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用促性腺激素释放激素-I和-II蛋白复合物免疫接种的雄性大鼠的免疫避孕效果。

Immunocontraceptive Effects in Male Rats Vaccinated with Gonadotropin-Releasing Hormone-I and -II Protein Complex.

作者信息

Kim Yong-Hyun, Park Byung-Joo, Ahn Hee-Seop, Han Sang-Hoon, Go Hyeon-Jeong, Lee Joong-Bok, Park Seung-Yong, Song Chang-Seon, Lee Sang-Won, Choi In-Soo

机构信息

Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea.

出版信息

J Microbiol Biotechnol. 2019 Apr 28;29(4):658-664. doi: 10.4014/jmb.1901.01067.

Abstract

Immunocontraception has been suggested as an optimal alternative to surgical contraception in animal species. Many immunocontraceptive vaccines have been designed to artificially produce antibodies against gonadotropin-releasing hormone-I (GnRH-I) which remove GnRH-I from the vaccinated animals. A deficiency of GnRH-I thereafter leads to a lack of gonadotropins, resulting in immunocontraception. In this study, we initially developed three immunocontraceptive vaccines composed of GnRH-I, GnRH-II, and a GnRH-I and -II (GnRHI+ II) complex, conjugated to the external domain of Typhimurium flagellin. As the GnRH-I+II vaccine induced significantly ( < 0.01) higher levels of anti-GnRH-I antibodies than the other two vaccines, we further evaluated its immunocontraceptive effects in male rats. Mean testis weight in rats ( = 6) inoculated twice with the GnRH-I+II vaccine at 2-week intervals was significantly ( < 0.01) lower than in negative control rats at 10 weeks of age. Among the six vaccinated rats, two were non-responders whose testes were not significantly reduced when compared to those of negative control rats. Significantly smaller testis weight ( < 0.001), higher anti-GnRH-I antibody levels ( < 0.001), and lower testosterone levels ( < 0.001) were seen in the remaining four responders compared to the negative control rats at the end of the experiments. Furthermore, seminiferous tubule atrophy and spermatogenesis arrest were found in the testis tissues of responders. Therefore, the newly developed GnRH-I+II vaccine efficiently induced immunocontraception in male rats. This vaccine can potentially also be applied for birth control in other animal species.

摘要

免疫避孕已被认为是动物绝育手术的一种理想替代方法。许多免疫避孕疫苗被设计用于人工产生抗促性腺激素释放激素-I(GnRH-I)的抗体,这些抗体能使接种疫苗的动物体内的GnRH-I减少。GnRH-I的缺乏随后导致促性腺激素的缺乏,从而实现免疫避孕。在本研究中,我们最初开发了三种免疫避孕疫苗,它们分别由GnRH-I、GnRH-II以及GnRH-I和-II(GnRHI+II)复合物与鼠伤寒沙门氏菌鞭毛蛋白的外部结构域偶联而成。由于GnRHI+II疫苗诱导产生的抗GnRH-I抗体水平显著高于其他两种疫苗(<0.01),我们进一步评估了其在雄性大鼠中的免疫避孕效果。每隔2周接种两次GnRHI+II疫苗的大鼠(n = 6),在10周龄时的平均睾丸重量显著低于阴性对照大鼠(<0.01)。在这6只接种疫苗的大鼠中,有2只无反应者,与阴性对照大鼠相比,它们的睾丸重量没有显著减轻。与阴性对照大鼠相比,在实验结束时,其余4只有反应者的睾丸重量显著更小(<0.001)、抗GnRH-I抗体水平更高(<0.001)、睾酮水平更低(<0.001)。此外,在有反应者的睾丸组织中发现了生精小管萎缩和生精停滞。因此,新开发的GnRHI+II疫苗能有效诱导雄性大鼠产生免疫避孕效果。这种疫苗也有可能应用于其他动物物种的生育控制。

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