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Contraceptive and molecular function of a novel recombinant vaccine based human leukemia inhibitory factor on Balb/c mice: An experimental in vivo study.
Journal of Reproductive Immunology ( IF 3.4 ) Pub Date : 2020-08-31 , DOI: 10.1016/j.jri.2020.103195
Fateme Zare 1 , Mohammad Mehdi Amiri 2 , Hossein Hadinedoushan 3 , Mahdi Dehghan-Manshadi 4 , Fatemeh Mansouri 2 , Farzaneh Fesahat 3 , Ali Akbar Saboor-Yaraghi 2
Affiliation  

The functional competence of leukemia inhibitory factor (LIF), as immunocontraceptive vaccine in mice, was investigated. Balb/c mice were divided into two groups of vaccinated and controls. The recombinant human LIF (rhLIF) protein and phosphate buffer saline was emulsified with Freund's adjuvant and injected into vaccinated and control groups, respectively. Theinhibition of implantation was evaluated in mice uterine. The concentration of secreted interferon-γ (IFN-γ) and interleukin (IL)-4 were measured in cultured splenocyte of mice stimulated by rhLIF. The expressions of immune responsive gene 1 (IRG-1), cochlin (COCH), amphiregulin(Ar), and heparin-binding EGF-like growth factor (HB-EGF) genes were determined. Mice were assessed for inhibition of fertility after delivery, reversibility of immune response against rhLIF, and survival rate. Active immunization of mice with rhLIF resulted in reduction of the implantation and fertility rate up to 80.49% and 75%, respectively. All mice produced a high titer of anti-rhLIF antibodies in serums and vaginal fluids washes after 16 weeks; however, these antibodies were cleared from vaginal fluid washes after six months. A significant down-regulation in mRNA levels of IRG-1, Ar and HB-EGF was observed in vaccinated group compared to controls; however, no significant change in the expression profile of cochlin gene was detected. The results showed that rhLIF prevented pregnancy in a high percentage of female mice. Although the immunization of female Balb/c mice with rhLIF inhibited fertility and expression of genes associated with this molecule, further studies are needed to support this protein as a suitable candidate for contraceptive vaccine in mammals.



中文翻译:

基于人白血病抑制因子的新型重组疫苗对 Balb/c 小鼠的避孕和分子功能:一项体内实验研究。

研究了白血病抑制因子(LIF)作为小鼠免疫避孕疫苗的功能能力。Balb/c 小鼠被分为接种组和对照组两组。重组人LIF(rhLIF)蛋白和磷酸盐缓冲盐水用弗氏佐剂乳化,分别注射到疫苗接种组和对照组。在小鼠子宫中评价植入的抑制。在rhLIF刺激的小鼠培养的脾细胞中测量分泌的干扰素 (IFN-γ)和白细胞介素(IL)-4的浓度。免疫应答基因 1 (IRG-1)、cochlin (COCH)、双调蛋白(Ar)和肝素结合 EGF 样生长因子(HB-EGF) 的表达) 基因被确定。评估小鼠分娩后生育能力的抑制、针对rhLIF的免疫反应的可逆性和存活率。用rhLIF 主动免疫小鼠导致着床率和生育率分别降低至80.49% 和75%。16 周后,所有小鼠的血清和阴道分泌液中都产生了高滴度的抗rhLIF 抗体;然而,这些抗体在 6 个月后从阴道冲洗液中清除。与对照组相比,在接种组中观察到IRG-1ArHB-EGF 的mRNA 水平显着下调;然而,cochlin的表达谱没有显着变化基因被检测到。结果表明,rhLIF 在高比例的雌性小鼠中阻止了怀孕。尽管用rhLIF 对雌性Balb/c 小鼠进行免疫接种抑制了与该分子相关的基因的生育能力和表达,但仍需要进一步研究以支持该蛋白质作为哺乳动物避孕疫苗的合适候选物。

更新日期:2020-09-12
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