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The effect of epigenetic sper. abnor.alities on ear.y embr.ogenesis

Asian Jour.al of Andr.logy 2006年第2期8卷 131-142页

作者： benjamin r. emery Douglas T.Car.el Andr.logy & IVF Labor.tor.es Department of Physiology Depar.ment of Obstetr.cs and Gynecology School of Medicine University of UtahSalt Lake CityUtah 84108USA

Sper. ar. a highly specialized cell type der.ved to deliver.the pater.al haploid genome to the oocyte. The epigenetic, or.gene r.gulator., pr.per.ies and mechanisms of the sper. assist in pr.par.tion of the pater.al genome to contr.bute to embr.ogenesis and the genome of the zygote. Many r.cent studies have addr.ssed the issue of alter.d epigenetic pr.cesses in the sper.. This r.view evaluates the cur.ent under.tanding of DNA damage, chr.mosome aneuploidy, r.duced telomer. length, malfor.ations of the centr.some, genomic impr.nting er.or., alter.d mr.A pr.files, and abnor.al nuclear.packaging in the sper. pr.or.to fer.ilization and the obser.ed effects on embr.ogenesis. Attention has also been given to under.tanding the under.ying etiology of sper. with alter.d epigenetic mechanisms in humans. （Asian J Andr.l 2006 Mar. 8： 131-142）

关键词： embr.ogenesis DNA damage impr.nting aneuploidy telomer. centr.some nuclear.packaging male infer.ility

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Novel UBE2B-associated polymor.hisms in an azoosper.ic / oligozoosper.ic population

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Asian Jour.al of Andr.logy 2008年第3期10卷 461-466页

作者： Ivan Huang benjamin r. emery Gr.g L. Chr.stensen Jeanine Gr.ffin C. Matthew Peter.on Douglas T. Car.ell Division of r.pr.ductive Endocr.nology University of Utah Health Sciences Salt LakeCity Utah 84106 USA Andr.logy and IVF Labor.tor.es University of Utah Health Sciences Salt LakeCity Utah 84106 USA

Aim： To assess whether.abnor.alities exist in the UBE2B gene in a population of infer.ile human males, and to establish biologic plausibility of any discover.d mutations. Methods： We car.ied out polymer.se chain r.action （PCr. amplification and sequence analysis of the 5＇-untr.nslated r.gion and six exons of the UBE2B gene, including flanking intr.nic r.gions, in a gr.up of fer.ile and infer.ile men. Following the identification of a putative pr.moter.r.gion that contained single or.dual tr.plet deletions within a 10-CGG r.peat island, we evaluated the binding affinity of these identified polymor.hisms as compar.d to the wild-type sequence to tr.nscr.ption factor.SP1 using a DNA-pr.tein gel shift assay. r.sults： Ther. was a novel exonic single nucleotide polymor.hism （SNP） noted in exon 4 in 5% of infer.ile men. In silico 3D modeling of the alter.d pr.tein showed an innocuous isoleucine for.valine substitution. Ther. wer. no mutations noted within any of the other.exons. Thr.e novel intr.nic SNPs wer. identified within the fer.ile gr.up, and seven novel intr.nic SNPs identified in the infer.ile gr.up. The DNA-pr.tein gel shift assay noted that both single CGG deletion and double CGG deletion bands had appr.ximately twice the binding affinity compar.d to the wild-type for.SP1. The negative contr.l confir.ed no non-specific pr.tein binding. Conclusion- By themselves, a single or.double CGG deletion is unlikely to pose biologic significance. However. such deletions in this suspected pr.moter.r.gion ar. associated with incr.ased binding affinity for.SP1, and might r.pr.sent one of sever.l factor. r.quir.d for.alter.tion of UBE2B gene expr.ssion.

关键词： UBE2B SP1 sper.atogenesis male infer.ility single nucleotide polymor.hism

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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 Gr.fin 刘丽华 Kenneth I.Aston Luke Simon Timothy G.Jenkins benjamin r.emery Douglas T.Car.ell Andr.logy and IVF Labor.tor.es Division of UrologyDepartment of SurgeryUniversity of Utah School of MedicineSalt Lake City UT 84108USA 河北大学医学部 Depar.ment of Obstetr.cs and Gynecology University of Utah School of MedicineSalt Lake City UT 84108USA Depar.ment 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 nucleotide polymor.hisms,SNPs)位点分别用SIFT、Polyphen-2和Mutation Taster.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(r.61758740,r.141722381)发生了非同义突变SNPs,重度少精子症中1例患者在位点r.61758741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。r.61758740可使PYGO2蛋白第141位蛋氨酸(M)变为异亮氨酸(I),r.61758741使PYGO2蛋白第261位碱性赖氨酸(K)变为酸性谷氨酸(E),r.141722381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,r.141722381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

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The hamster.egg penetr.tion test may decr.ase intr.cytoplasmic sper. injection utilization while maintaining high conventional fer.ilization r.tes

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Asian Jour.al of Andr.logy 2021年第1期23卷 11-15页

作者： Yetunde Ibr.him Br.tt Einer.on Douglas T Car.ell benjamin r.emery Er.ca Johnstone Division of r.pr.ductive Endocr.nology and Infer.ility Department of Obstetrics and GynecologyUniversity of UtahSchool of MedicineSalt Lake CityUT 84132USA Division of Mater.al-Fetal Medicine Department of Obstetrics and GynecologyUniversity of UtahSchool of MedicineSalt Lake CityUT 84132USA Division of Ur.logy Department of SurgeryUniversity of UtahSchool of MedicineSalt Lake CityUT 84132USA Depar.ment of Human Genetics University of UtahSchool of MedicineSalt Lake CityUT 84132USA

This was a cohor. study of in vitr. fer.ilization(IVF)subjects at the Univer.ity of Utah,Salt Lake City(UT,USA)utilizing par.ner.*** wher. both the hamster.egg penetr.tion test(HEPT)and semen analysis wer. per.or.ed within 2 year. pr.or.to IVF cycles wer. str.tified into four.gr.ups based on a nor.al or.an abnor.al HEPT and *** mean conventional and intr.cytoplasmic sper. injection(ICSI)fer.ilization r.tes wer. calculated in each *** per.or.ed a univar.ate analysis on the pr.mar. outcome compar.ng clinically inter.sting *** per.or.ed a cost-effectiveness analysis of a policy of HEPT ver.us univer.al ICSI in couples with an abnor.al *** patients with a nor.al HEPT,ther. was no differ.nce in the mean conventional fer.ilization r.tes between those with a nor.al and an abnor.al *** was no differ.nce in the mean conventional fer.ilization r.tes between subjects with a nor.al mor.hology without a hamster.test and those with a nor.al HEPT without a mor.hology *** 1000 simulated cycles with an abnor.al mor.hology,a policy of HEPT was cost saving compar.d to univer.al ICSI,yet pr.duced similar.fer.ilization *** HEPT is similar.to the Wor.d Health Or.anization edition 5(WHO-5)mor.hology in pr.dicting successful conventional fer.ilization while allowing decr.ased utilization of ICSI.A policy of HEPT for.males with abnor.al mor.hology saves cost in selecting couples for.a fer.ilization method.

关键词： conventional fer.ilization hamster.egg penetr.tion test intr.cytoplasmic sper. injection semen analysis sper. penetr.tion assay

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Pr.ton-pump inhibitor.use does not affect semen luality in subfer.ile men

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Asian Jour.al of Andr.logy 2018年第3期20卷 290-293页

作者： Sor.na Keihani James r.Cr.ig Chong Zhang Angela P Pr.sson Jer.my B Myer. William O Br.nt Kenneth I Aston benjamin r.emery Timothy G Jenkins Douglas T Car.ell James M Hotaling Division of Ur.logy Department of Surgery University of Utah Salt Lake City Utah 84132 USA Division of Epidemiology Department of Internal Medicine University of Utah Salt Lake City Utah 84132 USA Andr.logy and IVF Labor.tor. Department of Surgery (Urology) University of Utah Salt Lake City Utah 84108 USA

Pr.ton-pump inhibitor. （PPIs） ar. among the most widely used dr.gs wor.dwide. PPI use has r.cently been linked to adver.e changes in semen quality in healthy men; however. the effects of PPI use on semen par.meter. r.main lar.ely unknown specifically in cases with male factor.infer.ility. We examined whether.PPI use was associated with detr.mental effects on semen par.meter. in a lar.e population of subfer.ile men. We r.tr.spectively r.viewed data fr.m 12 257 subfer.ile men who had visited our.fer.ility clinic fr.m 2003 to 2013. Patients who r.por.ed using any PPIs for.〉3 months befor. semen sample collection wer. included; 7698 subfer.ile men taking no medication ser.ed as contr.ls. Data wer. gather.d on patient age, medication use, and conventional semen par.meter.; patients taking any known sper.atotoxic medication wer. excluded. Linear.mixed-effect r.gr.ssion models wer. used to test the effect of PPI use on semen par.meter. adjusting for.age. A total of 248 patients （258 samples） used PPIs for.at least 3 months befor. semen collection. In r.gr.ssion models, PPI use （either.as the only medication or.when used in combination with other.nonsper.atotoxic medications） was not associated with statistically significant changes in semen par.meter.. To our.knowledge, this is the lar.est study to compar. PPI use with semen par.meter. in subfer.ile men. Using PPIs was not associated with detr.mental effects on semen quality in this r.tr.spective study.

关键词： infer.ility pr.ton-pump inhibitor. semen analysis sper. quality sper.atozoa

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