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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS · 2020 · IF 3.209

Determination of 27 amino acids’ levels in seminal plasma of asthenospermia and oligospermia patients and diagnostic value analysis

Mingjie Deng,Feiyan Lin,Caiping Zhou,Yuyan Chen,Leijie Xuan,Hongzhe Wang,Tiantian Feng,Lufeng Hu

Amino acids (AAs) are abundant in seminal fluid and play an important role in the reproduction process. However, the functional significance of AAs in seminal is not clear. This study was designed to profile the AAs in seminal fluid of asthenozoospermia (AS) and oligospermia (OL) patients and evaluate its potential diagnostic value. To determine the true function of AAs in seminal fluid, an ultra high performance liquid chromatography-mass spectrometry (UPLC-MS/MS) was developed and validated. The seminal fluid samples collected from 76 AS patients, 58 OL patients, and 76 healthy subjects were determined by UPLC-MS/MS and analyzed by fisher discriminant and receiver operating characteristic (ROC). The results showed that, the AAs levels were dramatically decreased in AS and OL patients compared with healthy subjects. What’s more there were significant variation in the AAs profile of AS and OL patients. Specifically, some polar AAs decreased, while nonpolar AAs increased in OL patients. Based on the level of AAs, 93.4 % of original and 90.9 % of cross-validated grouped cases were correctly classified between AS patients, OL patients, and healthy subjects. The further ROC analysis shows that glutamic acid, tyrosine, aspartic acid, proline, and tryptophan have the diagnostic value (P < 0.01) in the three groups. Moreover, aspartic acid and glutamic acid exhibit a high correlation (Correlation Coefficient >0.9) in AS, OL, and healthy subjects. In conclusion, there are significant variation in AAs profile in seminal plasma of AS and OL patients with high accuracy in fisher classification. The associations between the levels of AAs in seminal fluid of AS, OL, and healthy subjects may have clinical applications in providing valuable diagnostic indicator.

研究领域: 生殖医学 · 代谢组学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Oncotarget · 2017 · IF 5.168

Genistein up-regulates miR-20a to disrupt spermatogenesis via targeting Limk1

Hao Gu,Wei Wu,Beilei Yuan,Qiuqin Tang,Dan Guo,Yiqiu Chen,Yankai Xia,Lingqing Hu,Daozhen Chen,Jiahao Sha,Xinru Wang

Genistein (GEN) is one of the isoflavones that has effect on male reproduction. However, the underlying mechanism remains unknown. miRNAs are a type of small non-coding RNAs that play important roles in spermatogenesis. We measured the GEN levels and miR-17-92 cluster expression in infertile subjects and found that miR-17-92 might be involved in GEN induced abnormal spermatogenesis. To clarify, we fed adult ICR mice with different doses of GEN (0, 0.5, 5, 50 and 250 mg/kg/day) for 35 days to study the underlying mechanism. We found that sperm average path velocity, straight-line velocity and eurvilinear velocity of the mice orally with GEN at 5mg/kg/day were significantly decreased, the expression levels of miR-17 and miR-20a in mice testis were higher in corresponding group. We also found miR-20a was the only miRNA that differentially expressed both in human and mice. By applying bioinformatics methods, Limk1 was predicted to be the target gene of miR-20a that is involved in spermatogenesis. Limk1 were significantly decreased in the corresponding group. Dual-luciferase report assay also proved that miR-20a could directly target Limk1. These results implied that Limk1 might be the target gene of miR-20a that is involved in GEN induced abnormal spermatogenesis.

CAS / MDL: 8001-30-7
研究领域: 生殖生物学 · 分子生物学 · 基因组学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Veterinary Science · 2024 · IF 2.6

Effects of different ages on frozen semen quality and in vitro fertilization efficiency in Wannan black pigs

Xu Changzhi,Yang Xianshu,Sui Heming,Tong Xu,Zhang Dandan,Zheng Xianrui,Jiao Jun,Wang Chonglong,Cao Zubing,Zhang Yunhai

According to previous studies, the quality and fertilization rate of fresh sperm from boars of different ages were significantly different. However, the difference of freeze–thaw sperm quality and fertility in boars of different ages is unclear. In this study, boars of a Chinese native breed were assigned into two groups. Each group consisted of five boars aged aged either 2–3 years (young boars = YB) or 5–6 years (aging boars = AB) A total of 60 ejaculates for each group were collected and cryopreserved. Semen quality and in vitro fertility of post-thaw sperm was evaluated. The results showed that the concentration and motility of fresh sperm collected from AB were similar to YB, but their semen volume was higher than that in YB (p < 0.05). Frozen–thawed sperm of AB had lower viability than YB, and higher abnormal rate and reactive oxygen species (ROS) levels of YB (p < 0.05). There was no effect of the age on post-thaw sperm motility and time survival. Functional assessments indicated that increasing age markedly compromises the integrity of the sperm plasma membrane and acrosome, as well as mitochondrial functionality post-thaw, albeit without affecting DNA integrity. Furthermore, increasing age of boars reduces the ability of sperm to bind to the oocyte zona pellucida after thawing, delaying the time of the first embryo cleavage after fertilization. Finally, the early developmental efficiency of in vitro fertilized embryos progressing from 4-cell to blastocyst derived from post-thaw sperm in AB significantly decreased compared to those from YB (p < 0.05). Taken together, these results suggest that increasing age in boars impairs the quality and in vitro fertility of frozen thawed sperm.

研究领域: 动物科学 · 生殖生物学 · 兽医学
✓ 已验证 DOI PubMed 高影响因子
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FOOD AND CHEMICAL TOXICOLOGY · 2024 · IF 3.9

Protective effect of trehalose on sperm chromatin condensation failure and semen quality decline in BDE-209-exposed mice

Xin Gao,Huan He,Qi Zheng,Siju Chen,Yu Wei,Taifa Zhang,Yi Wang,Bo Wang,Dake Huang,Shengquan Zhang,Sumei Zhang,Jinxia Zhai

BDE-209 exposure induced male reproductive toxicity with sperm quality decline. However, the role of autophagy in this was unclear. The purpose was to evaluate the protective effect and its potential mechanism of trehalose (Tre, autophagy inducer) on reproductive damage during spermiogenesis induced by BDE-209. We used 2% w/v Tre and 75 mg/kg/d BDE-209 cotreated mice for 42 days. GC-2 spd cells were cotreated with Tre, chloroquine (CQ, inhibition of autophagic flux), compound C (CC, AMPK inhibitor), and BDE-209. Tre intake significantly recovered decrease in sexual organ ratio and poor sperm quality in BDE-209-exposed mice. Supplementation with Tre rescued sperm head malformation by improving aberrant histone-protamine exchange in BDE-209-exposed mice. However, Tre intake couldn't restore the acrosome biogenesis. In addition, Tre supplementation improved testicular damage induced by BDE-209. BDE-209 blocked autophagic flux with increased P62 and LC3BⅡ/Ⅰ levels. Mechanistically, CQ treatment aggravated elevation of P62 and LC3BⅡ/Ⅰ levels induced by BDE-209, otherwise, CC and Tre treatments inhibited the rise in p-AMPK, p-ULK1, P62 and LC3BⅡ/Ⅰ levels induced by BDE-209. Tre supplementation improved reproductive injury in BDE-209-exposed mice by regulating autophagic flow via AMPK-ULK1 signaling pathways, which providing a new theoretical basis and possible therapeutic targets for male reproductive toxicity.

CAS / MDL: 54-05-7 866405-64-3
研究领域: 生殖毒理学 · 分子生物学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF PROTEOME RESEARCH · 2022 · IF 5.37

Identification and Validation of Yak (Bos grunniens) Frozen–Thawed Sperm Proteins Associated with Capacitation and the Acrosome Reaction

Renzheng Zhang,Xian Guo,Chunnian Liang,Jie Pei,Pengjia Bao,Mancai Yin,Fude Wu,Min Chu,Ping Yan

To achieve fertilization, mammalian spermatozoa must undergo capacitation and the acrosome reaction (AR) within the female reproductive tract. However, the effects of cryopreservation on sperm maturation and fertilizing potential have yet to be established. To gain insight into changes in protein levels within sperm cells prepared for use in the context of fertilization, a comprehensive quantitative proteomic profiling approach was used to analyze frozen–thawed Ashidan yak spermatozoa under three sequential conditions: density gradient centrifugation-based purification, incubation in a capacitation medium, and treatment with the calcium ionophore A23187 to facilitate AR induction. In total, 3280 proteins were detected in these yak sperm samples, of which 3074 were quantified, with 68 and 32 being significantly altered following sperm capacitation and AR induction. Differentially abundant capacitation-related proteins were enriched in the metabolism and PPAR signaling pathways, while differentially abundant AR-related proteins were enriched in the AMPK signaling pathway. These data confirmed a role for superoxide dismutase 1 (SOD1) as a regulator of sperm capacitation while also offering indirect evidence that heat shock protein 90 alpha (HSP90AA1) regulates the AR. Together, these findings offer a means whereby sperm fertility-related marker proteins can be effectively identified. Data are available via Proteome Xchange with identifier PXD035038.

CAS / MDL: 41931-13-9
研究领域: 生殖生物学 · 蛋白质组学 · 动物科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MOLECULAR THERAPY · 2025 · IF 12

METTL5 deficiency induces oligoasthenoteratozoospermia via impaired 18S rRNA m6A methylation in humans and mice

Mengya Zhang,Xueguang Zhang,Chen Tan,Ting Jiang,Zheng Cao,Yufei Chen,Feng Qiao,Gelin Huang,Chaoye Ma,Huixia Li,Mei Ye,Lei Wang,Liandong Zuo,Jun Yu,Xiaofeng Li,Yunfang Zhang,Yue-Qiu Tan,Shuibin Lin,Wenming Xu,Hao Chen

Recent studies have highlighted RNA modifications as integral regulators of gene expression during spermatogenesis. Ribosomal RNAs (rRNAs) are the most abundant RNA in cells, while the function and clinical relevance of rRNA modifications in spermatogenesis remain poorly understood. Here, we identified 4 pathogenic heterozygous variants of METTL5 in 1,427 patients with male infertility characterized as oligoasthenoteratozoospermia (OAT). The pathogenic variants of METTL5 led to the significantly decreased expression level of METTL5. Null mutation of 18S rRNA methyltransferase Mettl5 led to male infertility attributed to OAT during spermiogenesis, presenting defects in both the sperm head and tail. Notwithstanding the absence of notable changes in global translation after Mettl5 loss, we observed a compromised translational efficiency of mRNAs encoding proteins crucial for spermiogenesis, including Gk2 , Akap4 , Fsip2 , Odf2 , and Pgk2 . Intriguingly, therapeutic interventions via intracytoplasmic sperm injection in OAT couples with these variants resulted in successful pregnancies. These insights not only identify METTL5-mediated 18S rRNA m 6 A modification as a novel genetic determinant for OAT but also offer a new target to the genetic counseling, clinical diagnosis, and potential treatment strategies for male infertility.

CAS / MDL: 1330-20-7 64-17-5
研究领域: 分子生物学 · 遗传学 · 生殖医学 · RNA修饰 · 发育生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Food & Function · 2024 · IF 5.1

Flaxseed oil attenuates PFOS-induced testicular damage by regulating RNA alternative splicing

Jingyi Ren,Jiarui Liu,Jinshi Zuo,Zhenao Zhang,Dan Huang,Xuanyi Liu,Miaomiao Lu,Yadong Zhang,Yang Su,Yuxia Ma

Background: Perfluorooctane sulfonate (PFOS) is a persistent, widely present environmental pollutant, and its toxicity to male reproduction has gradually attracted attention. Flaxseed oil (FO) is a dietary oil abundant in α-linolenic acid and has been demonstrated to possess multiple health benefits. However, whether FO protects against PFOS-induced testicular injury and its mechanism remain unclear. Methods: C57/BL6 mice were gavaged with different concentrations of FO or PFOS (10 mg kg−1) for 28 days. Blood and testicular tissues were collected for histopathology, proteomics, and biochemical and molecular analyses. Results: Our results showed that FO supplementation significantly attenuated PFOS-induced testicular injury, as indicated by histopathological changes, decreased oxidative stress level, increased sperm count, decreased rate of sperm malformation, and improved functional markers of spermatogenesis. Proteomic analysis showed that differentially expressed proteins were notably enriched in spliceosome pathways. Machine learning algorithms were used to screen the hub gene, and PRPF3 and PUF60 proteins were found to be important for FO to exert protective benefits to testicular injury. Western blot results confirmed that FO supplementation could increase the protein expression of PRPF3 and decrease the protein expression of PUF60 in PFOS-exposed mice. Conclusions: This study revealed that FO can alleviate PFOS-induced testicular dysfunction by regulating RNA alternative splicing. The spliceosome-related proteins PRPF3 and PUF60 may be the potential targets for FO to alleviate PFOS-induced testicular injury. FO supplementation may be an effective dietary intervention to prevent adverse effects of PFOS on testes.

CAS / MDL: 8001-22-7
研究领域: 毒理学 · 生殖生物学 · 营养科学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Human Reproduction Open · 2025 · IF 11.1

Hypoxia exposure impairs male fertility via inhibiting Septin2-mediated spermatogonial proliferation

Li Zhibin,Li Shuying,Xiao Yufeng,Guo Junfeng,Zhou Jianchun,Chen Yang,Yang Juan,Gong Chunli,He Bing,Wu Yuyun,Gao Nannan,Yang Huan,Gao Limin,Hu Hua,Zhang Yunfang,Yang Shiming

What are the molecular mechanisms underlying hypoxia-induced male reproductive impairment?Hypoxia compromises Septin2 (Sept2) transcription in spermatogonia, which impedes spermatogonial proliferation through protein phosphatase 2A (PP2A)-dependent AKT dephosphorylation.Hypoxia is associated with impaired spermatogenesis and poor sperm parameters in men. Spermatogonia proliferation, a crucial early step in spermatogenesis, is essential for maintaining the spermatogenic cell population and ensuring sperm quality. However, the connection between hypoxia and spermatogonial proliferation remains poorly understood, and treatment options for hypoxia-related reproductive disorders are limited.A cross-sectional study analyzed semen samples from 24 high-altitude (HA) residents, 6 pathological hypoxia (PH) patients, and 19 healthy controls to evaluate hypoxia-associated sperm parameter alterations. Complementary animal studies employing a hypobaric chamber-induced hypoxic mouse model (n = 5) confirmed reproductive impairments through assessment of birth rates, sperm quality, and testicular histopathology. Transcriptomic profiling of hypoxic versus normoxic mouse testes (n = 3/group) identified spermatogonial proliferation defects as a predominant pathological feature and pinpointed Sept2 as a candidate mediator. Subsequent mechanistic investigations employed in vitro hypoxic culture of spermatogonial cell lines under hypoxic conditions coupled with pharmacological modulation of PP2A activity in mice (n = 3-5 per intervention group) to delineate the underlying molecular pathways.Semen parameters were evaluated using computer-assisted sperm analysis (CASA; for sperm concentration, count, and motility), morphological staining (Pap staining for sperm deformity), and eosin-nigrosin staining (for sperm viability). In hypoxic mouse model, fertility outcomes were assessed through fertility assessment (mating experiments), sperm parameters (CASA), testicular histology (H&E staining), and spermatogonia proliferation (immunohistochemistry and qPCR). In hypoxic spermatogonial cell models, cell proliferation was detected using CCK-8, EdU incorporation, flow cytometry, and western blotting. Sept2 manipulation (knockdown/overexpression), followed by mechanistic analyses (dual-luciferase reporter assay, DNA pulldown/mass spectrometry, TMT-based quantitative proteomics, co-immunoprecipitation, etc), was performed to investigate the mechanism underlying hypoxia-regulated spermatogonia proliferation. The SEPT2 inhibitor forchlorfenuron (FCF), the PP2A agonists celastrol, erlotinib, and FTY720, as well as PP2A inhibitor okadaic acid (OA) were used to investigate the role of the SEPT2-PP2A-AKT axis in male fertility regulation.Both human populations (HA residents and PH patients) and mouse model consistently demonstrated hypoxia-related reproductive dysfunction. Mechanistic analyses revealed that hypoxia significantly downregulated Sept2 expression in spermatogonia, concomitant with impaired proliferative capacity. Sept2 knockdown in normoxic mice the hypoxia-induced defects in spermatogenesis. Complementary in vitro studies confirmed that Sept2 depletion impaired spermatogonial proliferation by inducing G1-S phase arrest, while its overexpression mitigated hypoxia-related proliferative defects. Further investigation revealed that hypoxia disrupts Sept2 transcription by interfering with the binding of RNA polymerase II subunit A (POLR2A) to the Sept2 promoter. The consequent reduction in Sept2 expression led to stabilization of the B56γ regulatory subunit of PP2A, resulting in enhanced AKT dephosphorylation and subsequent suppressed proliferation. Pharmacological intervention with the PP2A inhibitor OA restored reproductive competence and sperm quality in hypoxic mice, whereas PP2A agonists exacerbated these deficits.RNA-seq data are deposited in China National Center for Bioinformation (CNCB) under accession number PRJCA035733.This study focused on the effects of hypoxia on sperm parameters. Additional factors such as alterations in reproductive hormones and sexual function may contribute to hypoxia-induced infertility and warrant further research.This study identifies the SEPT2-PP2A/B56γ-AKT axis as a key regulator in hypoxia-related spermatogonia proliferation impairment. PP2A inhibitors such as OA may offer a therapeutic strategy to protect male fertility under hypoxic conditions.This work was supported by the National Natural Science Foundation of China (No. 82101688) and Natural Science Foundation of Chongqing (No. CSTB2022NSCQ-MSX0943). The authors have no conflicts of interest to declare.

CAS / MDL: 133407-82-6 68157-60-8
研究领域: 生殖生物学 · 分子生物学 · 医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Toxins · 2024 ·Vol. 16 ·期 3 ·121 · IF 3.9

Alleviative Effect of Rutin on Zearalenone-Induced Reproductive Toxicity in Male Mice by Preventing Spermatogenic Cell Apoptosis and Modulating Gene Expression in the Hypothalamic–Pituitary–Gonadal Axis

Hira Sayed,Qiongqiong Zhang,Yu Tang,Yanan Wang,Yongpeng Guo,Jianyun Zhang,Cheng Ji,Qiugang Ma,Lihong Zhao

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin found in many agricultural products and can cause reproductive disorders, mainly affecting spermatogenesis in male animals. Rutin (RUT) is a natural flavonoid compound recognized for its significant antioxidant, anti-inflammatory and estrogenic properties. The present study aimed to determine the protective role of RUT against ZEN-induced reproductive toxicity in male mice. Twenty-four adult Kunming male mice were divided into four groups: control, RUT (500 mg/kg RUT), ZEN (10 mg/kg ZEN), ZEN + RUT (500 mg/kg RUT + 10 mg/kg ZEN), with six replicates per treatment. The results indicated that RUT mitigated ZEN-induced disruption in spermatogenic cell arrangement, decreased spermatozoa count, and increased sperm mortality in the testes. RUT significantly restored ZEN-induced reduction in T, FSH, LH, and E2 serum levels. Moreover, RUT mitigated ZEN-induced apoptosis by increasing the mRNA expression level ofbcl-2, decreasing the mRNA expression level ofkiss1-r, and decreasing the protein expression level of caspase 8 in reproductive tissues. These findings indicate the protective role of RUT against ZEN-induced reproductive toxicity in male mice by regulating gonadotropin and testosterone secretions to maintain normal spermatogenesis via the HPG axis, which may provide a new application direction for RUT as a therapeutic agent to mitigate ZEN-induced reproductive toxicity.

研究领域: 毒理学 · 生殖生物学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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SENSORS AND ACTUATORS B-CHEMICAL · 2023 · IF 8.4

Revelation of β-galactosidase variation in senile sperms and organs via a silicon xanthene near-infrared probe

Yi-Min Shan,Li-Na Zhang,Si-Xian Wu,Xiao-Liang Li,Hong Zhang,Fei-Fan Xiang,Fan-Yuan Yu,Yan-Hong Liu,Xiao-Qi Yu,Kun Li,Wen-Ming Xu,Kang-Kang Yu

β -galactosidase has become the most widely used bio-marker in cellular senescence, however, it is unknown whether there are same changes in β -galactosidase activity during sperm senescence. Understanding the changes in such indicator during sperm senescence is important for sperm sorting and in vitro fertilization. Herein, we developed a NIR probe Si-βGal-P by using silicon xanthene as fluorophore . Si-βGal-P showed a good affinity to β -galactosidase together with high specificity and strong anti-interference ability. And Si-βGal-P was proved to be able to assess β -galactosidase in three different replicate senescence models. Besides, Si-βGal-P could easily pass blood-brain barrier and successfully imaged the up-regulated β -galactosidase activity in 34-week-old mouse brain. In addition, Si-βGal-P was successfully applied to hydrogen peroxide-induced premature sperm and visualized the up-regulated β -galactosidase activity for the first time, providing sperm senescence with a valid labeling tool.

研究领域: 细胞衰老 · 生殖生物学 · 分子成像
✓ 已验证 DOI 高影响因子
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HUMAN REPRODUCTION · 2024 · IF 6

Both protein and non-protein components in extracellular vesicles of human seminal plasma improve human sperm function via CatSper-mediated calcium signaling

Zhang Xiaoning,Liang Min,Song Dandan,Huang Rongzu,Chen Chen,Liu Xiaojun,Chen Houyang,Wang Qingxin,Sun Xiaoli,Song Jian,Zhang Jiali,Kang Hang,Zeng Xuhui

STUDY QUESTIONWhat is the significance and mechanism of human seminal plasma extracellular vesicles (EVs) in regulating human sperm functions?SUMMARY ANSWEREV increases the intracellular Ca2+ concentrations [Ca2+]i via extracellular Ca2+ influx by activating CatSper channels, and subsequently modulate human sperm motility, especially hyperactivated motility, which is attributed to both protein and non-protein components in EV.WHAT IS KNOWN ALREADYEVs are functional regulators of human sperm function, and EV cargoes from normal and asthenozoospermic seminal plasma are different. Pre-fusion of EV with sperm in the acidic and non-physiological sucrose buffer solution could elevate [Ca2+]i in human sperm. CatSper, a principle Ca2+ channel in human sperm, is responsible for the [Ca2+]i regulation when sperm respond to diverse extracellular stimuli. However, the role of CatSper in EV-evoked calcium signaling and its potential physiological significance remain unclear.STUDY DESIGN, SIZE, DURATIONEV isolated from the seminal plasma of normal and asthenozoospermic semen were utilized to investigate the mechanism by which EV regulates calcium signal in human sperm, including the involvement of CatSper and the responsible cargoes in EV. In addition, the clinical application potential of EV and EV protein-derived peptides were also evaluated. This is a laboratory study that went on for more than 5 years and involved more than 200 separate experiments.PARTICIPANTS/MATERIALS, SETTING, METHODSSemen donors were recruited in accordance with the Institutional Ethics Committee on human subjects of the Affiliated Hospital of Nantong University and Jiangxi Maternal and Child Health Hospital. The Flow NanoAnalyzer, western blotting, and transmission electron microscope were used to systematically characterize seminal plasma EV. Sperm [Ca2+]i responses were examined by fluorimetric measurement. The whole-cell patch-clamp technique was performed to record CatSper currents. Sperm motility parameters were assessed by computer-assisted sperm analysis. Sperm hyperactivation was also evaluated by examining their penetration ability in viscous methylcellulose media. Protein and non-protein components in EV were analyzed by liquid chromatography-mass spectrum. The levels of prostaglandins, reactive oxygen species, malonaldehyde, and DNA integrity were detected by commercial kits.MAIN RESULTS AND THE ROLE OF CHANCEEV increased [Ca2+]i via an extracellular Ca2+ influx, which could be suppressed by a CatSper inhibitor. Also, EV potentiated CatSper currents in human sperm. Furthermore, the EV-in [Ca2+]i increase and CatSper currents were absent in a CatSper-deficient sperm, confirming the crucial role of CatSper in EV induced Ca2+ signaling in human sperm. Both proteins and non-protein components of EV contributed to the increase of [Ca2+]i, which were important for the effects of EV on human sperm. Consequently, EV and its cargos promoted sperm hyperactivated motility. In addition, seminal plasma EV protein-derived peptides, such as NAT1-derived peptide (N-P) and THBS-1-derived peptide (T-P), could activate the sperm calcium signal and enhance sperm function. Interestingly, EV derived from asthenozoospermic semen caused a lower increase of [Ca2+]i than that isolated from normal seminal plasma (N-EV), and N-EV significantly improved sperm motility and function in both asthenozoospermic samples and frozen-thawed sperm.LARGE SCALE DATAN/A.LIMITATIONS, REASONS FOR CAUTIONThis was an in vitro study and caution must be taken when extrapolating the physiological relevance to in vivo regulation of sperm.WIDER IMPLICATIONS OF THE FINDINGSOur findings demonstrate that the CatSper-mediated-Ca2+ signaling is involved in EV-modulated sperm function under near physiological conditions, and EV and their derivates are a novel CatSper and sperm function regulators with potential for clinical application. They may be developed to improve sperm motility resulting from low [Ca2+]i response and/or freezing and thawing.STUDY FUNDING/COMPETING INTEREST(S)This research was supported by the National Natural Science Foundation of China (32271167), the Social Development Project of Jiangsu Province (BE2022765), the Nantong Social and People's Livelihood Science and Technology Plan (MS22022087), the Basic Science Research Program of Nantong (JC22022086), and the Jiangsu Innovation and Entrepreneurship Talent Plan (JSSCRC2021543). The authors declare no conflict of interest.

CAS / MDL: 745-65-3
研究领域: 生殖生物学 · 细胞生物学 · 分子生物学 · 生理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ANDROLOGIA · 2014 ·Vol. 47 ·期 9 ·995-1003 · IF 1.172

Strontium fructose 1, 6-diphosphate alleviate cyclophosphamide-induced oligozoospermia by improving antioxidant and inhibiting testicular apoptosis via FAS/FASL pathway

J. Li,Y. Hu,Q. Zhang,B. Ma,Z. Wu,Y. Wang,J. Sun,J. Zhu,H. Ying,P. Ouyang

Summary This study investigated the treatment effects of a new compound, strontium fructose 1, 6-diphosphate (FDP-Sr), in cyclophosphamide (CP)-induced oligozoospermia. FDP-Sr, with extra high-energy supply, could reverse male hypogonadism in the testis. Male Wistar rats were randomly divided into three groups: control group (vehicle treated), CP group and CP + FDP-Sr group. Both CP group and CP + FDP-Sr groups were orally administered CP (20 mg kg −1 ) consecutively for the first 7 days to establish CP-induced testicular toxic models. Subsequently, CP group was given orally distilled water per day, whereas CP + FDP-Sr group was received FDP-Sr (200 mg kg −1 ) for 49 days. Compared to the CP group, the FDP-Sr group showed significantly increased levels of serum testosterone, testis relative weights and epididymal sperm counts in rats. In addition, rats treated by FDP-Sr showed the recuperative activities of testicular marker enzymes and normalised levels of antioxidants in tissue. Testicular protection of FDP-Sr was further demonstrated by enhancing expression of P450scc, reducing ability of FAS/FASL and generating cytoprotection in the histopathological study. FDP-Sr appeared to possess an ability to attenuate CP-induced reproduction toxicity via the activation of antioxidants and steroidogenesis enzymes, and alleviate oligozoospermia via inhibition of testicular apoptosis by FAS/FASL pathway.

CAS / MDL: 50-18-0
研究领域: 药理学 · 生殖生物学 · 毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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