = 0.050; OR = 0.57), and was significantly less common in PCOS patients with a positive family history (p = 0.013), suggesting a potential protective effect, while correlations were observed between the ID genotype and markers of insulin resistance, though no significant differences were detected in allele frequencies. These findings indicate that the SOD1 gene I>D polymorphism may influence both susceptibility and metabolic characteristics of PCOS, supporting the role of oxidative stress in its pathogenesis and emphasizing the need for further functional and large-scale studies to confirm these associations.
{"title":"Genotypic and metabolic impact of the SOD1 I>D polymorphism in polycystic ovary syndrome","authors":"Mehmet Can Nacar , Recai Aci̇ , Şengül Tural , Serbülent Yi̇ği̇t","doi":"10.1016/j.repbio.2025.101166","DOIUrl":"10.1016/j.repbio.2025.101166","url":null,"abstract":"<div><div>This study aimed to investigate the association between the SOD1 gene I>D polymorphism, a key component of the antioxidant defense system, and polycystic ovary syndrome (PCOS), as well as to evaluate the potential effects of this genetic variation on genotypic distribution and metabolic parameters. A total of 100 PCOS patients and 135 healthy controls were included, and genomic DNA extracted from peripheral blood was analyzed for the SOD1 I>D polymorphism using conventional PCR, while clinical and biochemical parameters such as body mass index (BMI), insulin levels, HOMA-IR, FSH, LH, and other hormone levels were assessed. The ID genotype was found to be less frequent in the PCOS group compared to controls, with borderline statistical significance (p = 0.050; OR = 0.57), and was significantly less common in PCOS patients with a positive family history (p = 0.013), suggesting a potential protective effect, while correlations were observed between the ID genotype and markers of insulin resistance, though no significant differences were detected in allele frequencies. These findings indicate that the SOD1 gene I>D polymorphism may influence both susceptibility and metabolic characteristics of PCOS, supporting the role of oxidative stress in its pathogenesis and emphasizing the need for further functional and large-scale studies to confirm these associations.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"26 1","pages":"Article 101166"},"PeriodicalIF":2.5,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614579","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}
Pub Date : 2025-11-25DOI: 10.1016/j.repbio.2025.101167
Huamei Ju , Ziliang Geng , Binyan Chen , Yuwei Shang , Xia Chen , Danni Wang , Wenbin Wang , Huiting Sun , Yichao Shi , Jiajun Yu
The heterotrimeric complex serine-threonine protein phosphatase 2 A (PP2A) is integral to the regulation of essential cellular processes. It is particularly crucial in spermatogenesis, where it is indispensable for meiosis, mitosis, sperm capacitation, and apoptosis. Previous research has concentrated on the knockdown of the catalytic subunit of PP2A, PPP2CA, in germ cells using Ddx4-Cre, resulting in male mouse sterility, disrupted meiotic recombination, and meiotic arrest of spermatocytes. To further elucidate the role of PP2A in spermatogenesis, we performed transcriptomic and proteomic sequencing analyses on the testes of knockout and control mice. A nine-quadrant map was developed to depict the differential expression of genes and proteins. Our analyses identified 1732 differentially expressed genes, which exhibited a strong positive correlation with the trends in differential protein expression. Gene Ontology (GO) enrichment analysis indicated a significant downregulation of genes involved in spermatogenesis, sperm cell development, and sperm cell differentiation. Furthermore, KEGG enrichment analysis revealed a notable enrichment of differentially expressed genes within the ubiquitin-mediated proteolysis pathway. In knockout mouse testicular tissue, testicular expression of the ubiquitin-related gene, UBE2K, was markedly downregulated, which was associated with the accumulation of histone H3, upregulation of the methyltransferase SETDB1, and increased levels of H3K9me3. Similarly, knockdown of Ppp2ca in GC2 cells resulted in decreased UBE2K expression, histone H3 accumulation, SETDB1 upregulation, and elevated H3K9me3 levels, consistent with mirroring the phenotype observed in the knockout mice. Notably, the ubiquitin-related gene UBE2K was identified as a significant outlier in the nine-quadrant map, and real-time quantitative PCR confirmed that UBE2K transcript levels were significantly reduced in knockout mice compared to wild-type controls. These findings suggest that PP2A may regulate histon.
异三聚体复合体丝氨酸-苏氨酸蛋白磷酸酶2 A （PP2A）是必不可少的细胞过程的调节。它在精子发生中尤其重要，在那里它对减数分裂、有丝分裂、精子获能和细胞凋亡是必不可少的。先前的研究主要集中在使用Ddx4-Cre敲除生殖细胞中PP2A的催化亚基PPP2CA，导致雄性小鼠不育、减数分裂重组中断和精母细胞减数分裂停滞。为了进一步阐明PP2A在精子发生中的作用，我们对敲除小鼠和对照小鼠的睾丸进行了转录组学和蛋白质组学测序分析。一个九象限的图谱被用来描绘基因和蛋白质的差异表达。我们的分析确定了1732个差异表达基因，这些基因与差异蛋白表达趋势表现出很强的正相关。基因本体（GO）富集分析表明，参与精子发生、精子细胞发育和精子细胞分化的基因显著下调。此外，KEGG富集分析显示，在泛素介导的蛋白水解途径中，差异表达基因显著富集。在敲除小鼠睾丸组织中，睾丸中泛素相关基因UBE2K的表达明显下调，这与组蛋白H3的积累、甲基转移酶SETDB1的上调以及H3K9me3水平的升高有关。同样，在GC2细胞中敲低Ppp2ca导致UBE2K表达降低，组蛋白H3积累，SETDB1上调，H3K9me3水平升高，与敲除小鼠的表型一致。值得注意的是，泛素相关基因UBE2K在九象限图谱中被鉴定为显著异常值，实时定量PCR证实，与野生型对照相比，敲除小鼠的UBE2K转录水平显著降低。这些发现表明PP2A可能调节组蛋白。
{"title":"Mechanism of PP2A affecting ubiquitination pathway in spermatogenesis","authors":"Huamei Ju , Ziliang Geng , Binyan Chen , Yuwei Shang , Xia Chen , Danni Wang , Wenbin Wang , Huiting Sun , Yichao Shi , Jiajun Yu","doi":"10.1016/j.repbio.2025.101167","DOIUrl":"10.1016/j.repbio.2025.101167","url":null,"abstract":"<div><div>The heterotrimeric complex serine-threonine protein phosphatase 2 A (PP2A) is integral to the regulation of essential cellular processes. It is particularly crucial in spermatogenesis, where it is indispensable for meiosis, mitosis, sperm capacitation, and apoptosis. Previous research has concentrated on the knockdown of the catalytic subunit of PP2A, PPP2CA, in germ cells using Ddx4-Cre, resulting in male mouse sterility, disrupted meiotic recombination, and meiotic arrest of spermatocytes. To further elucidate the role of PP2A in spermatogenesis, we performed transcriptomic and proteomic sequencing analyses on the testes of knockout and control mice. A nine-quadrant map was developed to depict the differential expression of genes and proteins. Our analyses identified 1732 differentially expressed genes, which exhibited a strong positive correlation with the trends in differential protein expression. Gene Ontology (GO) enrichment analysis indicated a significant downregulation of genes involved in spermatogenesis, sperm cell development, and sperm cell differentiation. Furthermore, KEGG enrichment analysis revealed a notable enrichment of differentially expressed genes within the ubiquitin-mediated proteolysis pathway. In knockout mouse testicular tissue, testicular expression of the ubiquitin-related gene, UBE2K, was markedly downregulated, which was associated with the accumulation of histone H3, upregulation of the methyltransferase SETDB1, and increased levels of H3K9me3. Similarly, knockdown of Ppp2ca in GC2 cells resulted in decreased UBE2K expression, histone H3 accumulation, SETDB1 upregulation, and elevated H3K9me3 levels, consistent with mirroring the phenotype observed in the knockout mice. Notably, the ubiquitin-related gene UBE2K was identified as a significant outlier in the nine-quadrant map, and real-time quantitative PCR confirmed that UBE2K transcript levels were significantly reduced in knockout mice compared to wild-type controls. These findings suggest that PP2A may regulate histon.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"26 1","pages":"Article 101167"},"PeriodicalIF":2.5,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614450","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}
Pub Date : 2025-11-21DOI: 10.1016/j.repbio.2025.101103
José Anderson da Silva Gomes , Renan Gabriel da Silva Ferreira , Jennyfer Martins de Carvalho , Maria Luísa Figueira de Oliveira , Rubem Carlos Araújo Guedes , Elba Verônica Matoso Maciel de Carvalho , Leucio Duarte Vieira Filho , Bruno Mendes Tenorio , Fernanda das Chagas Angelo Mendes Tenorio
The aim of the present study was to investigate the activity of exogenous melatonin as a potential agent in reversing testicular structural damage induced by early weaning. For this purpose, Wistar rats were used and divided into four experimental groups: control; early weaning; early weaning treated with melatonin in a daily dose 10 mg/kg of body weight; and early weaning treated with a vehicle composed of ethanol and saline solution. Except for the control group, all animals were weaned on the 16th day after birth. Body weight was measured weekly, and euthanasia was performed on day 51. The testes were weighed and collected for histopathological, morphometric, immunohistochemical, and oxidative stress analyses, while serum was collected for biochemical and hormonal analyses. At the end of the experiment, the early weaning group exhibited an increase in body mass, as well as structural alterations, including a reduction in the diameter and height of the seminiferous tubule epithelium, along with atrophy, vacuolization, and degeneration of germ cells. This group also showed lower production of pachytene spermatocytes, Sertoli cells, and Leydig cells, increased oxidative stress, decreased testosterone concentration, an adverse lipid profile, and reduced PCNA labeling. In contrast, the group treated with melatonin demonstrated improvement in these parameters when compared to early weaning group. These findings suggest that melatonin exerts a restorative role in testicular tissue.
{"title":"Effect of exogenous melatonin on the testes of Wistar rats undergoing early weaning","authors":"José Anderson da Silva Gomes , Renan Gabriel da Silva Ferreira , Jennyfer Martins de Carvalho , Maria Luísa Figueira de Oliveira , Rubem Carlos Araújo Guedes , Elba Verônica Matoso Maciel de Carvalho , Leucio Duarte Vieira Filho , Bruno Mendes Tenorio , Fernanda das Chagas Angelo Mendes Tenorio","doi":"10.1016/j.repbio.2025.101103","DOIUrl":"10.1016/j.repbio.2025.101103","url":null,"abstract":"<div><div>The aim of the present study was to investigate the activity of exogenous melatonin as a potential agent in reversing testicular structural damage induced by early weaning. For this purpose, Wistar rats were used and divided into four experimental groups: control; early weaning; early weaning treated with melatonin in a daily dose 10 mg/kg of body weight; and early weaning treated with a vehicle composed of ethanol and saline solution. Except for the control group, all animals were weaned on the 16th day after birth. Body weight was measured weekly, and euthanasia was performed on day 51. The testes were weighed and collected for histopathological, morphometric, immunohistochemical, and oxidative stress analyses, while serum was collected for biochemical and hormonal analyses. At the end of the experiment, the early weaning group exhibited an increase in body mass, as well as structural alterations, including a reduction in the diameter and height of the seminiferous tubule epithelium, along with atrophy, vacuolization, and degeneration of germ cells. This group also showed lower production of pachytene spermatocytes, Sertoli cells, and Leydig cells, increased oxidative stress, decreased testosterone concentration, an adverse lipid profile, and reduced PCNA labeling. In contrast, the group treated with melatonin demonstrated improvement in these parameters when compared to early weaning group. These findings suggest that melatonin exerts a restorative role in testicular tissue.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"26 1","pages":"Article 101103"},"PeriodicalIF":2.5,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568961","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}
We aimed to develop prediction models estimating (1) the probability of obtaining a target number of euploid embryos per individual and (2) the probability of euploidy at the embryo level using data from preimplantation genetic testing for aneuploidy (PGT-A). This retrospective observational study included 664 individuals who underwent PGT-A between March 2020 and October 2024, totaling 5539 biopsied embryos (23.2 % euploid). Among them, 153 had no euploid embryos and 511 had at least one. Four models were developed: Models 1-A, 1-B, and 1-C predicted the probability of obtaining ≥ 1, ≥ 2, and ≥ 3 euploid embryos, respectively. Model 2 predicted the probability of euploidy per embryo. Multivariate logistic regression was used for individual-level models (1-A to 1-C), and a generalized estimating equation was applied for Model 2. Predictors included maternal age at retrieval, number of biopsied embryos, and embryo morphology. Area under the receiver operating characteristic curve (AUC) was used to examine the discriminative ability of models. Internal validation was performed using 10-fold cross-validation. Decision curve analysis assessed clinical utility. Models 1-A, 1-B, and 1-C demonstrated good discrimination (AUCs: 0.85–0.87), while Model 2 showed fair discrimination (AUC: 0.77). Decision curve analysis supported the clinical utility of all models at wide range of thresholds probabilties. The individual-level prediction models demonstrated good discriminative ability, while the embryo-level model showed fair discriminative ability. All models demonstrated potential clinical utility in supporting embryo selection.
{"title":"Prediction of euploidy and probability of obtaining target number of euploid embryos through preimplantation genetic testing for aneuploidy","authors":"Kazuma Onishi , Daichi Inoue , Yuta Kida , Masae Kojima , Chiharu Ishida , Takahiro Suzuki , Shuhei Kamada , Noritaka Fukunaga , Yoshimasa Asada","doi":"10.1016/j.repbio.2025.101104","DOIUrl":"10.1016/j.repbio.2025.101104","url":null,"abstract":"<div><div>We aimed to develop prediction models estimating (1) the probability of obtaining a target number of euploid embryos per individual and (2) the probability of euploidy at the embryo level using data from preimplantation genetic testing for aneuploidy (PGT-A). This retrospective observational study included 664 individuals who underwent PGT-A between March 2020 and October 2024, totaling 5539 biopsied embryos (23.2 % euploid). Among them, 153 had no euploid embryos and 511 had at least one. Four models were developed: Models 1-A, 1-B, and 1-C predicted the probability of obtaining ≥ 1, ≥ 2, and ≥ 3 euploid embryos, respectively. Model 2 predicted the probability of euploidy per embryo. Multivariate logistic regression was used for individual-level models (1-A to 1-C), and a generalized estimating equation was applied for Model 2. Predictors included maternal age at retrieval, number of biopsied embryos, and embryo morphology. Area under the receiver operating characteristic curve (AUC) was used to examine the discriminative ability of models. Internal validation was performed using 10-fold cross-validation. Decision curve analysis assessed clinical utility. Models 1-A, 1-B, and 1-C demonstrated good discrimination (AUCs: 0.85–0.87), while Model 2 showed fair discrimination (AUC: 0.77). Decision curve analysis supported the clinical utility of all models at wide range of thresholds probabilties. The individual-level prediction models demonstrated good discriminative ability, while the embryo-level model showed fair discriminative ability. All models demonstrated potential clinical utility in supporting embryo selection.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"26 1","pages":"Article 101104"},"PeriodicalIF":2.5,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568962","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}
Pub Date : 2025-11-20DOI: 10.1016/j.repbio.2025.101096
Chenming Zhang , Xiaofei Han , Yifei Wang , Ruimin Ma , Sicheng Ma , Wenbang Liu , Zhe Chang , Zixue Sun
Polystyrene microplastics (PS-MPs) are extensively utilized in plastic goods worldwide. The ingestion of PS-MPs has resulted in a high rate of DNA fragmentation index (DFI), which can potentially result in infertility and recurrent spontaneous abortion. This study established and characterized a mouse model of polystyrene microplastic (PS-MP)-induced sperm DNA damage (DnaD), and concurrently analyzed the associated transcriptomic and proteomic profiles. Over a period of 60 days, male mice assigned to the PS group were given PS-MPs at a dose of 1 mg/kg/d while the control group was administered an equivalent volume of normal saline. Sperm DNA Fragmentation Index (DFI) was then assessed using the Sperm Chromatin Structure Assay (SCSA).The testis was examined using RNA-seq and data-independent acquisition (DIA) to detect the patterns of mRNA and protein expression. The PS group exhibited an significant increase in the sperm DFI. Compared with the control group, 874 differentially expressed genes (DEGs) and 164 differentially expressed proteins (DEPs) were identified in the PS group. These included Agt, Gstt1, Fetub, Akr1c12, Eln, Gaa, Ppic and Ltbp2. The PI3K/Akt and metabolic pathways exhibited significant enrichment of these genes. After a 60-day period of intragastric injection, our findings indicated that the administration of PS-MPs at a 1 mg/kg/d dosage can lead to DnaD in the sperm of male mice. The metabolic and PI3K/Akt signaling pathways could be associated with the reproductive toxicity of PS-MPs.
Summary sentence
The intake of PS-MPs mainly reduces DFI in mice via the metabolic and PI3K/Akt signaling pathways.
{"title":"The mouse model of induced sperm DNA damage caused by polystyrene microplastics exhibited distinct transcriptomic and proteomic features","authors":"Chenming Zhang , Xiaofei Han , Yifei Wang , Ruimin Ma , Sicheng Ma , Wenbang Liu , Zhe Chang , Zixue Sun","doi":"10.1016/j.repbio.2025.101096","DOIUrl":"10.1016/j.repbio.2025.101096","url":null,"abstract":"<div><div>Polystyrene microplastics (PS-MPs) are extensively utilized in plastic goods worldwide. The ingestion of PS-MPs has resulted in a high rate of DNA fragmentation index (DFI), which can potentially result in infertility and recurrent spontaneous abortion. This study established and characterized a mouse model of polystyrene microplastic (PS-MP)-induced sperm DNA damage (DnaD), and concurrently analyzed the associated transcriptomic and proteomic profiles. Over a period of 60 days, male mice assigned to the PS group were given PS-MPs at a dose of 1 mg/kg/d while the control group was administered an equivalent volume of normal saline. Sperm DNA Fragmentation Index (DFI) was then assessed using the Sperm Chromatin Structure Assay (SCSA).The testis was examined using RNA-seq and data-independent acquisition (DIA) to detect the patterns of mRNA and protein expression. The PS group exhibited an significant increase in the sperm DFI. Compared with the control group, 874 differentially expressed genes (DEGs) and 164 differentially expressed proteins (DEPs) were identified in the PS group. These included Agt, Gstt1, Fetub, Akr1c12, Eln, Gaa, Ppic and Ltbp2. The PI3K/Akt and metabolic pathways exhibited significant enrichment of these genes. After a 60-day period of intragastric injection, our findings indicated that the administration of PS-MPs at a 1 mg/kg/d dosage can lead to DnaD in the sperm of male mice. The metabolic and PI3K/Akt signaling pathways could be associated with the reproductive toxicity of PS-MPs.</div></div><div><h3>Summary sentence</h3><div>The intake of PS-MPs mainly reduces DFI in mice via the metabolic and PI3K/Akt signaling pathways.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"26 1","pages":"Article 101096"},"PeriodicalIF":2.5,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568960","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}
Pub Date : 2025-11-20DOI: 10.1016/j.repbio.2025.101100
Rossella Fucci , Irene Oliva , Arianna Marcellini , Francesca Rizzello , Laura Badolato , Denise De Angelis , Paolo Evangelisti , Elisabetta Baldi , Asia Iserani , Patrizia Falcone , Maria Elisabetta Coccia
To date, the Gardner Grading System remains the gold standard for the conventional evaluation of blastocysts. However, the use of Time-lapse technology in Assisted Reproductive Technologies (ART) cycles provides a dynamic, morphokinetic assessment that complements traditional morphological evaluation, as vitrification and subsequent warming process may induce morphological and biochemical variations in blastocysts. After warming, 203 blastocysts, obtained from homologous ART cycles, were cultured in EmbryoScope to evaluate their morphokinetic modifications using Time-Lapse Technology (TLT). (I) The degree of trophectoderm expansion at insertion into the incubator (t0 exp), (II) the first signal of trophectoderm re-expansion (t first exp), and (III) the degree of expansion and morphology at two hours (t2h exp, t2h grad) were recorded. Statistical analysis was performed by SPSS version 29.0 and relations between I, II, III parameters and beta-human Chorionic Gonadotropin (beta-hCG) outcome, heartbeat, and live birth were assessed.
Results
Showed that t first exp was significantly associated with beta-hCG levels, heartbeat, and live birth outcomes. Additionally, blastocysts achieving complete re-expansion within two hours and presented optimal morphology exhibited a higher likelihood of successful implantation. Early biomarkers were identified through morphokinetic parameters derived from Time-Lapse technology, and pregnancy outcome prediction was improved by the combination of morphological evaluation with post-warming kinetic assessments.
迄今为止，加德纳分级系统仍然是传统囊胚评估的金标准。然而，在辅助生殖技术（ART）周期中使用延时技术提供了一种动态的形态动力学评估，补充了传统的形态学评估，因为玻璃化和随后的升温过程可能会诱导囊胚的形态和生化变化。加热后，从同源ART周期中获得203个囊胚，在EmbryoScope中培养，使用延时技术（Time-Lapse Technology， TLT）评估其形态动力学改变。(I)记录滋养外胚层插入培养箱时的膨胀程度（第0 exp）， （II）滋养外胚层再次膨胀的第一次信号（第t first exp）， （III） 2h时的膨胀程度和形态（第2h exp，第2h grad）。采用SPSS 29.0进行统计分析，评估I、II、III参数与β -人绒毛膜促性腺激素（β - hcg）结局、心跳、活产之间的关系。结果表明，t first exp与β - hcg水平、心跳和活产结局显著相关。此外，囊胚在2小时内完全再膨胀并呈现最佳形态，表明植入成功的可能性更高。通过Time-Lapse技术获得的形态动力学参数来识别早期生物标志物，并通过形态评估和升温后动力学评估相结合来改善妊娠结局预测。
{"title":"Morphokinetic assessment of the blastocyst’s trophectoderm re-expansion post-warming: predictive markers for clinical pregnancy in ART","authors":"Rossella Fucci , Irene Oliva , Arianna Marcellini , Francesca Rizzello , Laura Badolato , Denise De Angelis , Paolo Evangelisti , Elisabetta Baldi , Asia Iserani , Patrizia Falcone , Maria Elisabetta Coccia","doi":"10.1016/j.repbio.2025.101100","DOIUrl":"10.1016/j.repbio.2025.101100","url":null,"abstract":"<div><div>To date, the Gardner Grading System remains the gold standard for the conventional evaluation of blastocysts. However, the use of Time-lapse technology in Assisted Reproductive Technologies (ART) cycles provides a dynamic, morphokinetic assessment that complements traditional morphological evaluation, as vitrification and subsequent warming process may induce morphological and biochemical variations in blastocysts. After warming, 203 blastocysts, obtained from homologous ART cycles, were cultured in EmbryoScope to evaluate their morphokinetic modifications using Time-Lapse Technology (TLT). (I) The degree of trophectoderm expansion at insertion into the incubator (t0 exp), (II) the first signal of trophectoderm re-expansion (t first exp), and (III) the degree of expansion and morphology at two hours (t2h exp, t2h grad) were recorded. Statistical analysis was performed by SPSS version 29.0 and relations between I, II, III parameters and beta-human Chorionic Gonadotropin (beta-hCG) outcome, heartbeat, and live birth were assessed.</div></div><div><h3>Results</h3><div>Showed that t first exp was significantly associated with beta-hCG levels, heartbeat, and live birth outcomes. Additionally, blastocysts achieving complete re-expansion within two hours and presented optimal morphology exhibited a higher likelihood of successful implantation. Early biomarkers were identified through morphokinetic parameters derived from Time-Lapse technology, and pregnancy outcome prediction was improved by the combination of morphological evaluation with post-warming kinetic assessments.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"26 1","pages":"Article 101100"},"PeriodicalIF":2.5,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568963","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}
Pub Date : 2025-11-14DOI: 10.1016/j.repbio.2025.101102
Xu Li , Shuhong Tang , Yinwei Zheng , Ruiguo Zhao , Feifan Xu , Naerhulan Ayiken , Guangdong Hu , Yanping Wang , Weibin Zeng
Phloretin, a natural dihydrochalcone flavonoid, is recognized for its potent antioxidant, anti-apoptotic, and anti-inflammatory properties. This study investigated the effects of phloretin on the in vitro maturation (IVM) of sheep oocytes and subsequent early embryonic development. Treatment with 5 μmol/L phloretin significantly improved the rates of oocyte maturation, cleavage, and blastocyst formation compared to the control group. This treatment also significantly increased intracellular glutathione (GSH) levels and mitochondrial membrane potential (ΔΨm), while reducing reactive oxygen species (ROS) levels. Furthermore, the treatment up-regulated the expression of key antioxidant genes (CAT, SOD2, GPX3) and the follicular development factor gene BMP15. Similarly, supplementing the early embryo culture medium with 5 μmol/L phloretin elevated GSH levels and ΔΨm, and reduced ROS levels in morulae. It also up-regulated the expression of the antioxidant genes CAT, GPX3, and SOD2. Moreover, the treatment enhanced the expression of development-related genes (P53 and OCT4) and significantly decreased the pro-apoptotic Bax/Bcl-2 ratio. In conclusion, phloretin enhances the efficiency of sheep oocyte IVM and early embryonic development by bolstering antioxidant defenses, inhibiting apoptosis, and promoting development. These findings provide a foundation for optimizing in vitro embryo production (IVP) protocols in sheep.
{"title":"Phloretin enhances the efficiency of sheep oocyte IVM and early embryonic development by bolstering antioxidant defenses, inhibiting apoptosis, and promoting development","authors":"Xu Li , Shuhong Tang , Yinwei Zheng , Ruiguo Zhao , Feifan Xu , Naerhulan Ayiken , Guangdong Hu , Yanping Wang , Weibin Zeng","doi":"10.1016/j.repbio.2025.101102","DOIUrl":"10.1016/j.repbio.2025.101102","url":null,"abstract":"<div><div>Phloretin, a natural dihydrochalcone flavonoid, is recognized for its potent antioxidant, anti-apoptotic, and anti-inflammatory properties. This study investigated the effects of phloretin on the in vitro maturation (IVM) of sheep oocytes and subsequent early embryonic development. Treatment with 5 μmol/L phloretin significantly improved the rates of oocyte maturation, cleavage, and blastocyst formation compared to the control group. This treatment also significantly increased intracellular glutathione (GSH) levels and mitochondrial membrane potential (ΔΨm), while reducing reactive oxygen species (ROS) levels. Furthermore, the treatment up-regulated the expression of key antioxidant genes (CAT, SOD2, GPX3) and the follicular development factor gene BMP15. Similarly, supplementing the early embryo culture medium with 5 μmol/L phloretin elevated GSH levels and ΔΨm, and reduced ROS levels in morulae. It also up-regulated the expression of the antioxidant genes CAT, GPX3, and SOD2. Moreover, the treatment enhanced the expression of development-related genes (P53 and OCT4) and significantly decreased the pro-apoptotic Bax/Bcl-2 ratio. In conclusion, phloretin enhances the efficiency of sheep oocyte IVM and early embryonic development by bolstering antioxidant defenses, inhibiting apoptosis, and promoting development. These findings provide a foundation for optimizing in vitro embryo production (IVP) protocols in sheep.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"26 1","pages":"Article 101102"},"PeriodicalIF":2.5,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517484","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}
Annatto (Bixa orellana) carotenoids have antioxidant potential, but effects on placental biology and antioxidant parameters in ewes are unclear. We tested whether dietary annatto concentrate (ANC) in late gestation modulates immediate-postpartum blood oxidative markers and placental gene abundance. Thirty ewes were stratified by expected litter size (single/twin) and randomized within stratum to 0 %, 0.5 %, or 1.0 % ANC (dry-matter basis) from gestational day 100. ANC was a powdered concentrate, premixed into feed (1.5 % BW) and offered individually to ensure full intake. At lambing, we recorded maternal/neonatal descriptors (ewe weights, gestational length, time to placental expulsion, and lamb birth weight interpreted with litter size and sex), collected blood for FRAP, TBARS–MDA, H₂O₂, SOD, GPx, CAT, and –SH, and sampled placenta (cotyledon and intercotyledonary tissue) aseptically and froze it for RT-qPCR of VEGF-A, FGF-2, PAG1, GPX1, GSR, CAT, and SOD2. ANC produced marker-specific blood adjustments: lower H₂O₂ at 1.0 %, higher GPx in supplemented ewes, and lower –SH at 0.5 %, whereas FRAP, SOD, MDA, and CAT were unchanged. In placenta, cotyledonary FGF-2 showed higher relative abundance at 0.5 %, with no differences for VEGF-A, PAG1, GPX1, GSR, CAT, or SOD2 in either tissue. Ewe weights, gestational length, and time to placental expulsion were similar among groups; lamb birth weight showed no main effect of ANC. These results indicate that, in late gestation, ANC selectively increased the relative abundance of cotyledonary FGF-2 at 0.5 % and modulated peroxide handling in blood, supporting its use as a nutritional tool for antioxidant support near parturition.
{"title":"Annatto concentrate supplementation improves systemic redox balance and modulates placental FGF-2 expression in ewes","authors":"Leonardo Lima Salata , Calie Castilho , Isabella Guartieri da Silva , Leticia Jalloul Guimarães , Isabella Pereira Azoia , Ines Cristina Giometti , Dionísio Pedro Lopes Kuhn Pinheiro , Alexandre Martins Olivete , Marilice Zundt","doi":"10.1016/j.repbio.2025.101099","DOIUrl":"10.1016/j.repbio.2025.101099","url":null,"abstract":"<div><div>Annatto (<em>Bixa orellana</em>) carotenoids have antioxidant potential, but effects on placental biology and antioxidant parameters in ewes are unclear. We tested whether dietary annatto concentrate (ANC) in late gestation modulates immediate-postpartum blood oxidative markers and placental gene abundance. Thirty ewes were stratified by expected litter size (single/twin) and randomized within stratum to 0 %, 0.5 %, or 1.0 % ANC (dry-matter basis) from gestational day 100. ANC was a powdered concentrate, premixed into feed (1.5 % BW) and offered individually to ensure full intake. At lambing, we recorded maternal/neonatal descriptors (ewe weights, gestational length, time to placental expulsion, and lamb birth weight interpreted with litter size and sex), collected blood for FRAP, TBARS–MDA, H₂O₂, SOD, GPx, <em>CAT</em>, and –SH, and sampled placenta (cotyledon and intercotyledonary tissue) aseptically and froze it for RT-qPCR of <em>VEGF-A</em>, <em>FGF-2</em>, <em>PAG1</em>, <em>GPX1</em>, <em>GSR</em>, <em>CAT</em>, and <em>SOD2</em>. ANC produced marker-specific blood adjustments: lower H₂O₂ at 1.0 %, higher GPx in supplemented ewes, and lower –SH at 0.5 %, whereas FRAP, SOD, MDA, and <em>CAT</em> were unchanged. In placenta, cotyledonary <em>FGF-2</em> showed higher relative abundance at 0.5 %, with no differences for <em>VEGF-A</em>, <em>PAG1</em>, <em>GPX1</em>, <em>GSR</em>, <em>CAT</em>, or <em>SOD2</em> in either tissue. Ewe weights, gestational length, and time to placental expulsion were similar among groups; lamb birth weight showed no main effect of ANC. These results indicate that, in late gestation, ANC selectively increased the relative abundance of cotyledonary <em>FGF-2</em> at 0.5 % and modulated peroxide handling in blood, supporting its use as a nutritional tool for antioxidant support near parturition.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"26 1","pages":"Article 101099"},"PeriodicalIF":2.5,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517485","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}
Pub Date : 2025-11-12DOI: 10.1016/j.repbio.2025.101098
Islam Ahmed Abdelmawgood , Dina M.M. Kotb , Ahmed Ezzat Mostafa , Bahaa Sharaf , Sohaib Ali Ramadan , Seif Isamil , Ali Moataz , Mariam Abdelghany , Donia Mohamed Hussien , Michael Ibrahim Boushra
Endometritis is the inflammation of the endometrial lining, frequently linked to pelvic pain. Endometritis is significantly associated with postpartum problems, including infertility. Programmed cell death (PCD) is a genetically regulated mechanism of autonomic and regulated cell death that preserves homeostasis and promotes development. PCD, which includes apoptosis, pyroptosis, autophagy, ferroptosis, and necroptosis, is essential in the pathogenesis of reproductive diseases, including endometritis. Despite the limited study on PCD in endometritis, it is essential to identify important molecules and comprehend their regulatory functions for effective disease prevention and management. This review delineates the different types of PCD and their interactions in endometritis. It also evaluates the progress in PCD research pertaining to endometritis. The objective is to create a basis for subsequent investigations into the function and interaction of PCD in endometritis. We anticipate that this study will facilitate the exploration of novel PCD targets for endometritis treatment, hence encouraging comprehensive research.
{"title":"Emerging role and interplay of programmed cell death in endometritis: Insights into mechanisms and therapeutic targets","authors":"Islam Ahmed Abdelmawgood , Dina M.M. Kotb , Ahmed Ezzat Mostafa , Bahaa Sharaf , Sohaib Ali Ramadan , Seif Isamil , Ali Moataz , Mariam Abdelghany , Donia Mohamed Hussien , Michael Ibrahim Boushra","doi":"10.1016/j.repbio.2025.101098","DOIUrl":"10.1016/j.repbio.2025.101098","url":null,"abstract":"<div><div>Endometritis is the inflammation of the endometrial lining, frequently linked to pelvic pain. Endometritis is significantly associated with postpartum problems, including infertility. Programmed cell death (PCD) is a genetically regulated mechanism of autonomic and regulated cell death that preserves homeostasis and promotes development. PCD, which includes apoptosis, pyroptosis, autophagy, ferroptosis, and necroptosis, is essential in the pathogenesis of reproductive diseases, including endometritis. Despite the limited study on PCD in endometritis, it is essential to identify important molecules and comprehend their regulatory functions for effective disease prevention and management. This review delineates the different types of PCD and their interactions in endometritis. It also evaluates the progress in PCD research pertaining to endometritis. The objective is to create a basis for subsequent investigations into the function and interaction of PCD in endometritis. We anticipate that this study will facilitate the exploration of novel PCD targets for endometritis treatment, hence encouraging comprehensive research.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"26 1","pages":"Article 101098"},"PeriodicalIF":2.5,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145514598","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}
Pub Date : 2025-11-11DOI: 10.1016/j.repbio.2025.101101
Iara Magalhães Ribeiro , Renner Philipe Rodrigues Carvalho , Arabela Guedes de Azevedo Viana , Camilo Jose Ramirez-Lopez , Tayná Bolsam da Silva , Mariana Machado-Neves
The overpopulation of free-roaming animals, particularly dogs and cats, poses a significant global public health concern, contributing to socioeconomic, ecological, political, and ethical issues. These animals reproduce freely, increasing the risk of zoonotic disease transmission, wildlife predation, and traffic accidents. Although surgical castration is the most widely used method for controlling the male animal population, it is costly, time-consuming, and requires specialized professionals and post-operative care. Therefore, there is an urgent need for practical, low-cost, large-scale, and welfare-friendly non-surgical sterilization methods. This systematic review aimed to evaluate the efficacy of intratesticular or intraepididymal injections of sclerosing agents for inducing permanent chemical sterilization. A total of 38 peer-reviewed articles were retrieved from Medline/PubMed, Web of Science, Embase, and Scopus. Among sixteen substances, calcium chloride was the most frequently studied, followed by zinc gluconate, hypertonic saline, chlorhexidine gluconate, mannitol, and glycerol. A single bilateral intratesticular and intraepididymal injection damaged testicular and epididymal tissues, thereby disrupting spermatogenesis, steroidogenesis, and sperm transport. Despite differences in the methodology and outcomes among studies, most tested agents showed promising results in disrupting reproductive function. None of the compounds fully met the two key criteria for their practical use, including the absence of side effects and consistent induction of irreversible azoospermia or infertility. Nevertheless, calcium chloride and hypertonic saline emerged as the most promising candidates, due to their robust mechanistic profiles, broad evidence base, and favorable cost-effectiveness. Therefore, researchers may prioritize these two agents in future studies to develop standardized, safe, and field-applicable protocols for large-scale population control.
自由漫游的动物，特别是狗和猫的数量过剩，引起了重大的全球公共卫生问题，并导致了社会经济、生态、政治和伦理问题。这些动物自由繁殖，增加了人畜共患疾病传播、野生动物捕食和交通事故的风险。尽管手术阉割是控制雄性动物数量最广泛使用的方法，但它成本高，耗时长，需要专业的专业人员和术后护理。因此，迫切需要一种实用、低成本、规模化、福利友好的非手术绝育方法。本系统综述旨在评价睾丸内或附睾内注射硬化剂诱导永久性化学灭菌的疗效。共从Medline/PubMed、Web of Science、Embase和Scopus检索了38篇同行评议文章。在16种物质中，氯化钙是最常被研究的，其次是葡萄糖酸锌、高渗盐水、葡萄糖酸氯己定、甘露醇和甘油。单次双侧睾丸内和附睾内注射损伤睾丸和附睾组织，从而破坏精子发生、甾体发生和精子运输。尽管研究的方法和结果不同，但大多数测试的药物在破坏生殖功能方面显示出有希望的结果。没有一种化合物完全符合其实际使用的两个关键标准，包括没有副作用和持续诱导不可逆的无精子症或不孕症。然而，氯化钙和高渗盐水因其强大的机制特征、广泛的证据基础和良好的成本效益而成为最有希望的候选者。因此，研究人员可以在未来的研究中优先考虑这两种药物，以制定标准化、安全、现场适用的大规模种群控制方案。
{"title":"Non-surgical sterilization of male animals using sclerosing agents: A systematic review of intratesticular and intraepididymal injection protocols","authors":"Iara Magalhães Ribeiro , Renner Philipe Rodrigues Carvalho , Arabela Guedes de Azevedo Viana , Camilo Jose Ramirez-Lopez , Tayná Bolsam da Silva , Mariana Machado-Neves","doi":"10.1016/j.repbio.2025.101101","DOIUrl":"10.1016/j.repbio.2025.101101","url":null,"abstract":"<div><div>The overpopulation of free-roaming animals, particularly dogs and cats, poses a significant global public health concern, contributing to socioeconomic, ecological, political, and ethical issues. These animals reproduce freely, increasing the risk of zoonotic disease transmission, wildlife predation, and traffic accidents. Although surgical castration is the most widely used method for controlling the male animal population, it is costly, time-consuming, and requires specialized professionals and post-operative care. Therefore, there is an urgent need for practical, low-cost, large-scale, and welfare-friendly non-surgical sterilization methods. This systematic review aimed to evaluate the efficacy of intratesticular or intraepididymal injections of sclerosing agents for inducing permanent chemical sterilization. A total of 38 peer-reviewed articles were retrieved from Medline/PubMed, Web of Science, Embase, and Scopus. Among sixteen substances, calcium chloride was the most frequently studied, followed by zinc gluconate, hypertonic saline, chlorhexidine gluconate, mannitol, and glycerol. A single bilateral intratesticular and intraepididymal injection damaged testicular and epididymal tissues, thereby disrupting spermatogenesis, steroidogenesis, and sperm transport. Despite differences in the methodology and outcomes among studies, most tested agents showed promising results in disrupting reproductive function. None of the compounds fully met the two key criteria for their practical use, including the absence of side effects and consistent induction of irreversible azoospermia or infertility. Nevertheless, calcium chloride and hypertonic saline emerged as the most promising candidates, due to their robust mechanistic profiles, broad evidence base, and favorable cost-effectiveness. Therefore, researchers may prioritize these two agents in future studies to develop standardized, safe, and field-applicable protocols for large-scale population control.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"26 1","pages":"Article 101101"},"PeriodicalIF":2.5,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145508662","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}
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