Spermatozoa contain a repertoire of RNAs considered to be potential functional fertility biomarkers.In this study,the gene expression of human sperm subpopulations with high(F1)and low(F2)motility from healthy normozo...Spermatozoa contain a repertoire of RNAs considered to be potential functional fertility biomarkers.In this study,the gene expression of human sperm subpopulations with high(F1)and low(F2)motility from healthy normozoospermic(N)and asthenozoospermic(A)individuals was evaluated using RNA microarray followed by functional genomic analysis of differentially expressed genes.Results from A-F1 versus N-F1,A-F2 versus N-F2,N-F1 versus N-F2,and A-F1 versus A-F2 comparisons showed a considerably larger set of downregulated genes in tests versus controls.Gene ontology(GO)analysis of A-F1 versus N-F1 identified 507 overrepresented biological processes(BPs),several of which are associated with sperm physiology.In addition,gene set enrichment analysis of the same contrast showed 110 BPs,36 cellular comp on ents,and 31 molecular functions,several of which are involved in sperm motility.A leadi ng・edge analysis of selected GO terms resulted in several down regulated genes encoding to dyn eins and kin esins,both related to sperm physiology.Furthermore,the predicted activation state of asthenozoospermia was increased,while fertility,cell movement of sperm,and gametogenesis were decreased.Interestingly,several downregulated genes characteristic of the canonical pathway protein ubiquitination were involved in asthenozoospermia activation.Conversely,GO analysis of A-F2 versus N-F2 did not identify overrepresented BPs,although the gene set enrichment analysis detected six enriched BPs,one cellular component,and two molecular functions.Overall,the results show differences in gene transcription between sperm subpopulations from asthenozoospermic and normozoospermic semen samples and allowed the identification of gene sets relevant to sperm physiology and reproduction.展开更多
The acrosome reaction （AR）, an absolute requirement for spermatozoa and egg fusion, requires the influx of Ca2＋ into the spermatozoa through voltage-dependent Ca2＋ channels and store-operated channels. Maitotoxin ...The acrosome reaction （AR）, an absolute requirement for spermatozoa and egg fusion, requires the influx of Ca2＋ into the spermatozoa through voltage-dependent Ca2＋ channels and store-operated channels. Maitotoxin （MTx）, a Ca2＋-mobilizing agent, has been shown to be a potent inducer of the mouse sperm AR, with a pharmacology similar to that of the zona pellucida （ZP）, possibly suggesting a common pathway for both inducers. Using recombinant human ZP3 （rhZP3）, mouse ZP and two MTx channel blockers （U73122 and U73343）, we investigated and compared the MTx- and ZP-induced ARs in human and mouse spermatozoa. Herein, we report that MTx induced AR and elevated intracellular Ca2＋ （[Ca2＋]~） in human spermatozoa, both of which were blocked by U73122 and U73343. These two compounds also inhibited the MTx-induced AR in mouse spermatozoa. In disagreement with our previous proposal, the AR triggered by rhZP3 or mouse ZP was not blocked by U73343, indicating that in human and mouse spermatozoa, the AR induction by the physiological ligands or by MTx occurred through distinct pathways. U73122, but not U73343 （inactive analogue）, can block phospholipase C （PLC）. Another PLC inhibitor, edelfosine, also blocked the rhZP3- and ZP-induced ARs. These findings confirmed the participation of a PLC-dependent signalling pathway in human and mouse zona protein-induced AR. Notably, edelfosine also inhibited the MTx-induced mouse sperm AR but not that of the human, suggesting that toxin-induced AR is PLC-dependent in mice and PLC-independent in humans.展开更多
炔诺酮（NET）可以通过抑制雌二醇（E2）对促性腺激素的正反馈作用达到阻止排卵。但有些研究结果表明合成孕激素抑制促性腺激素分泌的机制可能不同于天然孕酮。NET 能降低去势的完全型睾丸女性化病人促性腺激素水平的事实,提示 NET 在...炔诺酮（NET）可以通过抑制雌二醇（E2）对促性腺激素的正反馈作用达到阻止排卵。但有些研究结果表明合成孕激素抑制促性腺激素分泌的机制可能不同于天然孕酮。NET 能降低去势的完全型睾丸女性化病人促性腺激素水平的事实,提示 NET 在神经内分泌水平的作用机制可能间介于同细胞内非孕素、非雄素受体的互相作用。这些观察加上 NET 在啮齿类有雌素样作用等事实,促使作者观察了 NET展开更多
文摘Spermatozoa contain a repertoire of RNAs considered to be potential functional fertility biomarkers.In this study,the gene expression of human sperm subpopulations with high(F1)and low(F2)motility from healthy normozoospermic(N)and asthenozoospermic(A)individuals was evaluated using RNA microarray followed by functional genomic analysis of differentially expressed genes.Results from A-F1 versus N-F1,A-F2 versus N-F2,N-F1 versus N-F2,and A-F1 versus A-F2 comparisons showed a considerably larger set of downregulated genes in tests versus controls.Gene ontology(GO)analysis of A-F1 versus N-F1 identified 507 overrepresented biological processes(BPs),several of which are associated with sperm physiology.In addition,gene set enrichment analysis of the same contrast showed 110 BPs,36 cellular comp on ents,and 31 molecular functions,several of which are involved in sperm motility.A leadi ng・edge analysis of selected GO terms resulted in several down regulated genes encoding to dyn eins and kin esins,both related to sperm physiology.Furthermore,the predicted activation state of asthenozoospermia was increased,while fertility,cell movement of sperm,and gametogenesis were decreased.Interestingly,several downregulated genes characteristic of the canonical pathway protein ubiquitination were involved in asthenozoospermia activation.Conversely,GO analysis of A-F2 versus N-F2 did not identify overrepresented BPs,although the gene set enrichment analysis detected six enriched BPs,one cellular component,and two molecular functions.Overall,the results show differences in gene transcription between sperm subpopulations from asthenozoospermic and normozoospermic semen samples and allowed the identification of gene sets relevant to sperm physiology and reproduction.
文摘The acrosome reaction （AR）, an absolute requirement for spermatozoa and egg fusion, requires the influx of Ca2＋ into the spermatozoa through voltage-dependent Ca2＋ channels and store-operated channels. Maitotoxin （MTx）, a Ca2＋-mobilizing agent, has been shown to be a potent inducer of the mouse sperm AR, with a pharmacology similar to that of the zona pellucida （ZP）, possibly suggesting a common pathway for both inducers. Using recombinant human ZP3 （rhZP3）, mouse ZP and two MTx channel blockers （U73122 and U73343）, we investigated and compared the MTx- and ZP-induced ARs in human and mouse spermatozoa. Herein, we report that MTx induced AR and elevated intracellular Ca2＋ （[Ca2＋]~） in human spermatozoa, both of which were blocked by U73122 and U73343. These two compounds also inhibited the MTx-induced AR in mouse spermatozoa. In disagreement with our previous proposal, the AR triggered by rhZP3 or mouse ZP was not blocked by U73343, indicating that in human and mouse spermatozoa, the AR induction by the physiological ligands or by MTx occurred through distinct pathways. U73122, but not U73343 （inactive analogue）, can block phospholipase C （PLC）. Another PLC inhibitor, edelfosine, also blocked the rhZP3- and ZP-induced ARs. These findings confirmed the participation of a PLC-dependent signalling pathway in human and mouse zona protein-induced AR. Notably, edelfosine also inhibited the MTx-induced mouse sperm AR but not that of the human, suggesting that toxin-induced AR is PLC-dependent in mice and PLC-independent in humans.
文摘炔诺酮（NET）可以通过抑制雌二醇（E2）对促性腺激素的正反馈作用达到阻止排卵。但有些研究结果表明合成孕激素抑制促性腺激素分泌的机制可能不同于天然孕酮。NET 能降低去势的完全型睾丸女性化病人促性腺激素水平的事实,提示 NET 在神经内分泌水平的作用机制可能间介于同细胞内非孕素、非雄素受体的互相作用。这些观察加上 NET 在啮齿类有雌素样作用等事实,促使作者观察了 NET
