Pub Date : 2025-12-01Epub Date: 2025-08-26DOI: 10.1016/j.repbio.2025.101059
Rabail Azhar Iqbal , Sophia Nazir
Gestational diabetes mellitus (GDM) is one of the commonly encountered medical disorders of pregnancy affecting women of childbearing age globally at an alarming rate and causing significant perinatal morbidity and adverse fetal outcomes. The intricate interchanges between genetic susceptibility, metabolic changes and environmental factors contribute to the altered β-cell function, insulin sensitivity and glucose metabolism leading to hyperglycaemia in pregnancy. However, the precise etiology of GDM remains incompletely understood. There is a compelling need for the identification of GDM in at-risk pregnant females at an early stage to improve maternal and fetal outcomes. Ongoing research has revealed numerous biomarkers that can be both predictive and diagnostic for GDM. This review aims to explore the various biomarkers that have increasing evidence for their use as predictors of GDM in the first and early second trimesters. The sensitivity, specificity, accuracy, and predictive power of these biomarkers have been compared to identify the ideal candidate(s), despite the effect of confounding factors. Throughout this review, research gaps were highlighted and future research directions were suggested to accurately diagnose GDM through a panel of efficacious biomarkers well before the disease manifests in later pregnancy.
{"title":"Potential novel biomarkers for gestational diabetes mellitus in first and early second trimesters: A comprehensive review","authors":"Rabail Azhar Iqbal , Sophia Nazir","doi":"10.1016/j.repbio.2025.101059","DOIUrl":"10.1016/j.repbio.2025.101059","url":null,"abstract":"<div><div>Gestational diabetes mellitus (GDM) is one of the commonly encountered medical disorders of pregnancy affecting women of childbearing age globally at an alarming rate and causing significant perinatal morbidity and adverse fetal outcomes. The intricate interchanges between genetic susceptibility, metabolic changes and environmental factors contribute to the altered β-cell function, insulin sensitivity and glucose metabolism leading to hyperglycaemia in pregnancy. However, the precise etiology of GDM remains incompletely understood. There is a compelling need for the identification of GDM in at-risk pregnant females at an early stage to improve maternal and fetal outcomes. Ongoing research has revealed numerous biomarkers that can be both predictive and diagnostic for GDM. This review aims to explore the various biomarkers that have increasing evidence for their use as predictors of GDM in the first and early second trimesters. The sensitivity, specificity, accuracy, and predictive power of these biomarkers have been compared to identify the ideal candidate(s), despite the effect of confounding factors. Throughout this review, research gaps were highlighted and future research directions were suggested to accurately diagnose GDM through a panel of efficacious biomarkers well before the disease manifests in later pregnancy.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 4","pages":"Article 101059"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144903738","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 : 2025-12-01Epub Date: 2025-09-04DOI: 10.1016/j.repbio.2025.101073
Yi Wang , Yuting Zhu , Yan Cui , Jiali Fang , Hong Zhong , Yujie Shi , Lan Liu , Xianwei Cui
Gestational diabetes mellitus (GDM) is a common and serious complication during pregnancy. Depleted next-generation probiotic, Akkermansia muciniphila (AKK) in GDM women indicates its potential on GDM prevention. However, the functions and mechanisms of AKK on GDM remain unclear. Due to the limited strategies for GDM therapy, combined with the anaerobic properties of AKK, herein, we reported pasteurized AKK functions as novel postbiotics which ameliorated glucose intolerance and insulin resistance in the GDM mouse model induced by high-fat diet (HFD) feeding combined with STZ. The oral administration of pasteurized AKK enhanced glucose homeostasis and alleviated placental inflammation in the GDM mouse model. Specifically, placental macrophage polarization was transferred by AKK treatment. In addition, the outer membrane protein of AKK, Amuc_1100, mimicked anti-inflammatory properties and improvement of GDM, which served as an effector protein. These findings demonstrate that oral AKK supplementation alleviated placental inflammatory responses through modulating macrophage polarization. Mechanically, we uncovered that a heat-stable outer membrane protein of AKK, Amuc_1100, mimics the anti-diabetic properties of pasteurized AKK through oral administration. Taken together, our findings demonstrated an effective treatment of GDM from the perspective of potential probiotic agents.
{"title":"Pasteurized Akkermansia muciniphila ameliorates insulin resistance by reducing placental inflammation in GDM mouse model","authors":"Yi Wang , Yuting Zhu , Yan Cui , Jiali Fang , Hong Zhong , Yujie Shi , Lan Liu , Xianwei Cui","doi":"10.1016/j.repbio.2025.101073","DOIUrl":"10.1016/j.repbio.2025.101073","url":null,"abstract":"<div><div>Gestational diabetes mellitus (GDM) is a common and serious complication during pregnancy. Depleted next-generation probiotic, Akkermansia muciniphila (AKK) in GDM women indicates its potential on GDM prevention. However, the functions and mechanisms of AKK on GDM remain unclear. Due to the limited strategies for GDM therapy, combined with the anaerobic properties of AKK, herein, we reported pasteurized AKK functions as novel postbiotics which ameliorated glucose intolerance and insulin resistance in the GDM mouse model induced by high-fat diet (HFD) feeding combined with STZ. The oral administration of pasteurized AKK enhanced glucose homeostasis and alleviated placental inflammation in the GDM mouse model. Specifically, placental macrophage polarization was transferred by AKK treatment. In addition, the outer membrane protein of AKK, Amuc_1100, mimicked anti-inflammatory properties and improvement of GDM, which served as an effector protein. These findings demonstrate that oral AKK supplementation alleviated placental inflammatory responses through modulating macrophage polarization. Mechanically, we uncovered that a heat-stable outer membrane protein of AKK, Amuc_1100, mimics the anti-diabetic properties of pasteurized AKK through oral administration. Taken together, our findings demonstrated an effective treatment of GDM from the perspective of potential probiotic agents.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 4","pages":"Article 101073"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144988998","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 : 2025-12-01Epub Date: 2025-09-27DOI: 10.1016/j.repbio.2025.101080
Kaixuan Wang , Haiwei He , Yadan Jin , Fangdi Zhang , Ruixue Ma , Fei Wang , Baohua Li , Guoliang Zhang
Soybean isoflavone (SI) was one type of phytoestrogen that competitively interacts with estrogen in the body, potentially interfering with endocrine balance, spermatogenesis, and the normal function of testicular cells. Nicotinamide mononucleotide (NMN), an important bioactive substance, enhances organ and tissue function through mechanisms such as reducing oxidative stress. However, limited information exists regarding the ability of NMN to improve phytoestrogen-induced damage to testis development in mice. The study investigated the protective effect of NMN on testicular damage in mice caused by SI. The results of this study revealed SI-treated mice exhibited a significant reduction in body weight, testicular index, and reproduction-related factors, as well as a marked increase in apoptosis. RNA sequencing (RNA-seq) results demonstrated that exposure to SI led to the enrichment of differentially expressed genes (DEGs) primarily in cellular autophagy and proliferation pathways within mouse testicular tissues. Administration of SI at doses of 200 mg/kg and 400 mg/kg downregulated the Rb1cc1 gene in the longevity-regulating pathway and the Vav2 gene in the cAMP signaling pathway in mouse testes. In contrast, treatment with 100 mg/kg NMN significantly alleviated the adverse effects induced by SI. In summary, NMN exhibited significant therapeutic potential in alleviating SI-induced testicular damage.
{"title":"Protective effect of nicotinamide mononucleotide against soybean isoflavone induced damage in mouse testis","authors":"Kaixuan Wang , Haiwei He , Yadan Jin , Fangdi Zhang , Ruixue Ma , Fei Wang , Baohua Li , Guoliang Zhang","doi":"10.1016/j.repbio.2025.101080","DOIUrl":"10.1016/j.repbio.2025.101080","url":null,"abstract":"<div><div>Soybean isoflavone (SI) was one type of phytoestrogen that competitively interacts with estrogen in the body, potentially interfering with endocrine balance, spermatogenesis, and the normal function of testicular cells. Nicotinamide mononucleotide (NMN), an important bioactive substance, enhances organ and tissue function through mechanisms such as reducing oxidative stress. However, limited information exists regarding the ability of NMN to improve phytoestrogen-induced damage to testis development in mice. The study investigated the protective effect of NMN on testicular damage in mice caused by SI. The results of this study revealed SI-treated mice exhibited a significant reduction in body weight, testicular index, and reproduction-related factors, as well as a marked increase in apoptosis. RNA sequencing (RNA-seq) results demonstrated that exposure to SI led to the enrichment of differentially expressed genes (DEGs) primarily in cellular autophagy and proliferation pathways within mouse testicular tissues. Administration of SI at doses of 200 mg/kg and 400 mg/kg downregulated the <em>Rb1cc1</em> gene in the longevity-regulating pathway and the <em>Vav2</em> gene in the cAMP signaling pathway in mouse testes. In contrast, treatment with 100 mg/kg NMN significantly alleviated the adverse effects induced by SI. In summary, NMN exhibited significant therapeutic potential in alleviating SI-induced testicular damage.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 4","pages":"Article 101080"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187923","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 : 2025-12-01Epub Date: 2025-09-26DOI: 10.1016/j.repbio.2025.101084
Syed Mohmad Shah , Manmohan Singh Chauhan
Bone Morphogenetic Proteins have been reported to play important roles in developmental biology across the species. The present study investigates the role of BMP4 in inducing germ lineage development. For this purpose, buffalo ES cells were subjected to in vitro differentiation under suspension as well as adherent cultures, at different BMP4 doses and time periods. ES cell colonies were differentiated as EBs as well as adherent monolayers under different BMP4 concentrations (20, 50 and 100 ngml−1) for different time intervals (4, 8 and 14 days). The differentiated cultures were subjected to transcriptional profiling for germ lineage associated genes. qPCR data analysis revealed that BMP4 at a concentration of 50–100 ngml−1 and for a period of 14 days led to maximum induction of such germ lineage associated genes like DAZL, VASA, PLZF (PGC-specific); SYCP3, MLH1, TNP1/2 and PRM2 (Meiotic genes); BOULE and TEKT1 (Spermatocyte markers); and GDF9, ZP2 and 3 (Oocyte markers). Immunocytochemical analysis of the differentiated cultures revealed positive expression of PGC-markers (c-KIT, DAZL and VASA), Meiotic-markers (SYCP3, MLH1 and PROTAMINE1), Spermatocyte-markers (ACROSIN and HAPRIN) and Oocyte-markers (GDF9 and ZP4), marking thereby the differentiation towards germ lineage cells. Oocyte-like structures (OLS) obtained in monolayer differentiated cultures harbored a big nucleus covered with a ZP4 coat, so typical of an oocyte. These OLS, in extended cultures, showed embryonic development and progressed through different embryonic-like structures. Global DNA methylation analysis of the optimally differentiated cultures showed significantly (p < 0.05) decreased levels of 5-methyl-2-deoxycytidine, a mimic of the methylation erasure process typical of gametogenesis. Expression of PGC markers, methylation erasure, and meiotic markers together with expression of spermatocyte and oocyte markers is suggestive of post-meiotic progression into spermatogenesis and oogenesis, respectively- thus reflecting onset of in vitro gametogenesis.
{"title":"Inducible differentiation of buffalo (Bubalus bubalis) embryonic stem cells towards male and female germ cell-like lineages under ex vivo BMP4-mediated stimulation","authors":"Syed Mohmad Shah , Manmohan Singh Chauhan","doi":"10.1016/j.repbio.2025.101084","DOIUrl":"10.1016/j.repbio.2025.101084","url":null,"abstract":"<div><div>Bone Morphogenetic Proteins have been reported to play important roles in developmental biology across the species. The present study investigates the role of BMP4 in inducing germ lineage development. For this purpose, buffalo ES cells were subjected to <em>in vitro</em> differentiation under suspension as well as adherent cultures, at different BMP4 doses and time periods. ES cell colonies were differentiated as EBs as well as adherent monolayers under different BMP4 concentrations (20, 50 and 100 ngml<sup>−1</sup>) for different time intervals (4, 8 and 14 days). The differentiated cultures were subjected to transcriptional profiling for germ lineage associated genes. qPCR data analysis revealed that BMP4 at a concentration of 50–100 ngml<sup>−1</sup> and for a period of 14 days led to maximum induction of such germ lineage associated genes like <em>DAZL</em>, <em>VASA</em>, <em>PLZF</em> (PGC-specific); <em>SYCP</em>3, <em>MLH</em>1, <em>TNP</em>1/2 and <em>PRM</em>2 (Meiotic genes); <em>BOULE</em> and <em>TEKT</em>1 (Spermatocyte markers); and <em>GDF</em>9, <em>ZP</em>2 and 3 (Oocyte markers). Immunocytochemical analysis of the differentiated cultures revealed positive expression of PGC-markers (c-KIT, DAZL and VASA), Meiotic-markers (SYCP3, MLH1 and PROTAMINE1), Spermatocyte-markers (ACROSIN and HAPRIN) and Oocyte-markers (GDF9 and ZP4), marking thereby the differentiation towards germ lineage cells. Oocyte-like structures (OLS) obtained in monolayer differentiated cultures harbored a big nucleus covered with a ZP4 coat, so typical of an oocyte. These OLS, in extended cultures, showed embryonic development and progressed through different embryonic-like structures. Global DNA methylation analysis of the optimally differentiated cultures showed significantly (p < 0.05) decreased levels of 5-methyl-2-deoxycytidine, a mimic of the methylation erasure process typical of gametogenesis. Expression of PGC markers, methylation erasure, and meiotic markers together with expression of spermatocyte and oocyte markers is suggestive of post-meiotic progression into spermatogenesis and oogenesis, respectively- thus reflecting onset of <em>in vitro</em> gametogenesis.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 4","pages":"Article 101084"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157715","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 : 2025-12-01Epub Date: 2025-10-11DOI: 10.1016/j.repbio.2025.101089
Shiyue Du , Yongfu Liu , Le Wang , Liuliu Shi , Xiaoying Zhao , Zhongcheng Yang , Wei Yuan , Xiaoying Deng , Jiahua Liu , Shenglei Feng , Rui Chen
Testicular tissue displays the most complex transcriptome across all tissues, with over 2000 genes exhibiting testis-enriched expression patterns. However, the functional ambiguity of such genes limits our understanding of spermatogenesis and male fertility. Here, we reanalyzed testicular gene expression profiles from patients with impaired spermatogenesis and identified that reduced expression of the testis-specific gene C3ORF22 was correlated with spermatogenic defects in humans. We showed that the murine ortholog BC048671 was predominant expressed in round spermatids, and its protein is present in spermatozoa. BC048671 knockout (KO) mice exhibited normal fertility, sperm morphology, and sperm motility. Intriguingly, RNA-Seq analysis revealed that BC048671 was the most markedly dysregulated gene in KO testes. Although proteomic analysis reveals the down-regulated ADAM family members (e.g., ADAM28 and ADAM2) in BC048671-null sperm, expression of the key downstream effector ADAM3 remained unaffected. These findings indicate that BC048671/C3ORF22 exhibits functional redundancy in spermatozoa. Although C3ORF22 is dispensable for male fertility, we consider it essential to report such negative results to guide researchers to prioritize efforts toward genes critical for human fertility.
{"title":"Testis-specific gene C3ORF22/BC048671 is dispensable for spermiogenesis and male fertility","authors":"Shiyue Du , Yongfu Liu , Le Wang , Liuliu Shi , Xiaoying Zhao , Zhongcheng Yang , Wei Yuan , Xiaoying Deng , Jiahua Liu , Shenglei Feng , Rui Chen","doi":"10.1016/j.repbio.2025.101089","DOIUrl":"10.1016/j.repbio.2025.101089","url":null,"abstract":"<div><div>Testicular tissue displays the most complex transcriptome across all tissues, with over 2000 genes exhibiting testis-enriched expression patterns. However, the functional ambiguity of such genes limits our understanding of spermatogenesis and male fertility. Here, we reanalyzed testicular gene expression profiles from patients with impaired spermatogenesis and identified that reduced expression of the testis-specific gene <em>C3ORF22</em> was correlated with spermatogenic defects in humans. We showed that the murine ortholog <em>BC048671</em> was predominant expressed in round spermatids, and its protein is present in spermatozoa. <em>BC048671</em> knockout (KO) mice exhibited normal fertility, sperm morphology, and sperm motility. Intriguingly, RNA-Seq analysis revealed that <em>BC048671</em> was the most markedly dysregulated gene in KO testes. Although proteomic analysis reveals the down-regulated ADAM family members (e.g., ADAM28 and ADAM2) in <em>BC048671</em>-null sperm, expression of the key downstream effector ADAM3 remained unaffected. These findings indicate that <em>BC048671</em>/<em>C3ORF22</em> exhibits functional redundancy in spermatozoa. Although <em>C3ORF22</em> is dispensable for male fertility, we consider it essential to report such negative results to guide researchers to prioritize efforts toward genes critical for human fertility.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 4","pages":"Article 101089"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145265529","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 : 2025-12-01Epub Date: 2025-09-09DOI: 10.1016/j.repbio.2025.101076
Yang Yang , Linfeng Li , Ning Zhang , Zheng Zhang , Zhengyang Wu , Dongmei Ji
Current research indicates that polyethylene terephthalate microplastics (PET-MPs) may significantly impair male reproductive function. This study aimed to investigate the potential molecular mechanisms underlying this impairment. Potential gene targets of PET-MPs were predicted via the SwissTargetPrediction database. GWAS summary statistics for male infertility were obtained from the GWAS Catalog, and eQTL data were acquired from the eQTLGen database. SMR analysis was subsequently performed to identify genes exhibiting significant causal associations with male infertility. The potential targets of PET-MPs contributing to male infertility were ultimately identified by intersecting the two gene sets. Additionally, bulk RNA-seq and scRNA-seq analyses were employed to elucidate the potential molecular mechanisms underlying PET-MPs-induced male infertility. Our findings suggest that CLK4 may serve as a functional target through which PET-MPs contribute to male infertility, with elevated CLK4 expression representing a significant risk factor. Molecular docking and molecular dynamics simulations demonstrated that PET-MPs can form stable binding conformations with the CLK4 protein. We further identified terminally differentiated CD4+ T cells as a prominent risk factor for male infertility, revealing a significant positive correlation between CLK4 expression levels and Th1 cell infiltration. Additionally, CLK4 exhibited a biphasic expression pattern during spermatocyte-to-sperm differentiation, initially increasing before subsequent downregulation. These observations indicate that PET-MPs may participate in the pathogenesis of male infertility by targeting CLK4 to modulate Th1 cell infiltration and disrupt normal spermatogenic processes. In conclusion, our study demonstrates that CLK4 may serve as a potential target for PET-MP-induced male infertility, and we further elucidate the underlying molecular mechanisms.
{"title":"Analyzing the toxicological effects of PET-MPs on male infertility: Insights from network toxicology, mendelian randomization, and transcriptomics","authors":"Yang Yang , Linfeng Li , Ning Zhang , Zheng Zhang , Zhengyang Wu , Dongmei Ji","doi":"10.1016/j.repbio.2025.101076","DOIUrl":"10.1016/j.repbio.2025.101076","url":null,"abstract":"<div><div>Current research indicates that polyethylene terephthalate microplastics (PET-MPs) may significantly impair male reproductive function. This study aimed to investigate the potential molecular mechanisms underlying this impairment. Potential gene targets of PET-MPs were predicted via the SwissTargetPrediction database. GWAS summary statistics for male infertility were obtained from the GWAS Catalog, and eQTL data were acquired from the eQTLGen database. SMR analysis was subsequently performed to identify genes exhibiting significant causal associations with male infertility. The potential targets of PET-MPs contributing to male infertility were ultimately identified by intersecting the two gene sets. Additionally, bulk RNA-seq and scRNA-seq analyses were employed to elucidate the potential molecular mechanisms underlying PET-MPs-induced male infertility. Our findings suggest that <em>CLK4</em> may serve as a functional target through which PET-MPs contribute to male infertility, with elevated <em>CLK4</em> expression representing a significant risk factor. Molecular docking and molecular dynamics simulations demonstrated that PET-MPs can form stable binding conformations with the <em>CLK4</em> protein. We further identified terminally differentiated CD4<sup>+</sup> T cells as a prominent risk factor for male infertility, revealing a significant positive correlation between <em>CLK4</em> expression levels and Th1 cell infiltration. Additionally, <em>CLK4</em> exhibited a biphasic expression pattern during spermatocyte-to-sperm differentiation, initially increasing before subsequent downregulation. These observations indicate that PET-MPs may participate in the pathogenesis of male infertility by targeting <em>CLK4</em> to modulate Th1 cell infiltration and disrupt normal spermatogenic processes. In conclusion, our study demonstrates that <em>CLK4</em> may serve as a potential target for PET-MP-induced male infertility, and we further elucidate the underlying molecular mechanisms.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 4","pages":"Article 101076"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019726","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 : 2025-12-01Epub Date: 2025-10-11DOI: 10.1016/j.repbio.2025.101088
Aya A. Mahmoud, Amel Ramadan Omar, Heba Ali Abd El-Rahman
Diabetes mellitus is a serious health issue that adversely affects male reproductive function and contributes to the rise in male infertility. This study examined the effectiveness of Casimiroa edulis leaf extract in improving reproductive impairment in diabetic male rats. Forty male rats were divided into control, Casimiroa edulis extract-treated, diabetic, and diabetic + Casimiroa edulis groups. Diabetic rats showed a notable reduction in sperm quality, a considerable rise in serum cholesterol levels, accompanied by a decrease in both androstenedione and testosterone levels. Histological examination of testicular tissue revealed degeneration of the seminiferous tubules, depletion of germinal cells, and lack of Leydig cells. They also exhibited a notable reduction in the activity of testicular enzymes, specifically 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase, along with a rise in the level of dehydroepiandrosterone. Casimiroa edulis treatment substantially reduced cholesterol levels, enhanced the activity of testicular enzymes, and restored testicle structure. Consequently, testosterone levels were elevated, and sperm quality was improved. To conclude, Casimiroa edulis may mitigate the negative effects of diabetes mellitus on the reproductive parameters of male rats and enhance fertility.
{"title":"Casimiroa edulis extract modulates testosterone levels, testicular enzymes and spermatogenesis disorders in streptozotocin-induced diabetic male rats","authors":"Aya A. Mahmoud, Amel Ramadan Omar, Heba Ali Abd El-Rahman","doi":"10.1016/j.repbio.2025.101088","DOIUrl":"10.1016/j.repbio.2025.101088","url":null,"abstract":"<div><div>Diabetes mellitus is a serious health issue that adversely affects male reproductive function and contributes to the rise in male infertility. This study examined the effectiveness of <em>Casimiroa edulis</em> leaf extract in improving reproductive impairment in diabetic male rats. Forty male rats were divided into control, <em>Casimiroa edulis</em> extract-treated, diabetic, and diabetic + <em>Casimiroa edulis</em> groups. Diabetic rats showed a notable reduction in sperm quality, a considerable rise in serum cholesterol levels, accompanied by a decrease in both androstenedione and testosterone levels. Histological examination of testicular tissue revealed degeneration of the seminiferous tubules, depletion of germinal cells, and lack of Leydig cells. They also exhibited a notable reduction in the activity of testicular enzymes, specifically 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase, along with a rise in the level of dehydroepiandrosterone. <em>Casimiroa edulis</em> treatment substantially reduced cholesterol levels, enhanced the activity of testicular enzymes, and restored testicle structure. Consequently, testosterone levels were elevated, and sperm quality was improved. To conclude, <em>Casimiroa edulis</em> may mitigate the negative effects of diabetes mellitus on the reproductive parameters of male rats and enhance fertility.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 4","pages":"Article 101088"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145265530","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}
Chlorpyrifos (CPS) is an organophosphate pesticide known to induce oxidative stress, apoptosis, and histopathological damage in male reproductive tissues. Ganoderma lucidum (GDL), a medicinal fungus rich in bioactive polysaccharides and triterpenoids, has demonstrated potent antioxidant and antiapoptotic properties in various models. This study aimed to evaluate the protective effects of GDL extract against CPS-induced testicular toxicity in male rats by assessing histological integrity, oxidative stress markers, apoptosis signaling, and hormonal balance. Twenty-four adult male Wistar rats were randomly divided into four groups (n = 6): Cont, CPS (20 mg/kg), GDL (150 mg/kg), and Treat. Treatments were administered orally once daily for 30 days. At the end of the study, the testes were harvested for morphometric and Cosentino histopathological scoring, immunohistochemistry for BAX, BCL2, and Ki67, RTqPCR quantification, biochemical assays of antioxidant enzymes and serum testosterone, LH, and FSH measurements. CPS treatment significantly elevated histopathological damage scores, and disrupted regular cell arrangement. IHC revealed increased BAX and decreased BCL2 and Ki67 expression, corroborated by the upregulation of Bax and Caspase3 transcripts and downregulation of Bcl2. Antioxidant enzymes were suppressed and MDA was elevated in the CPS group. Hormonal assays showed decreased testosterone and LH. Co-administration of GDL partially restored histological architecture, normalized Voronoi patterns, attenuated apoptotic marker alterations, enhanced antioxidant defenses, reduced lipid peroxidation, and recovered hormone levels toward control values. GDL extract confers significant protection against CPS-induced testicular injury by mitigating oxidative stress, modulating apoptotic pathways, and preserving endocrine function, highlighting its therapeutic potential against pesticide-related reproductive toxicity.
{"title":"Ganoderma lucidum mitigates oxidative stress and apoptosis in chlorpyrifos‑induced testicular toxicity in male rats","authors":"Afshin Talebinasab , Farrokh Modarresi , Ebrahim Salimi-Sabour , Mojtaba Sepandi , Maryam Ghorbani , Gholam Reza Kaka , Javad Raouf Sarshoori","doi":"10.1016/j.repbio.2025.101086","DOIUrl":"10.1016/j.repbio.2025.101086","url":null,"abstract":"<div><div>Chlorpyrifos (CPS) is an organophosphate pesticide known to induce oxidative stress, apoptosis, and histopathological damage in male reproductive tissues. <em>Ganoderma lucidum</em> (GDL), a medicinal fungus rich in bioactive polysaccharides and triterpenoids, has demonstrated potent antioxidant and antiapoptotic properties in various models. This study aimed to evaluate the protective effects of GDL extract against CPS-induced testicular toxicity in male rats by assessing histological integrity, oxidative stress markers, apoptosis signaling, and hormonal balance. Twenty-four adult male Wistar rats were randomly divided into four groups (n = 6): Cont, CPS (20 mg/kg), GDL (150 mg/kg), and Treat. Treatments were administered orally once daily for 30 days. At the end of the study, the testes were harvested for morphometric and Cosentino histopathological scoring, immunohistochemistry for BAX, BCL2, and Ki67, RTqPCR quantification, biochemical assays of antioxidant enzymes and serum testosterone, LH, and FSH measurements. CPS treatment significantly elevated histopathological damage scores, and disrupted regular cell arrangement. IHC revealed increased BAX and decreased BCL2 and Ki67 expression, corroborated by the upregulation of <em>Bax</em> and <em>Caspase3</em> transcripts and downregulation of <em>Bcl2</em>. Antioxidant enzymes were suppressed and MDA was elevated in the CPS group. Hormonal assays showed decreased testosterone and LH. Co-administration of GDL partially restored histological architecture, normalized Voronoi patterns, attenuated apoptotic marker alterations, enhanced antioxidant defenses, reduced lipid peroxidation, and recovered hormone levels toward control values. GDL extract confers significant protection against CPS-induced testicular injury by mitigating oxidative stress, modulating apoptotic pathways, and preserving endocrine function, highlighting its therapeutic potential against pesticide-related reproductive toxicity.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 4","pages":"Article 101086"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157714","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 : 2025-12-01Epub Date: 2025-09-27DOI: 10.1016/j.repbio.2025.101077
Sümeyye Çınar Özkan, Emine Toraman
In this study, the toxic effects of monosodium glutamate (MSG), a widely used food additive, on rat testicular tissue were evaluated and the potential protective role of tannic acid (TA), a natural polyphenolic compound, against this toxicity was investigated. For this purpose, 24 rats were divided into four groups (n=6). They were administered 2 g/kg monosodium glutamate (MSG) for 21 days. Subsequently, they were treated with 50 mg/kg tannic acid (TA). At the end of this period, testicular tissues were collected for molecular and biochemical analyses. Antioxidant enzyme activities (SOD, CAT, GPx, GST, GR), oxidative stress markers (GSH, MDA), inflammatory markers (TNF-α, iNOS, COX-2) and DNA damage indicator 8-OHdG (8-hydroxy-2′-deoxyguanosine) levels were analyzed in the experimental groups. In addition, expression levels of antioxidant defense (Sod, Cat, Gpx, Gst, Gr), inflammation (Tnf-α, Il-6, Nf-κB, Cox-2, Inos, Foxo1, Foxo3) and reproductive function-related genes (Dazl, Ddx4, Amh) were evaluated by qPCR. In the MSG group, a decrease in GSH level and a significant increase in MDA, TNF-α, iNOS and 8-OHdG levels were found (P<0.01). While a decrease was observed in SOD, CAT, GST and GR enzyme activities (P<0.01), no significant change was found in GPx activity. At the gene level, MSG administration suppressed the expression of genes related to antioxidant and germ cell functions and increased the expression of Tnf-α, lL-6, Cox-2 and Foxo3 (P<0.001). On the other hand, TA, both alone and in combination with MSG, demonstrated ameliorative effects on inflammation and oxidative stress, although not on all parameters. The data suggest that MSG induces oxidative stress, inflammation, DNA damage, and impaired germ cell function in testicular tissue. It was concluded that TA treatment suppresses these harmful effects, supports cellular defenses, and may help preserve testicular function.
{"title":"Tannic acid protection against oxidative and inflammatory effects of monosodium glutamate on testis: Molecular and biochemical approach","authors":"Sümeyye Çınar Özkan, Emine Toraman","doi":"10.1016/j.repbio.2025.101077","DOIUrl":"10.1016/j.repbio.2025.101077","url":null,"abstract":"<div><div>In this study, the toxic effects of monosodium glutamate (MSG), a widely used food additive, on rat testicular tissue were evaluated and the potential protective role of tannic acid (TA), a natural polyphenolic compound, against this toxicity was investigated. For this purpose, 24 rats were divided into four groups (n=6). They were administered 2 g/kg monosodium glutamate (MSG) for 21 days. Subsequently, they were treated with 50 mg/kg tannic acid (TA). At the end of this period, testicular tissues were collected for molecular and biochemical analyses. Antioxidant enzyme activities (SOD, CAT, GPx, GST, GR), oxidative stress markers (GSH, MDA), inflammatory markers (TNF-α, iNOS, COX-2) and DNA damage indicator 8-OHdG (8-hydroxy-2′-deoxyguanosine) levels were analyzed in the experimental groups. In addition, expression levels of antioxidant defense (<em>Sod, Cat, Gpx, Gst, Gr</em>), inflammation (<em>Tnf-α, Il-6, Nf-κB, Cox-2, Inos, Foxo1, Foxo3</em>) and reproductive function-related genes (<em>Dazl, Ddx4, Amh</em>) were evaluated by qPCR. In the MSG group, a decrease in GSH level and a significant increase in MDA, TNF-α, iNOS and 8-OHdG levels were found (P<0.01). While a decrease was observed in SOD, CAT, GST and GR enzyme activities (P<0.01), no significant change was found in GPx activity. At the gene level, MSG administration suppressed the expression of genes related to antioxidant and germ cell functions and increased the expression of <em>Tnf-α, lL-6, Cox-2</em> and <em>Foxo3</em> (P<0.001). On the other hand, TA, both alone and in combination with MSG, demonstrated ameliorative effects on inflammation and oxidative stress, although not on all parameters. The data suggest that MSG induces oxidative stress, inflammation, DNA damage, and impaired germ cell function in testicular tissue. It was concluded that TA treatment suppresses these harmful effects, supports cellular defenses, and may help preserve testicular function.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 4","pages":"Article 101077"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157840","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 : 2025-12-01Epub Date: 2025-08-27DOI: 10.1016/j.repbio.2025.101060
Daniyal Ezati , Reyhane Vardiyan , Ali Reza Talebi , Fatemeh Alipour , Hasan Pahang , Shabnam Mohammadi
Sperm cryopreservation is a conventional method to preserve sperm cells for a long time. This technique may cause various effects on sperm parameters. Therefore, applying beneficial antioxidants to decrease the adverse effects of freezing is noteworthy. Fisetin is a compound with antioxidant and anti-inflammatory properties. The main aim of the present study is to investigate the protective and beneficial effects of fisetin against cryo-damage on sperm functional parameters. In this experimental study, we analyzed 20 semen samples from asthenoteratozoospermic (AT) patients. Each sample was divided into three treatment groups: (1) fresh control (non-frozen), (2) cryopreservation medium (without fisetin), and (3) cryomedium supplemented with 50 μM fisetin. Freezing and thawing procedures were performed via the conventional method. Post-thaw analyses revealed that cryopreservation significantly reduced sperm motility, chromatin integrity, and mitochondrial membrane potential while increasing DNA fragmentation, malondialdehyde (MDA) levels, and apoptosis (p < 0.05). Fisetin supplementation markedly improved progressive motility (p < 0.05), reduced non-motile sperm percentage (p < 0.05), and decreased DNA fragmentation and MDA levels (p < 0.05). Additionally, it enhanced chromatin condensation and reduced apoptosis rates (p < 0.05). Fisetin attenuates cryo-damage through its antioxidant and anti-apoptotic properties, improving post-thaw sperm quality. Thus, incorporating fisetin into cryopreservation media could enhance sperm viability for assisted reproductive technologies (ART).
{"title":"Fisetin attenuates the adverse effects of freezing and thawing procedures on the biological characteristics of human asthenoteratozoospermia samples","authors":"Daniyal Ezati , Reyhane Vardiyan , Ali Reza Talebi , Fatemeh Alipour , Hasan Pahang , Shabnam Mohammadi","doi":"10.1016/j.repbio.2025.101060","DOIUrl":"10.1016/j.repbio.2025.101060","url":null,"abstract":"<div><div>Sperm cryopreservation is a conventional method to preserve sperm cells for a long time. This technique may cause various effects on sperm parameters. Therefore, applying beneficial antioxidants to decrease the adverse effects of freezing is noteworthy. Fisetin is a compound with antioxidant and anti-inflammatory properties. The main aim of the present study is to investigate the protective and beneficial effects of fisetin against cryo-damage on sperm functional parameters. In this experimental study, we analyzed 20 semen samples from asthenoteratozoospermic (AT) patients. Each sample was divided into three treatment groups: (1) fresh control (non-frozen), (2) cryopreservation medium (without fisetin), and (3) cryomedium supplemented with 50 μM fisetin. Freezing and thawing procedures were performed via the conventional method. Post-thaw analyses revealed that cryopreservation significantly reduced sperm motility, chromatin integrity, and mitochondrial membrane potential while increasing DNA fragmentation, malondialdehyde (MDA) levels, and apoptosis (p < 0.05). Fisetin supplementation markedly improved progressive motility (p < 0.05), reduced non-motile sperm percentage (p < 0.05), and decreased DNA fragmentation and MDA levels (p < 0.05). Additionally, it enhanced chromatin condensation and reduced apoptosis rates (p < 0.05). Fisetin attenuates cryo-damage through its antioxidant and anti-apoptotic properties, improving post-thaw sperm quality. Thus, incorporating fisetin into cryopreservation media could enhance sperm viability for assisted reproductive technologies (ART).</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 4","pages":"Article 101060"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144903737","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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