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透明带糖蛋白:在生育能力及避孕疫苗研发中的相关性

Zona pellucida glycoproteins: Relevance in fertility and development of contraceptive vaccines.

作者信息

Gupta Satish K

机构信息

Basic Medical Sciences Division, Indian Council of Medical Research, New Delhi, India.

出版信息

Am J Reprod Immunol. 2023 Feb;89(2):e13535. doi: 10.1111/aji.13535. Epub 2022 Mar 15.

Abstract

Mammalian zona pellucida (ZP) is composed of three to four glycoproteins, which plays an important role during fertilization. Mutations in the genes encoding zona proteins are reported in women with empty follicle syndrome, degenerated oocytes and those with an abnormal or no ZP further emphasizing their relevance during fertility. Immunization with either native or recombinant ZP glycoproteins/proteins leads to curtailment of fertility in various animal species. Observed infertility is frequently associated with ovarian pathology characterized by follicular atresia and degenerative changes in ZP, which may be due to oophoritogenic T cell epitope(s) within ZP glycoproteins. To avoid ovarian dystrophy, B cell epitopes of ZP glycoproteins have been mapped by using bio-effective monoclonal antibodies. Immunization with the immunogens encompassing the mapped B cell epitopes by and large led to amelioration of follicular atresia. However, their use for human application will require more rigorous research to establish their safety and reversibility of the contraceptive effect. Nonetheless, to minimize human-animal conflicts, ZP-based contraceptive vaccines have been used successfully in the population management of free-ranging animal species such as feral horses, white-tailed deer and elephants. To control zoonotic diseases, attempts are also underway to control the population of other animal species including stray dogs, which acts as one of the major vectors for the rabies virus.

摘要

哺乳动物透明带(ZP)由三到四种糖蛋白组成,在受精过程中起重要作用。在患有空卵泡综合征、卵母细胞退化以及透明带异常或缺失的女性中,已报道了编码透明带蛋白的基因突变,这进一步强调了它们在生育过程中的相关性。用天然或重组的ZP糖蛋白/蛋白质进行免疫会导致多种动物物种的生育能力下降。观察到的不育症通常与卵巢病理相关,其特征为卵泡闭锁和透明带的退行性变化,这可能是由于ZP糖蛋白中的致卵巢炎T细胞表位所致。为避免卵巢萎缩,已通过使用生物有效的单克隆抗体绘制了ZP糖蛋白的B细胞表位。用包含所绘制的B细胞表位的免疫原进行免疫大体上导致卵泡闭锁得到改善。然而,将它们用于人类应用将需要更严格的研究来确定其安全性和避孕效果的可逆性。尽管如此,为尽量减少人与动物的冲突,基于ZP的避孕疫苗已成功用于野马、白尾鹿和大象等自由放养动物物种的种群管理。为了控制人畜共患病,也正在尝试控制包括流浪狗在内的其他动物物种的数量,流浪狗是狂犬病病毒的主要传播媒介之一。

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