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Hui Zhu,
Yugui Cui,
Jin Xie,
Ling Chen,
Xiangxiang Chen,
Xuejiang Guo,
Yefei Zhu, Xinghai Wang,
Jiansun Tong,
Zuomin Zhou,
Yue Jia,
Yan-He Lue,
Amiya Sinha Hikim,
Christina Wang,
Ronald S Swerdloff,
Jiahao Sha
PROTEOMICS - CLINICAL APPLICATIONS 04/2011; 5(3-4):191. · 1.81 Impact Factor
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Yiqun Gu,
Xiaowei Liang,
Weixiong Wu,
Minli Liu,
Shuxiu Song,
Lifa Cheng,
Liwei Bo,
Chengliang Xiong, Xinghai Wang,
Xiaozhang Liu,
Lin Peng,
Kangshou Yao
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ABSTRACT: Hormonal male contraceptive regimens effectively and reversibly suppress sperm production, but there are few large-scale efficacy studies.
The safety, contraceptive efficacy, reversibility, and feasibility of injectable testosterone undecanoate (TU) in tea seed oil as a hormonal male contraceptive was assessed.
This was a multicenter, phase III, contraceptive efficacy clinical trial. Participants: A total of 1045 healthy fertile Chinese men were recruited throughout China into the study.
Injections of 500 mg TU were administered monthly for 30 months. A definition of severe oligozoospermia (< or =1 x 10(6)/ml) was used as a criterion of spermatogenic suppression and as the threshold for entering the contraceptive efficacy phase.
The primary outcome was pregnancy rate in the partner. Other outcomes include: semen parameters, testis volumes, reproductive hormone levels, and safety laboratory tests.
Forty-three participants (4.8%) did not achieve azoospermia or severe oligozoospermia within the 6-month suppression phase. A total of 855 participants entered into the efficacy phase, and 733 participants completed monthly TU treatment and follow-up. There were nine pregnancies in 1554.1 person-years of exposure in the 24-month efficacy phase for a cumulative contraceptive failure rate of 1.1 per 100 men. The combined method failure rate was 6.1%, comprising 4.8% with inadequate suppression and 1.3% with postsuppression sperm rebound. No serious adverse events were reported. Spermatogenesis returned to the normal fertile reference range in all but two participants.
Monthly injection of 500 mg TU provides safe, effective, reversible, and reliable contraception in a high proportion of healthy fertile Chinese men.
The Journal of clinical endocrinology and metabolism 03/2009; 94(6):1910-5. · 6.50 Impact Factor
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ABSTRACT: Prior studies have demonstrated that combined treatment of testosterone with a progestin induces a more rapid and greater suppression of spermatogenesis than testosterone treatment alone. We hypothesized that the suppressive effects of the combination of testosterone undecanoate (TU) injections plus oral levonorgestrel (LNG) on spermatogenesis may be mediated through a greater perturbation of testicular gene expression than TU alone. To test this hypothesis, we performed open testicular biopsy on 12 different adult healthy subjects: 1) four healthy men as controls; 2) four men 2 wk after TU treatment; and 3) four men 2 wk after TU + LNG administration. RNA isolated from biopsies was used for DNA microarray using the Affymetrix Human Genome U133 Plus 2.0 oligonucleotide microarrays. Gene expression with >or=2-fold changes (P < 0.05) compared with control was analyzed using the National Institutes of Health Database for Annotation, Visualization, and Integrated Discovery 2008 resource. The TU treatment altered the gene expression in 109 transcripts, whereas TU + LNG altered the gene expression in 207 transcripts compared with control. Both TU and TU + LNG administration suppressed gene expression of insulin-like 3; cytochrome P450, family 17, subfamily A1 in Leydig cells; and inhibin alpha in Sertoli cells; they increased proapoptotic transcripts BCL2-like 14, insulin-like growth factor-binding protein 3; and they decreased X-linked inhibitor of apoptosis protein. In comparison with TU treatment alone, TU + LNG treatment upregulated insulin-like 6 and relaxin 1, and downregulated RNA-binding protein transcripts. We conclude that TU + LNG administration induces more changes in testicular gene expression than TU alone. This exploratory study provided a novel and valuable database to study the mechanisms of action of hormonal regulation of spermatogenesis in men and identified testicular-specific molecules that may serve as potential targets for male contraceptive development.
Biology of Reproduction 12/2008; 80(3):484-92. · 4.01 Impact Factor
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Yugui Cui,
Hui Zhu,
Yefei Zhu,
Xuejiang Guo,
Ran Huo, Xinghai Wang,
Jiansun Tong,
Lixin Qian,
Zuomin Zhou,
Yue Jia,
Yan-He Lue,
Amiya Sinha Hikim,
Christina Wang,
Ronald S Swerdloff,
Jiahao Sha
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ABSTRACT: Treatment with injectable testosterone undecanoate (TU) alone or in combination with oral levonorgestrel (LNG) resulted in marked decreases in sperm concentrations. In this study, we used proteomic analyses to examine the cellular/molecular events occurring in the human testis after TU or TU + LNG treatment. We conducted a global proteomic analysis of the human testicular biopsies before and at 2 weeks after TU alone or TU + LNG treatment. Proteins showing significant changes in expression were identified and analyzed. As a result, 17 and 46 protein spots were found with significant differential expression after the treatment with TU alone and TU + LNG, respectively. TU treatment changed the expression of heterogeneous nuclear ribonucleoprotein K (hnRNP K), proteasome inhibitor PI31 subunit (PSMF1), and superoxide dismutase [Mn] mitochondrial precursor (SOD2). These proteins inhibit "assembly", induce cell death, and promote compensatory "cell survival" in the testis. After TU + LNG treatment, "proliferation/cell survival" and "apoptosis/death" were the predominant responses in the testis. TU + LNG treatment inhibited the expression of Prolyl 4-hydroxylase beta subunit (P4HB) and Annexin A2 (Annexin II). These proteins are involved in apoptosis and cell proliferation, respectively. TU + LNG treatment also enhanced the expression of SOD2 and Parvalbumin alpha (Pvalb). These two proteins may protect testicular cells against apoptosis/death and promote cell survival. In conclusion, TU and TU + LNG treatments suppress spermatogenesis through different pathways by changing the expression of different proteins. hnRNP K, PSMF1, SOD2, P4HB, Annexin II, and Pvalb, are key proteins that may be early molecular targets responsible for spermatogenesis suppression induced by hormone treatment.
Journal of Proteome Research 10/2008; 7(9):3984-93. · 5.11 Impact Factor
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ABSTRACT: To observe depot medroxyprogesterone acetate (DMPA) and testosterone undecanoate (TU) injected at 8-week intervals for the suppression of spermatogenesis in healthy Chinese men.
After screening, 30 healthy volunteers were enrolled and randomly assigned to 3 dosage-groups (n = 10/group): 1000 mg TU (Group A), 1000 mg TU plus 150 mg DMPA (Group B), 1000 mg TU plus 300 mg DMPA (Group C). All dosages were given as intramuscular injections at 8-week intervals. The study consisted of an 8-week control (baseline) period, a 24-week treatment period and a 24-week recovery period.
Consistent azoospermia or severe oligozoospermia was achieved and maintained in all the volunteers during the treatment period, except 2 in the mere TU group who experienced a "rebound" in sperm concentrations. An 8-week regimen of TU plus DMPA at both tested combination dosages effectively suppressed spermatogenesis to azoospermia. All volunteers tolerated the injections; no serious adverse effects were reported.
The lower combined dosage is recommended for further testing in an expanded clinical trial or contraceptive efficacy study.
Zhonghua nan ke xue = National journal of andrology 09/2004; 10(8):572-7, 581.
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ABSTRACT: The circulating renin-angiotensin system (RAS) is well known for its role in the maintenance of blood pressure and electrolyte and fluid homeostasis. However, other local angiotensin-generating systems than the circulating RAS have been found in numerous tissues. The male reproductive system including the testis, epididymis, and prostate has several sites of intrinsic RAS activity. The local RAS in these tissues can be responsive to androgens, fat acid, drugs, and hypoxia. There has been evidence for the involvement of the RAS not only in male reproduction, but also in the development of prostate disease. Besides, the assessment of the local RAS activity may be helpful to the early diagnosis of tumor in the male reproductive system.
Zhonghua nan ke xue = National journal of andrology 09/2004; 10(8):623-6.
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ABSTRACT: To investigate the effect of Trx-LHRH, a new GnRH crasis protein, on antibody production and male reproductive function.
Trx-LHRH produced in vitro with a new crasis gene which crasised Trx gene and GnRH gene together, was used as vaccine, and hydroalaminum base as adjuvant, in adult SD rats. After 5 weeks of the first treatment, the same dosage was used again to enhance the effect of vaccine. Antibody level was measured by ELISA, and androgen level by RIA.
Trx-LHRH induced successfully the polycolonal antibody at the level of 1 :1 280 approximately 2 560 after 4 weeks of the first treatment, and 1 : 2 000 after 6 weeks of the enhanced treatment. Testosterone level was reduced significantly (P < 0.01) by ELISA, but there was reasonable variation among individuals. Sperm count was also reduced by Trx-LHRH treatment.
Trx-LHRH can be used as effective vaccine to induce antibody production, and at the same time, restrain the function of hypothatamas-pituitary-testis axis in vivo.
Zhonghua nan ke xue = National journal of andrology 07/2004; 10(6):426-8.
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ABSTRACT: Testosterone undecanoate (TU) is under phase III clinical trial as a hormonal male contraceptive in China. Sex hormones can modulate the immune system. Female hormonal contraceptives may affect SIV/HIV-1 transmission. To evaluate the safety of TU and to understand whether long-term use of TU for a male contraceptive affects users' immunological features, adult male rats were treated for a 32-week TU-treated phase at the dose of 20 mg TU/kg body weight and a 24-week recovery phase. The reproductive and immunological parameters of 4-6 rats in each subgroup were examined at the stated time point. The mean sperm count and viability in the treated rats were significantly suppressed (p < 0.01). In the TU-treated group: the mean blood leukocyte and lymphocyte counts; the proliferation indexes of T cells from peripheral blood mononuclear cells (PBMC) and spleen; and, of B cells from spleen, as well as the mean counts of blood T, NK, and B cells decreased in comparison with those of control group. These decreases were not significant (p > 0.01). Similarly, the mean serum IgM, IgG, and IgA levels and complement activity in TU-treated rats were lower than those in control group (p > 0.01), and the changes in the antibody levels of the examined genital secretions were not significant (p > 0.01). The changes in the thickness of urethra epithelium, and in secretory component (SC) expression in genitals were not observed in the treated group. These results demonstrated that long-term supraphysiological TU injection did not obviously affect the examined rat immunological parameters.
Immunopharmacology and Immunotoxicology 11/2003; 25(4):627-43. · 1.83 Impact Factor
