Dear Editor,In a recent study,we isolated a protein from human oviductal secretion that could bind to spermatozoa[1].This protein was identified through chromatography and tandem mass spectrometry as human S100A9 and ...Dear Editor,In a recent study,we isolated a protein from human oviductal secretion that could bind to spermatozoa[1].This protein was identified through chromatography and tandem mass spectrometry as human S100A9 and was detected in human tubal epithelium and oviductal secretions.S100A9 belongs to the S100 protein family[2],which has been found in various body fluids and tissues,and plays a role in extracellular functions,such as the enhancement of neutrophil extravasation,induction of proinflammatory cytokine release,antimicrobial properties through divalent ion sequestration,and modulation of cellular proliferation,differentiation,and apoptosis,as well as acting as a chemotactic factor[3–4].Because S100A9 is involved in various pathologies and the physiology of inflammation,research on S100A9 effects continues to grow rapidly.Recently,we have shown the presence of binding sites for S100A9 on human spermatozoa,and also found that S100A9 modulated certain sperm capacitation parameters in vitro,such as the induced acrosome reaction(AR)[1].To continue our studies on sperm function parameters,the current study aimed to express and purify human recombinant S100A9 and to assess its effect on sperm capacitation parameters,specifically the AR.展开更多
In renewing tissues,mutations conferring selective advantage may result in clonal expansions1-4.In contrast to somatic tissues,mutations driving clonal expansions in spermatogonia(CES)are also transmitted to the next ...In renewing tissues,mutations conferring selective advantage may result in clonal expansions1-4.In contrast to somatic tissues,mutations driving clonal expansions in spermatogonia(CES)are also transmitted to the next generation.This results in an effective increase of de novo mutation rate for CES drivers5-8.CES was originally discovered through extreme recurrence of de novo mutations causing Apert syndrome5.Here,we develop a systematic approach to discover CES drivers as hotspots of human de novo mutation.Our analysis of 54,715 trios ascertained for rare conditions9-13,6,065 control trios12,14-19 and population variation from 807,162 mostly healthy individuals20 identifies genes manifesting rates of de novo mutations inconsistent with plausible models of disease ascertainment.We propose 23 genes hypermutable at loss-of-function(LoF)sites as candidate CES drivers.An extra 17 genes feature hypermutable missense mutations at individual positions,suggesting CES acting through gain of function.CES increases the average mutation rate roughly 17-fold for LoF genes in both control trios and sperm and roughly 500-fold for pooled gain-of-function sites in sperm21.Positive selection in the male germline elevates the prevalence of genetic disorders and increases polymorphism levels,masking the effect of negative selection in human populations.展开更多
Meiotic resumption in mammalian oocytes involves nuclear and organelle structural changes,notably the chromatin configuration transition from a non-surrounding nucleolus(NSN)to surrounding nucleolus(SN)in germinal ves...Meiotic resumption in mammalian oocytes involves nuclear and organelle structural changes,notably the chromatin configuration transition from a non-surrounding nucleolus(NSN)to surrounding nucleolus(SN)in germinal vesicle oocytes.In the current study,we found that nuclear speckles(NSs),a subnuclear structure mainly composed of serine-arginine(SR)proteins,changed from a diffuse spotted distribution in mouse NSN oocytes to an aggregated pattern in SN oocytes.We also found that the SR protein-specific kinase 1(SRPK1),an enzyme that phosphorylates SR proteins,co-localized with NSs at the SN stage,and that NSN oocytes failed to transition to SN oocytes after the inhibition of SRPK1 activity.Furthermore,the typical structure of the chromatin ring around the nucleolus in SN oocytes collapsed after treatment with an SRPK1 inhibitor.Mechanistically,phosphorylated SR proteins were found to be related to chromatin as shown by a salt extraction experiment,and in situ DNaseⅠassay showed that the accessibility of chromatin was enhanced in SN oocytes when SRPK1 was inhibited,accompanied by a decreased repressive modification on histone and the abnormal recurrence of a transcriptional signal.In conclusion,our results indicated that SRPK1-regulated phosphorylation of SR proteins was involved in the NSN-SN transition and played an important role in maintaining the condensed nucleus of SN oocytes via interacting with chromatin.展开更多
文摘Dear Editor,In a recent study,we isolated a protein from human oviductal secretion that could bind to spermatozoa[1].This protein was identified through chromatography and tandem mass spectrometry as human S100A9 and was detected in human tubal epithelium and oviductal secretions.S100A9 belongs to the S100 protein family[2],which has been found in various body fluids and tissues,and plays a role in extracellular functions,such as the enhancement of neutrophil extravasation,induction of proinflammatory cytokine release,antimicrobial properties through divalent ion sequestration,and modulation of cellular proliferation,differentiation,and apoptosis,as well as acting as a chemotactic factor[3–4].Because S100A9 is involved in various pathologies and the physiology of inflammation,research on S100A9 effects continues to grow rapidly.Recently,we have shown the presence of binding sites for S100A9 on human spermatozoa,and also found that S100A9 modulated certain sperm capacitation parameters in vitro,such as the induced acrosome reaction(AR)[1].To continue our studies on sperm function parameters,the current study aimed to express and purify human recombinant S100A9 and to assess its effect on sperm capacitation parameters,specifically the AR.
文摘In renewing tissues,mutations conferring selective advantage may result in clonal expansions1-4.In contrast to somatic tissues,mutations driving clonal expansions in spermatogonia(CES)are also transmitted to the next generation.This results in an effective increase of de novo mutation rate for CES drivers5-8.CES was originally discovered through extreme recurrence of de novo mutations causing Apert syndrome5.Here,we develop a systematic approach to discover CES drivers as hotspots of human de novo mutation.Our analysis of 54,715 trios ascertained for rare conditions9-13,6,065 control trios12,14-19 and population variation from 807,162 mostly healthy individuals20 identifies genes manifesting rates of de novo mutations inconsistent with plausible models of disease ascertainment.We propose 23 genes hypermutable at loss-of-function(LoF)sites as candidate CES drivers.An extra 17 genes feature hypermutable missense mutations at individual positions,suggesting CES acting through gain of function.CES increases the average mutation rate roughly 17-fold for LoF genes in both control trios and sperm and roughly 500-fold for pooled gain-of-function sites in sperm21.Positive selection in the male germline elevates the prevalence of genetic disorders and increases polymorphism levels,masking the effect of negative selection in human populations.
基金National Natural Science Foundation of China(Grant Nos.32070838 and 82301874)Open Fund of State Key Laboratory of Reproductive Medicine,Nanjing Medical University(Grant No.SKLRM K202102)。
文摘Meiotic resumption in mammalian oocytes involves nuclear and organelle structural changes,notably the chromatin configuration transition from a non-surrounding nucleolus(NSN)to surrounding nucleolus(SN)in germinal vesicle oocytes.In the current study,we found that nuclear speckles(NSs),a subnuclear structure mainly composed of serine-arginine(SR)proteins,changed from a diffuse spotted distribution in mouse NSN oocytes to an aggregated pattern in SN oocytes.We also found that the SR protein-specific kinase 1(SRPK1),an enzyme that phosphorylates SR proteins,co-localized with NSs at the SN stage,and that NSN oocytes failed to transition to SN oocytes after the inhibition of SRPK1 activity.Furthermore,the typical structure of the chromatin ring around the nucleolus in SN oocytes collapsed after treatment with an SRPK1 inhibitor.Mechanistically,phosphorylated SR proteins were found to be related to chromatin as shown by a salt extraction experiment,and in situ DNaseⅠassay showed that the accessibility of chromatin was enhanced in SN oocytes when SRPK1 was inhibited,accompanied by a decreased repressive modification on histone and the abnormal recurrence of a transcriptional signal.In conclusion,our results indicated that SRPK1-regulated phosphorylation of SR proteins was involved in the NSN-SN transition and played an important role in maintaining the condensed nucleus of SN oocytes via interacting with chromatin.
