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Human prot.mines and t.e developing spermat.d: t.eir st.uct.re, funct.on, expression and relat.onshipwit. male infert.lit.

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Asian Journal of Andrology 2003年第4期5卷 315-324页

作者： Vincent.W. Aoki douglas t. carrell Andrology and IVF Laborat.ries Universit. of Ut.h School of Medicine Salt Lake City UT 84108 USAAndrology and IVF Laboratories University of Utah School of Medicine Salt Lake City UT 84108 USA

During spermiogenesis, t.e prot.mine prot.ins play an int.gral role in spermat.d chromat.n compact.on. Recent.research has focused on many facet. of prot.mine biology, including prot.mine gene and prot.in st.uct.re/ f... 详细信息

t.act.During spermiogenesis, t.e prot.mine prot.ins play an int.gral role in spermat.d chromat.n compact.on. Recent.research has focused on many facet. of prot.mine biology, including prot.mine gene and prot.in st.uct.re/ funct.on relat.onships, mechanisms of prot.mine expression regulat.on and involvement.of t.e prot.mines in male fert.lit.. In t.is paper, we review our current.underst.nding of t.e st.uct.re and funct.on of t.e prot.mine-1 (P1) and prot.mine-2 (P2) prot.ins and genes, t.e expression and regulat.on of t.ese genes and t.e relat.onship bet.een t.e prot.mines and male fert.lit.. In addit.on, we offer a brief out.ook on fut.re invest.gat.on int. prot.mine prot.ins.

关键词： prot.mines spermat.ds male infert.lit. spermat.d t.ansit.on prot.ins

Novel UBE2B-associat.d polymorphisms in an azoospermic / oligozoospermic populat.on

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Asian Journal of Andrology 2008年第3期10卷 461-466页

作者： Ivan Huang Benjamin R. Emery Greg L. Christ.nsen Jeanine Griffin C. Mat.hew Pet.rson douglas t. carrell Division of Reproduct.ve Endocrinology University of Utah Health Sciences Salt LakeCity Utah 84106 USA Andrology and IVF Laborat.ries University of Utah Health Sciences Salt LakeCity Utah 84106 USA

Aim： t. assess whet.er abnormalit.es exist.in t.e UBE2B gene in a populat.on of infert.le human males, and t. est.blish biologic plausibilit. of any discovered mut.t.ons. Met.ods： We carried out.polymerase chain react.on （PCR） amplificat.on and sequence analysis of t.e 5＇-unt.anslat.d region and six exons of t.e UBE2B gene, including flanking int.onic regions, in a group of fert.le and infert.le men. Following t.e ident.ficat.on of a put.t.ve promot.r region t.at.cont.ined single or dual t.iplet.delet.ons wit.in a 10-CGG repeat.island, we evaluat.d t.e binding affinit. of t.ese ident.fied polymorphisms as compared t. t.e wild-t.pe sequence t. t.anscript.on fact.r SP1 using a DNA-prot.in gel shift.assay. Result.： t.ere was a novel exonic single nucleot.de polymorphism （SNP） not.d in exon 4 in 5% of infert.le men. In silico 3D modeling of t.e alt.red prot.in showed an innocuous isoleucine for valine subst.t.t.on. t.ere were no mut.t.ons not.d wit.in any of t.e ot.er exons. t.ree novel int.onic SNPs were ident.fied wit.in t.e fert.le group, and seven novel int.onic SNPs ident.fied in t.e infert.le group. t.e DNA-prot.in gel shift.assay not.d t.at.bot. single CGG delet.on and double CGG delet.on bands had approximat.ly t.ice t.e binding affinit. compared t. t.e wild-t.pe for SP1. t.e negat.ve cont.ol confirmed no non-specific prot.in binding. Conclusion- By t.emselves, a single or double CGG delet.on is unlikely t. pose biologic significance. However, such delet.ons in t.is suspect.d promot.r region are associat.d wit. increased binding affinit. for SP1, and might.represent.one of several fact.rs required for alt.rat.on of UBE2B gene expression.

关键词： UBE2B SP1 spermat.genesis male infert.lit. single nucleot.de polymorphism

特发性少精子症和无精子症与Pygo2基因蛋白编码区SNPs的相关性

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遗传 2013年第5期35卷 616-622页

作者：葛少钦 Jeanine Grifin 刘丽华 Kennet. I.Ast.n Luke Simon t.mot.y G.Jenkins Benjamin R.Emery douglas t.carrell Andrology and IVF Laborat.ries Division of UrologyDepartment of SurgeryUniversity of Utah School of MedicineSalt Lake City UT 84108USA 河北大学医学部 Depart.ent.of Obst.t.ics and Gynecology University of Utah School of MedicineSalt Lake City UT 84108USA Depart.ent.of Physiology University of Utah School of MedicineSalt Lake City UT 84108USA

男性不育常伴随精子数量减少。Pygo2基因在染色质重塑的伸长精细胞中表达,其功能受损会导致精子形成阻滞和精子生成减少而引发不育。文章旨在检测引起人特发性少精子症和无精子症的Pygo2基因突变。从77例正常生育力男性和195例特发性少... 详细信息

男性不育常伴随精子数量减少。Pygo2基因在染色质重塑的伸长精细胞中表达,其功能受损会导致精子形成阻滞和精子生成减少而引发不育。文章旨在检测引起人特发性少精子症和无精子症的Pygo2基因突变。从77例正常生育力男性和195例特发性少精子症和无精子症患者静脉血提取DNA,采用聚合酶链式反应-测序方法对Pygo2基因3个蛋白质编码区进行测序对比,非同义单核苷酸多态性(Single nucleot.de polymorphisms,SNPs)位点分别用SIFt.Polyphen-2和Mut.t.on t.st.r软件进行诱发蛋白质结构和表型改变的检测和分析。结果表明,195例患者中,178例(30例轻度或中度少精子症,57例重度少精子症和91例无精子症)基因序列分析报告完好,无精子症中3例患者分别在2个位点(rs61758740,rs141722381)发生了非同义突变SNPs,重度少精子症中1例患者在位点rs61758741发生了非同义突变,3个突变位点在SNPs基因数据库都已有报道,轻度或中度少精子症患者以及正常生育力男性中不存在SNPs。rs61758740可使PYGO2蛋白第141位蛋氨酸(M)变为异亮氨酸(I),rs61758741使PYGO2蛋白第261位碱性赖氨酸(K)变为酸性谷氨酸(E),rs141722381使PYGO2蛋白第240位亲水侧链天冬酰胺(N)变为疏水侧链异亮氨酸(I)。软件分析表明,在所发现的3个SNP非同义突变位点中,rs141722381引起的单个氨基酸改变会导致PYGO2蛋白空间结构破坏和诱发相关疾病。因此,Pygo2基因蛋白质编码序列区SNPs可能是特发性少精子症和无精子症的诱发因素之一,导致男性不育。

关键词：特发性少精子症特发性无精子症 Pygo2基因 SNPs

Epigenet.c marks in zebrafish sperm： insight. int. chromat.n compact.on, maint.nance of pluripot.ncy, and t.e role of t.e pat.rnal genome aft.r fert.lizat.on

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Asian Journal of Andrology 2011年第4期13卷 620-621页

作者： douglas t.carrell Andrology and IVF Laborat.ries Departments of Surgery （Urology） Obstetrics and Gynecology and Physiology University of Utah School of Medicine Salt Lake City UT 84108 USA

Human sperm chromat.n, and t.e sperm of most.mammals, undergoes ext.nsive remodeling during spermiogenesis during which 85%-95% of t.e hist.nes are removed and replaced wit. prot.mines. t.e replacement.of most.hist.nes wit. prot.mines facilit.t.s a t.ght.r packaging of t.e chromat.n t.at.is necessary for normal sperm funct.on, and may help prot.ct.sperm DNA from damage during t.ansport.

关键词： Epigenet.c fert.lizat.on

t.e pat.rnal epigenome and embryogenesis： poising mechanisms for development

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Asian Journal of Andrology 2011年第1期13卷 76-80页

作者： t.mot.y G Jenkins douglas t.carrell Andrology and IVF Laborat.ries Department of Surgery University of Utah Salt Lake City UT 84108 USA Depart.ent.of Obst.t.ics and Gynecology University of Utah School of Medicine Salt Lake City UT 84108 USA Depart.ent.of Physiology University of Utah School of Medicine Salt Lake City UT 84108 USA

t.e scope of pat.rnal cont.ibut.ons during early embryonic development.has long been considered limit.d. Dramat.c changes in chromat.n st.uct.re t.roughout.spermat.genesis have been t.ought.t. leave t.e sperm void of complex layers of epigenet.c regulat.on over t.e DNA blueprint. t.us leaving t.e balance of t.at.regulat.on t. t.e oocyt.. However, recent.work in t.e fields of epigenet.cs and male fact.r infert.lit. has placed t.is long-held, and now cont.oversial dogma, in a new light. Elegant.st.dies invest.gat.ng chromat.n and epigenet.c modificat.ons in t.e developing sperm cell have provided new insight. t.at.may est.blish a more crit.cal role for t.e pat.rnal epigenome in t.e developing embryo. DNA met.ylat.on, hist.ne t.il modificat.ons, t.rget.d hist.ne ret.nt.on and prot.mine incorporat.on int. t.e chromat.n have great.influence in t.e developing sperm cell. Pert.rbat.ons in t.e est.blishment.and/or maint.nance of any of t.ese epigenet.c marks have been demonst.at.d t. affect.fert.lit. st.t.s, ranging in severit. from mild t. cat.st.ophic. Sperm require t.is myriad of chromat.n st.uct.ral changes not.only t. serve a prot.ct.ve role t. DNA t.roughout.spermat.genesis and fut.re delivery t. t.e egg, but.also, it.appears, t. cont.ibut. t. t.e development.l program of t.e fut.re embryo. t.is review will focus on our current.underst.nding of t.e epigenet.cs of sperm. We will discuss sperm-specific chromat.n modificat.ons t.at.result.in genes essent.al t. development.being poised for act.vat.on early in embryonic development. t.e disrupt.on of which may result.in reduced fecundit..

关键词： chromat.n DNA met.ylat.on embryogenesis epigenet.cs hist.ne modificat.on male infert.lit.

A syst.mat.c review and met.-analysis t. det.rmine t.e effect.of sperm DNA damage on in vit.o fert.lizat.on and int.acyt.plasmic sperm inject.on out.ome

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Asian Journal of Andrology 2017年第1期19卷 80-90页

作者： Luke Simon Armand Zini Alina Dyachenko Ant.nio Ciampi douglas t.carrell Depart.ent.of Surgery (Urology) University of Utah School of Medicine Salt Lake City UT USA Division of Urology Department of Surgery St. Mary's Hospital Center St. Mary's Hospital 3830 Lacombe Avenue Montreal Quebec H3T 1M5 Canada Depart.ent.of Human Genet.cs University of Utah School of Medicine Salt Lake City UT USA Depart.ent.of Obst.t.ics and Gynecology University of Utah School of Medicine Salt Lake City UT USA.

Sperm DNA damage is prevalent.among infert.le men and is known t. influence nat.ral reproduct.on. However, t.e impact.of sperm DNA damage on assist.d reproduct.on out.omes remains cont.oversial. Here, we conduct.d a met.-analysis of st.dies on sperm DNA damage （assessed by SCSA, t.NEL, SCD, or Comet.assay） and clinical pregnancy aft.r IVF and/or ICSI t.eat.ent.from MEDLINE, EMBASE, and PUBMED dat.base searches for t.is analysis. We ident.fied 41 art.cles （wit. a t.t.l of 56 st.dies） including 16 IVF st.dies, 24 ICSI st.dies, and 16 mixed （IVF ＋ ICSI） st.dies. t.ese st.dies measured DNA damage （by one of four assays： 23 SCSA, 18 t.NEL, 8 SCD, and 7 Comet. and included a t.t.l of 8068 t.eat.ent.cycles （3734 IVF, 2282 ICSI, and 2052 mixed IVF ＋ ICSI）. t.e combined OR of 1.68 （95% Ch 1.49-1.89; P 〈 0.0001） indicat.s t.at.sperm DNA damage affect. clinical pregnancy following IVF and/or ICSI t.eat.ent. In addit.on, t.e combined OR est.mat.s of IVF （16 est.mat.s, OR = 1.65; 95% CI： 1.34-2.04; P 〈 0.0001）, ICSI （24 est.mat.s, OR = 1.31; 95% Ch 1.08-1.59; P = 0.0068）, and mixed IVF ＋ ICSI st.dies （16 est.mat.s, OR = 2.37; 95% Ch 1.89-2.97; P〈 0.0001） were also st.t.st.cally significant. t.ere is sufficient.evidence in t.e exist.ng lit.rat.re suggest.ng t.at.sperm DNA damage has a negat.ve effect.on clinical pregnancy following IVF and/or ICSI t.eat.ent.

关键词： assist.d reproduct.ve t.chnology out.omes clinical pregnancy met.-analysis sperm DNA damage syst.mat.c review

t.e hamst.r egg penet.at.on t.st.may decrease int.acyt.plasmic sperm inject.on ut.lizat.on while maint.ining high convent.onal fert.lizat.on rat.s

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Asian Journal of Andrology 2021年第1期23卷 11-15页

作者： Yet.nde Ibrahim Bret. Einerson douglas t.carrell Benjamin R Emery Erica Johnst.ne Division of Reproduct.ve Endocrinology and Infert.lit. Department of Obstetrics and GynecologyUniversity of UtahSchool of MedicineSalt Lake CityUT 84132USA Division of Mat.rnal-Fet.l Medicine Department of Obstetrics and GynecologyUniversity of UtahSchool of MedicineSalt Lake CityUT 84132USA Division of Urology Department of SurgeryUniversity of UtahSchool of MedicineSalt Lake CityUT 84132USA Depart.ent.of Human Genet.cs University of UtahSchool of MedicineSalt Lake CityUT 84132USA

t.is was a cohort.st.dy of in vit.o fert.lizat.on(IVF)subject. at.t.e Universit. of Ut.h,Salt.Lake Cit.(Ut.USA)ut.lizing part.er *** where bot. t.e hamst.r egg penet.at.on t.st.HEPt.and semen analysis were performed wit.in 2 years prior t. IVF cycles were st.at.fied int. four groups based on a normal or an abnormal HEPt.and *** mean convent.onal and int.acyt.plasmic sperm inject.on(ICSI)fert.lizat.on rat.s were calculat.d in each *** performed a univariat. analysis on t.e primary out.ome comparing clinically int.rest.ng *** performed a cost.effect.veness analysis of a policy of HEPt.versus universal ICSI in couples wit. an abnormal *** pat.ent. wit. a normal HEPt.t.ere was no difference in t.e mean convent.onal fert.lizat.on rat.s bet.een t.ose wit. a normal and an abnormal *** was no difference in t.e mean convent.onal fert.lizat.on rat.s bet.een subject. wit. a normal morphology wit.out.a hamst.r t.st.and t.ose wit. a normal HEPt.wit.out.a morphology *** 1000 simulat.d cycles wit. an abnormal morphology,a policy of HEPt.was cost.saving compared t. universal ICSI,yet.produced similar fert.lizat.on *** HEPt.is similar t. t.e World Healt. Organizat.on edit.on 5(WHO-5)morphology in predict.ng successful convent.onal fert.lizat.on while allowing decreased ut.lizat.on of ICSI.A policy of HEPt.for males wit. abnormal morphology saves cost.in select.ng couples for a fert.lizat.on met.od.

关键词： convent.onal fert.lizat.on hamst.r egg penet.at.on t.st int.acyt.plasmic sperm inject.on semen analysis sperm penet.at.on assay

Updat.s on t.e relat.on of weight.excess and reproduct.ve funct.on in men： sleep apnea as a new area of int.rest

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Asian Journal of Andrology 2012年第1期14卷 77-81,176,177页

作者： Ahmad O Hammoud douglas t.carrell Mark Gibson C Mat.hew Pet.rson A Wayne Meikle Division of Reproduct.ve Endocrinology and Infert.lit. Department of Obstetrics and Gynecology University of Utah School of Medicine Salt Lake City UT 84108 USA Androiogy and IVF Laborat.ries Department of Surgery （Urology） and Physiology University of Utah School of Medicine Salt Lake City UT 84108 USA Endocrinology/ Diabet.s Research Department of Medicine University of Utah School of Medicine Salt Lake City UT 84132 USA

Obesit. has a negat.ve effect.on male reproduct.ve funct.on. It.is associat.d wit. low t.st.st.rone levels and alt.rat.on in gonadot.opin secret.on. Male obesit. has been linked t. reduced male fert.lit.. Dat. regarding t.e relat.on of obesit. t. sperm paramet.rs are conflict.ng in t.rms of t.e nat.re and magnit.de of t.e effect. New areas of int.rest.are emerging t.at.can help explain t.e variat.on in st.dy result., such as genet.c polymorphism and sleep apnea. Sleep disorders have been linked t. alt.red t.st.st.rone product.on and hypogonadism in men. It.was also correlat.d t. erect.le dysfunct.on. t.e relat.on of sleep disorders t. male fert.lit. and sperm paramet.rs remains t. be invest.gat.d. Men wit. hypogonadism and infert.lit. should be screened for sleep apnea. t.eat.ent.of obesit. and sleep apnea improves t.st.st.rone levels and erect.le funct.on.

关键词： infert.lit. male infert.lit. reproduct.ve funct.on sleep apnea weight.excess

Associat.on of 25-hydroxy-vit.min D levels wit. semen and hormonal paramet.rs

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Asian Journal of Andrology 2012年第6期14卷 855-859页

作者： Ahmad O Hammoud A Wayne Meikle C Mat.hew Pet.rson Joseph St.nford Mark Gibson douglas t.carrell Division of Reproduct.ve Endocrinology and Infert.lit. University of Utah Salt Lake City UT 84108 USA Division of Endocrinology Metabolism and Diabetes Department of Internal Medicine University of Utah School of Medicine Salt Lake City UT 84108 USA ARUP Inst.t.t. for Clinical and Experiment.l Pat.ology Salt Lake City UT 84108 USA Depart.ent.of Prevent.ve and Family Medicine University of Utah Salt Lake City UT 84108 USA Depart.ent.of Surgery (Urology) and Physiology Andrology and IVF Laboratories University of Utah Salt Lake City UT 84108 USA

Vit.min D levels have been linked t. various healt. out.omes including reproduct.ve disorders. t.e purpose of t.is st.dy was t. explore t.e associat.on bet.een serum vit.min D level （25-hydroxy-vit.min D, or 250HD） and semen and hormonal paramet.rs. t.is is a cross-sect.onal st.dy t.at.included 170 healt.y men recruit.d for t.e st.dy of spermat.genesis from t.e general populat.on. Men complet.d general and reproduct.ve healt. quest.onnaires, and donat.d blood and semen samples. t.e main measures were hormonal （t.t.l and free t.st.st.rone, sex hormone-binding globulin, est.adiol, follicle-st.mulat.ng hormone and lut.inizing hormone） and semen paramet.rs, adjust.d （n= 147） for age, body mass index （BMI）, season, alcohol int.ke and smoking, in relat.on t. cat.gories of vit.min D levels, det.rmined apriori. t.e mean age of t.e st.dy populat.on was 29.0±8.5 years and mean BMI was 24.3±3.2 kg m-2. t.e mean 250HD was 34.1± 15.06 ng m1-1. BMI showed a negat.ve associat.on wit. 250HD. Sperm concent.at.on, sperm progressive mot.lit., sperm morphology, and t.t.l progressively mot.le sperm count.were lower in men wit. ‘250HD ≥ 50 ng ml-1＇ when compared t. men wit.‘20 ng ml-1 ≤ 250H D〈 50 ng ml-1,. t.t.l sperm count.and t.t.l progressive mot.le sperm count.were lower in men wit. ‘250HD〈20 ng ml-1＇ when compared t. men wit.‘20 ng ml-1≤250HD〈50 ng ml-1＇. t.e adjust.d means of various hormonal paramet.rs did not.show st.t.st.cal difference in t.e different.cat.gories of 250HD. In conclusion, serum vit.min D levels at.high and low levels can be negat.vely associat.d wit. semen paramet.rs.

关键词： low semen count obesit. semen paramet.rs vit.min D