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Journal of Reproduction and contraception 2002年第3期13卷 158-164页

作者： Xue zhe WU, Jing yu SHAO, Cui qin CHEN, Yi YANG Yun yu FA, Jian hua LIU, Xiao ai LIU, Yan ru LIU Shanghai Cooperative Research Group for Emergency contraception Shanghai Cooperative Research Group for Emergency contraception

To compare the effectiveness and side effects of various low dose of Mifepristone in combination with Misoprostol and low doses Mifepristone alone in emergency contraception Materials & Methods This is a multi center double blind randomized controlled clinical trial. A total of 899 healthy women were allocated into this study and were randomly divided into 3 groups. They were orally administrated with different emergency contraceptives with 120 h after unprotected intercourse. Group I (n=300) was given 25 mg Mifepristone plus 0.2 mg Misoprostol after 24 h. Group II (n=299) was given 10 mg Mifepristone plus 0.2 mg Misoprostol after 24 h. Group III (n=300) was administrated with 10 mg Mifepristone alone. The effective rates in different groups were calculated with Dixon method. Results Altogether 11 pregnancies occurred, among which 2 cases were in Group I, 2 cases in Group II, and 7 cases were in Group III. After correction with method failure, there was only one case in Group I, 0 case in Group II, and 5 cases in Group III. The contraceptive effectiveness in these groups was 95.5%, 100% and 76.9% respectively. The pregnancy rate was significantly lower in Group I and Group II than that of Group III (P0.05). Conclusion Use of low dose Mifepristone (25 mg or 10 mg) in combination with 0.2 mg Misoprostol was an effective, low side effects and safe treatment regimen for emergency contraception.

关键词： Mifepristone Misoprostol emergency contraceptive

Vasectomy by epithelial curettage without suture or cautery： a pilot study in humans

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Asian Journal of Andrology 2010年第3期12卷 315-321,I0008页

作者： John K. Amory John W. Jessen Charles Muller Richard E. Berger Department of Medicine Center for Research in Reproduction and Contraception University of Washington School of Medicine Seattle WA 98195 USA private Practice Dentistry Seattle WA 98195 USA Department of Urology University of Washington School of Medicine Seattle WA 98195 USA

Curettage of the epithelium of the vas deferens might be a safe and effective method of male sterilization. We conducted a pilot study of vasectomy by epithelial curettage with a novel microcurette called the Vas-X in 12 normal men requesting elective sterilization. Seminal fluid analysis was obtained monthly after the procedure for 6 months. Pain was assessed by questionnaire. Three months after the procedure, all men attained sperm concentrations of less than 0.2 million sperm per mL, and seven were azoospermic. Post-procedural pain was minimal. Nine men ultimately achieved and maintained azoospermia; however, 4 to 6 months after the procedure, sperm concentrations increased in three of the 12 subjects, necessitating repeat vasectomy. Microscopic examination of the vas deferens from these failures revealed re-canalization. Vasectomy by epithelial curettage can result in effective sterilization; however, 1/4 of the subjects were not effectively sterilized by the procedure due to re-canalization of the vas deferens. Epithelial curettage will require further refinement to determine if it is a viable form of vasectomy.

关键词： male contraception male sterilization re-canalization spermatogenesis vas deferens vasectomy failure

Identification of epididymis-specific transcripts in the mouse and rat by transcriptional profiling

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Asian Journal of Andrology 2007年第4期9卷 522-527页

作者： Daniel S. Johnston Terry T. Turner Joshua N. Finger Tracy L. Owtscharuk Gregory S. Kopf Scott A. Jelinsky contraception Women＇s Health and Musculoskeletal Biology Wyeth Research Collegeville PA 19426 USA Department of Urology University of Virginia Health Science System Charlottesville VA 22908 Cell Biology University of Virginia Health Science System Charlottesville VA 22908 USA Biological Technologies Molecular Profiling and Biomarker Discovery Wyeth Research Cambridge MA 02140 USA

As part of our efforts to identify novel contraceptive targets in the epididymis we performed transcriptional profiling on each of the 10 and 19 segments of the mouse and rat epididymidis, respectively, using Affymetrix whole genome microarrays. A total of 17 096 and 16 360 probe sets representing transcripts were identified as being expressed in the segmented mouse and rat epididymal transcriptomes, respectively. Comparison of the expressed murine transcripts against a mouse transcriptional profiling database derived from 22 other mouse tissues identified 77 transcripts that were expressed uniquely in the epididymis. The expression of these genes was further evaluated by reverse transcription polymerase chain reaction （RT-PCR） analysis of RNA from 21 mouse tissues. RT-PCR analysis confirmed epididymis-specific expression of Defensin Beta 13 and identified two additional genes with expression restricted only to the epididymis and testis. Comparison of the 16 360 expressed transcripts in the rat epididymis with data of 21 other tissues from a rat transcriptional profiling database identified 110 transcripts specific for the epididymis. Sixty-two of these transcripts were further investigated by qPCR analysis. Only Defensin 22 （E3 epididymal protein） was shown to be completely specific for the epididymis. In addition, 14 transcripts showed more than 100-fold selective expression in the epididymis. The products of these genes might play important roles in epididymal and/or sperm function and further investigation and validation as contraceptive targets are warranted. The results of the studies described in this report are available at the Mammalian Reproductive Genetics （MRG） Database （http：//mrg. ***/）. （Asian J Androl 2007July; 9： 522-527）

关键词： mouse rat epididymis transcriptional profiling contraception microarray epididymis-specific epididymis-selective

Segment boundaries of the adult rat epididymis limit interstitial signaling by potential paracrine factors and segments lose differential gene expression after efferent duct ligation

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Asian Journal of Andrology 2007年第4期9卷 565-573页

作者： Terry T. Tumer Daniel S. Johnston Scott A. Jelinsky Jose L. Tomsig Joshua N. Finger Department of Urology University of Virginia Health Science System Charlottesville VA 22908 US Cell Biology University of Virginia Health Science System Charlottesville VA 22908 US contraception Women＇s Health and Musculoskeletal Biology Wyeth Research Collegeville PA 19426 USA Biological Technologies Molecular Profiling and Biomarker Discovery Wyeth Research Cambridge MA 02140 USA

The epididymis is divided into caput, corpus and cauda regions, organized into intraregional segments separated by connective tissue septa （CTS）. In the adult rat and mouse these segments are highly differentiated. Regulation of these segments is by endocrine, lumicrine and paracrine factors, the relative importance of which remains under investigation. Here, the ability of the CTS to limit signaling in the interstitial compartment is reviewed as is the effect of 15 days of unilateral efferent duct ligation （EDL） on ipsilateral segmental transcriptional profiles. Inter-segmental microperifusions of epidermal growth factor （EGF）, vascular endothelial growth factor （VEGFA） and fibroblast growth factor 2 （FGF2） increased phosphorylation of mitogen activated protein kinase （MAPK） in segments 1 and 2 of the rat epididymis and the effects of all factors were limited by the CTS separating the segments. Microan＇ay analysis of segmental gene expression determined the effect of 15 days of unilateral EDL on the transcriptome-wide gene expression of rat segments 1-4. Over 11 000 genes were expressed in each of the four segments and over 2 000 transcripts in segment 1 responded to deprivation of testicular lumicrine factors. Segments 1 and 2 of control tissues were the most transcriptionally different and EDL had its greatest effects there. In the absence of lumicrine factors, all four segments regressed to a transcriptionally undifferentiated state, consistent with the less differentiated histology. Deprivation of lumicrine factors could stimulate an individual gene＇s expression in some segments yet suppress it in others. Such results reveal a higher complexity of the regulation of rat epididymal segments than that is generally appreciated. （Asian J Androl 2007 July; 9： 565-573）

关键词： efferent duct ligation dedifferentiation proximal epididymis

Testicular fine-needle aspiration for the assessmen＇ of intratesticular hormone concentrations

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Asian Journal of Andrology 2016年第1期18卷 21-24页

作者： Ada P Lee Mara Y Roth Jean-Jacques Nya-Ngatchou Kat Lin Thomas J Walsh Stephanie T Page Alvin M Matsumoto William J Bremner John K Amory Bradley D Anawalt Department of Medicine University of California San Francisco San Francisco CA USA Department of Medicine and Center for Research in Reproduction and contraception University of Washington Seattle WA USA Department of Obstetrics and Gynecology University of Washington Seattle WA USA Department of Urology University of Washington Seattle WA USA Department of Medicine Geriatric Research Education and Clinical Center VA Puget Sound Health Care System Seattle WA USA.

Measurement of intratesticular sex steroid concentrations in men informs both the development of male hormonal contraceptives and the understanding of male infertility. Given the challenges of using invasive techniques to measure testicular hormone physiology, our group has used a minimally-invasive fine-needle aspiration technique to measure intratesticular hormones in normal healthy men. Herein, we present a post-hoc analysis of the safety and efficacy of testicular fine-needle aspiration （FNA） completed as part of six clinical trials. From 2001 through 2011, a total of 404 procedures were conducted among 163 research volunteers, 85.9% of which were successful in obtaining sufficient fluid for the measurement of intratesticular steroid concentrations. Pain was the most common side effect, with 36.8% of procedures associated with moderate procedural pain and 4.7% with severe procedural pain. Postprocedural pain was uncommon and abated within a few days. Mild local bruising occurred with 14.9% of procedures. Two serious adverse events （0.5%） required surgical intervention. The risk of an adverse event was not associated with age, body mass index, testicular size, or the volume of fluid aspirated. Testicular FNA to obtain fluid for measurement of intratesticular steroid concentrations frequently causes mild to moderate procedural pain, but serious adverse events occur rarely. Testicular FNA has been instrumental for defining human intratesticular hormone physiology and is a minimally-invasive, safe, effective method for obtaining fluid for research on testicular physiology and pathology.

关键词： male contraception physiology reproductive and urinary testis

Structure and function of epididymal protein cysteine-rich secretory protein-1

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Asian Journal of Andrology 2007年第4期9卷 508-514页

作者： Kenneth P. Roberts Daniel S. Johnston Michael A. Nolan Joseph L. Wooters Nicole C. Waxmonsky Laura B. Piehl Kathy M. Ensrud-Bowlin David W. Hamilton Department of Urologic Surgery Cell Biology and Development University of Minnesota Minneapolis MN 55455 contraception Women＇s Health ＆ Musculoskeletal Biology Woman＇s Health Research Institute Wyeth Research Collegeville PA 19426 USA Inflammation Department Molecular Profiling and Biomarker Discovery Wyeth Research Cambridge MA 02140 USA Biological Technologies Molecular Profiling and Biomarker Discovery Wyeth Research Cambridge MA 02140 USA Department of Genetics Cell Biology and Development University of Minnesota Minneapolis MN 55455 USA

Cysteine-rich secretory protein-1 （CRISP-1） is a glycoprotein secreted by the epididymal epithelium. It is a member of a large family of proteins characterized by two conserved domains and a set of 16 conserved cysteine residues. In mammals, CRISP-1 inhibits sperm-egg fusion and can suppress sperm capacitation. The molecular mechanism of action of the mammalian CRISP proteins remains unknown, but certain non-mammalian CRISP proteins can block ion channels. In the rat, CRISP-1 comprises two forms referred to as Proteins D and E. Recent work in our laboratory demonstrates that the D form of CRISP-1 associates transiently with the sperm surface, whereas the E form binds tightly. When the spermatozoa are washed, the E form of CRISP-1 persists on the sperm surface after all D form has dissociated. Cross-linking studies demonstrate different protein-protein interaction patterns for D and E, although no binding partners for either protein have yet been identified. Mass spectrometric analyses revealed a potential post-translational modification on the E form that is not present on the D form. This is the only discernable difference between Proteins D and E, and presumably is responsible for the difference in behavior of these two forms of rat CRISP- 1. These studies demonstrate that the more abundant D form interacts with spermatozoa transiently, possibly with a specific receptor on the sperm surface, consistent with a capacitation-suppressing function during sperm transit and storage in the epididymis, and also confirm a tightly bound population of the E form that could act in the female reproductive tract. （Asian J Androl 2007 July; 9： 508-514）

关键词： cysteine-rich secretory protein-1 epididymis sperm capacitation