Spermatogenesis improved by suppressing the high level of endogenous gonadotropins in idiopathic non-obstructive azoospermia: a case control pilot study

Abstract Background Elevated plasma gonadotropins were associated with desensitization of Sertoli and Leydig cells in the male testis. Testis spermatogenesis ability would be improved via inhibiting high endogenous gonadotropin in patients with severe oligozoospermia. Whether it would be beneficial...

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Main Authors: Xuechun Hu, Zheng Ding, Zhiwei Hong, Zhichuan Zou, Yuming Feng, Ruilou Zhu, Jinzhao Ma, Xie Ge, Chaojun Li, Bing Yao
Format: Article
Language:English
Published: BMC 2018-09-01
Series:Reproductive Biology and Endocrinology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12958-018-0401-7
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author Xuechun Hu
Zheng Ding
Zhiwei Hong
Zhichuan Zou
Yuming Feng
Ruilou Zhu
Jinzhao Ma
Xie Ge
Chaojun Li
Bing Yao
author_facet Xuechun Hu
Zheng Ding
Zhiwei Hong
Zhichuan Zou
Yuming Feng
Ruilou Zhu
Jinzhao Ma
Xie Ge
Chaojun Li
Bing Yao
author_sort Xuechun Hu
collection DOAJ
description Abstract Background Elevated plasma gonadotropins were associated with desensitization of Sertoli and Leydig cells in the male testis. Testis spermatogenesis ability would be improved via inhibiting high endogenous gonadotropin in patients with severe oligozoospermia. Whether it would be beneficial for non-obstructive azoospermia (NOA) patients was still unclear. Methods Goserelin, a gonadotropin releasing hormone agonist (GnRHα) was used to suppress endogenous gonadotropin levels (gonadotropin reset) in the NOA patients, improving the sensitization of the Sertoli and Leydig cells. Then human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG) were injected to stimulate them to ameliorate the ability of testicular spermatogenesis. The main outcome measure was the existence of spermatozoa in the semen or by testicular sperm extraction (TESE). Elevation of inhibin B and/or ameliorative expression pattern of ZO-1 was the secondary objective. Results A total of 35 NOA men who failed to retrieve sperm via TESE were enrolled. Among these, 10 patients without treatment were selected as control group and secondary TESE was performed 6 months later. Of the 25 treated men, inhibin B was elevated in 11 patients in the first 4 weeks (Response group), while only 5 patients had constant increase in the following 20 weeks (Response group 2). Of the 5 men, 2 men acquired sperm (Response group 2B), while 3 failed (Response group 2A). Immunofluorescence of mouse vasa homologue (MVH) and ZO-1 showed that both positive MVH signals and ZO-1 expression were significantly increased in the Response group 2, but only Response group 2B showed ameliorative ZO-1 distribution. Conclusions Gonadotropin reset, a new therapeutic protocol with GnRHα, was able to improve the ability of testicular spermatogenesis in the NOA patients through restoring the sensitivity of Sertoli and Leydig cells, which were reflected by elevated inhibin B and ameliorative ZO-1 expression and distribution. Trial registration ClinicalTrials.gov identifier: NCT02544191.
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spelling doaj.art-29e9ea351a294cb2ba09664482c35f762022-12-21T18:21:30ZengBMCReproductive Biology and Endocrinology1477-78272018-09-0116111010.1186/s12958-018-0401-7Spermatogenesis improved by suppressing the high level of endogenous gonadotropins in idiopathic non-obstructive azoospermia: a case control pilot studyXuechun Hu0Zheng Ding1Zhiwei Hong2Zhichuan Zou3Yuming Feng4Ruilou Zhu5Jinzhao Ma6Xie Ge7Chaojun Li8Bing Yao9Center of Reproductive Medicine, Nanjing Jinling Hospital, the Medical School of Nanjing UniversityNanjing Jiangning Hospital, the Affiliated Jiangning Hospital of Nanjing Medical UniversityCenter of Reproductive Medicine, Nanjing Jinling Hospital, the Medical School of Nanjing UniversityCenter of Reproductive Medicine, Nanjing Jinling Hospital, the Medical School of Nanjing UniversityCenter of Reproductive Medicine, Nanjing Jinling Hospital, the Medical School of Nanjing UniversityMOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center and the Medical School of Nanjing University, National Resource Center for Mutant MiceCenter of Reproductive Medicine, Nanjing Jinling Hospital, the Medical School of Nanjing UniversityCenter of Reproductive Medicine, Nanjing Jinling Hospital, the Medical School of Nanjing UniversityMOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center and the Medical School of Nanjing University, National Resource Center for Mutant MiceCenter of Reproductive Medicine, Nanjing Jinling Hospital, the Medical School of Nanjing UniversityAbstract Background Elevated plasma gonadotropins were associated with desensitization of Sertoli and Leydig cells in the male testis. Testis spermatogenesis ability would be improved via inhibiting high endogenous gonadotropin in patients with severe oligozoospermia. Whether it would be beneficial for non-obstructive azoospermia (NOA) patients was still unclear. Methods Goserelin, a gonadotropin releasing hormone agonist (GnRHα) was used to suppress endogenous gonadotropin levels (gonadotropin reset) in the NOA patients, improving the sensitization of the Sertoli and Leydig cells. Then human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG) were injected to stimulate them to ameliorate the ability of testicular spermatogenesis. The main outcome measure was the existence of spermatozoa in the semen or by testicular sperm extraction (TESE). Elevation of inhibin B and/or ameliorative expression pattern of ZO-1 was the secondary objective. Results A total of 35 NOA men who failed to retrieve sperm via TESE were enrolled. Among these, 10 patients without treatment were selected as control group and secondary TESE was performed 6 months later. Of the 25 treated men, inhibin B was elevated in 11 patients in the first 4 weeks (Response group), while only 5 patients had constant increase in the following 20 weeks (Response group 2). Of the 5 men, 2 men acquired sperm (Response group 2B), while 3 failed (Response group 2A). Immunofluorescence of mouse vasa homologue (MVH) and ZO-1 showed that both positive MVH signals and ZO-1 expression were significantly increased in the Response group 2, but only Response group 2B showed ameliorative ZO-1 distribution. Conclusions Gonadotropin reset, a new therapeutic protocol with GnRHα, was able to improve the ability of testicular spermatogenesis in the NOA patients through restoring the sensitivity of Sertoli and Leydig cells, which were reflected by elevated inhibin B and ameliorative ZO-1 expression and distribution. Trial registration ClinicalTrials.gov identifier: NCT02544191.http://link.springer.com/article/10.1186/s12958-018-0401-7Gonadotropin resetNOAGnRHα
spellingShingle Xuechun Hu
Zheng Ding
Zhiwei Hong
Zhichuan Zou
Yuming Feng
Ruilou Zhu
Jinzhao Ma
Xie Ge
Chaojun Li
Bing Yao
Spermatogenesis improved by suppressing the high level of endogenous gonadotropins in idiopathic non-obstructive azoospermia: a case control pilot study
Reproductive Biology and Endocrinology
Gonadotropin reset
NOA
GnRHα
title Spermatogenesis improved by suppressing the high level of endogenous gonadotropins in idiopathic non-obstructive azoospermia: a case control pilot study
title_full Spermatogenesis improved by suppressing the high level of endogenous gonadotropins in idiopathic non-obstructive azoospermia: a case control pilot study
title_fullStr Spermatogenesis improved by suppressing the high level of endogenous gonadotropins in idiopathic non-obstructive azoospermia: a case control pilot study
title_full_unstemmed Spermatogenesis improved by suppressing the high level of endogenous gonadotropins in idiopathic non-obstructive azoospermia: a case control pilot study
title_short Spermatogenesis improved by suppressing the high level of endogenous gonadotropins in idiopathic non-obstructive azoospermia: a case control pilot study
title_sort spermatogenesis improved by suppressing the high level of endogenous gonadotropins in idiopathic non obstructive azoospermia a case control pilot study
topic Gonadotropin reset
NOA
GnRHα
url http://link.springer.com/article/10.1186/s12958-018-0401-7
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