Immunization of male mice with B-cell epitopes in transmembrane domains of CatSper1 inhibits fertility

Li, Honggang; Ding, Xiaofang; Guo, Cuicui; Guan, Huang-Tao; Xiong, Chengliang

doi:10.1016/j.fertnstert.2011.11.043

Cited by 23 publications

(21 citation statements)

References 35 publications

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“…Three weeks after injection, five mice of each group were selected and western blots were performed as described previously 24. Total testis tissue protein was rinsed twice with PBS and homogenized using a lysis buffer (Roche Applied Science, Indianapolis, USA).…”

Section: Methodsmentioning

confidence: 99%

Enhancement of mouse germ cell-associated genes expression by injection of human umbilical cord mesenchymal stem cells into the testis of chemical-induced azoospermic mice

et al. 2014

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Various methods are currently under investigation to preserve fertility in males treated with high-dose chemotherapy and radiation for malignant and nonmalignant disorders. Human umbilical cord mesenchymal stem cells (HUC-MSCs), which possess potent immunosuppressive function and secrete various cytokines and growth factors, have the potential clinical applications. As a potential alternative, we investigate whether injection of HUC-MSCs into the interstitial compartment of the testes to promote spermatogenic regeneration efficiently. HUC-MSCs were isolated from different sources of umbilical cords and injected into the interstitial space of one testis from 10 busulfan-treated mice (saline and HEK293 cells injections were performed in a separate set of mice) and the other testis remained uninjected. Three weeks after MSCs injection, Relative quantitative reverse transcription polymerase chain reaction was used to identify the expression of 10 of germ cell associated, which are all related to meiosis, demonstrated higher levels of spermatogenic gene expression (2–8 fold) in HUC-MSCs injected testes compared to the contralateral uninjected testes (five mice). Protein levels for germ cell-specific genes, miwi, vasa and synaptonemal complex protein (Scp3) were also higher in MSC-treated testes compared to injected controls 3 weeks after treatment. However, no different expression was detected in saline water and HEK293 cells injection control group. We have demonstrated HUC-MSCs could affect mouse germ cell-specific genes expression. The results also provide a possibility that the transplanted HUC-MSCs may promote the recovery of spermatogenesis. This study provides further evidence for preclinical therapeutic effects of HUC-MSCs, and explores a new approach to the treatment of azoospermia.

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Section: Methodsmentioning

confidence: 99%

Enhancement of mouse germ cell-associated genes expression by injection of human umbilical cord mesenchymal stem cells into the testis of chemical-induced azoospermic mice

et al. 2014

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“…Development of contraceptive vaccines for males is of great importance for global population control. Up to the present, many efforts have been put into developing male contraceptive vaccines 4725. Although the hormonal approach to male contraception has made significant progress in the last decade, it has encountered bottlenecks because of the non-ignorable side effects 262728.…”

Section: Discussionmentioning

confidence: 99%

“…Although the hormonal approach to male contraception has made significant progress in the last decade, it has encountered bottlenecks because of the non-ignorable side effects 262728. Scientists have switched to hormone-based targets or sperm-specific molecules,252930 but none of these studies have yet produced a successful contraceptive agent.…”

Section: Discussionmentioning

confidence: 99%

The preparation and application of N-terminal 57 amino acid protein of the follicle-stimulating hormone receptor as a candidate male contraceptive vaccine

Yang

et al. 2014

Asian J Androl

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Follicle-stimulating hormone receptor (FSHR), which is expressed only on Sertoli cells and plays a key role in spermatogenesis, has been paid attention for its potential in male contraception vaccine research and development. This study introduces a method for the preparation and purification of human FSHR 57-amino acid protein (FSHR-57aa) as well as determination of its immunogenicity and antifertility effect. A recombinant pET-28a(+)-FSHR-57aa plasmid was constructed and expressed in Escherichia coli strain BL21 Star™ (DE3) and the FSHR-57aa protein was separated and collected by cutting the gel and recovering activity by efficient refolding dialysis. The protein was identified by Western blot and high-performance liquid chromatography analysis with a band of nearly 7 kDa and a purity of 97.4%. Male monkeys were immunized with rhFSHR-57aa protein and a gradual rising of specific serum IgG antibody was found which reached a plateau on day 112 (16 weeks) after the first immunization. After mating of one male with three female monkeys, the pregnancy rate of those mated with males immunized against FSHR-57aa was significantly decreased while the serum hormone levels of testosterone and estradiol were not disturbed in the control or the FSHR-57aa groups. By evaluating pathological changes in testicular histology, we found that the blood-testis barrier remained intact, in spite of some small damage to Sertoli cells. In conclusion, our study demonstrates that the rhFSHR-57aa protein might be a feasible male contraceptive which could affect sperm production without disturbing hormone levels.

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“…Immunization of female mice with synthetic peptides corresponding to predicted B-cell epitopes in the extracellular part of the transmembrane domains and pore region of CatSper1 that share high identity at aa level between mouse and human CatSper1 led to inhibition of fertility. 84 The sperm from immunized animals showed impaired ability to fertilize eggs in-vitro.…”

Section: Catsper1mentioning

confidence: 99%

Milestones in contraceptive vaccines development and hurdles in their application

Gupta

Shrestha

Minhas

2013

Human Vaccines & Immunotherapeutics

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Immunization of male mice with B-cell epitopes in transmembrane domains of CatSper1 inhibits fertility

Cited by 23 publications

References 35 publications

Enhancement of mouse germ cell-associated genes expression by injection of human umbilical cord mesenchymal stem cells into the testis of chemical-induced azoospermic mice

Enhancement of mouse germ cell-associated genes expression by injection of human umbilical cord mesenchymal stem cells into the testis of chemical-induced azoospermic mice

The preparation and application of N-terminal 57 amino acid protein of the follicle-stimulating hormone receptor as a candidate male contraceptive vaccine

Milestones in contraceptive vaccines development and hurdles in their application

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