BACKGROUND Reproductive tract infection is an important factor leading to male and female infertility. Among female infertility factors, microbial and viral infections are the main factors affecting female reproductive health and causing tubal infertility, ectopic tubal pregnancy and premature delivery. Among male infertility factors, 13-15% of male infertility is related to infection. Defensins are cationic antibacterial and antiviral peptides, classified into α-defensins, β-defensins and θ-defensins. Humans only have α-defensins and β-defensins. Apart from their direct antimicrobial functions, defensins have an immunomodulatory function and are involved in many physiological processes. Studies have shown that defensins are widely distributed in the female reproductive tract (FRT) and male reproductive tract (MRT), playing a dual role of host defence and fertility protection. However, to our knowledge, the distribution, regulation and function of defensins in the reproductive tract and their relation to reproduction have not been reviewed. OBJECTIVE AND RATIONALE This review summarizes the expression, distribution and regulation of defensins in the reproductive tracts to reveal the updated research on the dual role of defensins in host defence and the protection of fertility. SEARCH METHODS A systematic search was conducted in PubMed using the related keywords through April 2022. Related data from original researches and reviews were integrated to comprehensively review the current findings and understanding of defensins in the human reproductive system. Meanwhile, female and male transcriptome data in the GEO database were screened to analyze defensins in the human reproductive tracts. OUTCOMES Two transcriptome databases from the GEO database (GSE7307 and GSE150852) combined with existing researches reveal the expression levels and role of the defensins in the reproductive tracts. In the FRT, a high expression level of α-defensin is found, and the expression levels of defensins in the vulva and vagina are higher than those in other organs. The expression of defensins in the endometrium varies with menstrual cycle stages and with microbial invasion. Defensins also participate in the local immune response to regulate the risk of spontaneous preterm birth. In the MRT, a high expression level of β-defensins is also found. It is mainly highly expressed in the epididymal caput and corpus, indicating that defensins play an important role in sperm maturation. The expression of defensins in the MRT varies with androgen levels, age and the status of microbial invasion. They protect the male reproductive system from bacterial infections by neutralizing lipopolysaccharide and downregulating pro-inflammatory cytokines. In addition, animal and clinical studies have shown that defensins play an important role in sperm maturation, motility and fertilization. WIDER IMPLICATIONS As a broad-spectrum antimicrobial peptide without drug resistance, defensin has great potential for developing new natural antimicrobial treatments for reproductive tract infections. However, increasing evidence has shown that defensins can not only inhibit microbial invasion but can also promote the invasion and adhesion of some microorganisms in certain biological environments, such as human immunodeficiency virus. Therefore, the safety of defensins as reproductive tract anti-infective drugs needs more in-depth research. In addition, the modulatory role of defensins in fertility requires more in-depth research since the current conclusions are based on small-size samples. At present, scientists have made many attempts at the clinical transformation of defensins. However, defensins have problems such as poor stability, low bioavailability and difficulties in their synthesis. Therefore, the production of safe, effective and low-cost drugs remains a challenge.

中文翻译：

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防御素：人类生殖健康的捍卫者。

背景技术生殖道感染是导致男女不育的重要因素。在女性不孕因素中，微生物和病毒感染是影响女性生殖健康并引起输卵管性不孕、异位输卵管妊娠和早产的主要因素。在男性不育因素中，13-15%的男性不育与感染有关。防御素是阳离子抗菌和抗病毒肽，分为α-防御素、β-防御素和θ-防御素。人类只有α-防御素和β-防御素。除了直接的抗菌功能外，防御素还具有免疫调节功能，并参与许多生理过程。研究表明，防御素广泛分布于女性生殖道（FRT）和男性生殖道（MRT），发挥宿主防御和生育保护的双重作用。然而，据我们所知，防御素在生殖道中的分布、调节和功能及其与生殖的关系尚未得到审查。目的和基本原理 本综述总结了防御素在生殖道中的表达、分布和调控，以揭示防御素在宿主防御和生育保护中的双重作用的最新研究。检索方法 截至 2022 年 4 月，使用相关关键词在 PubMed 中进行了系统检索。整合了来自原始研究和综述的相关数据，以全面回顾当前对人类生殖系统防御素的发现和理解。同时，筛选了 GEO 数据库中的女性和男性转录组数据，以分析人类生殖道中的防御素。结果 GEO 数据库中的两个转录组数据库（GSE7307 和 GSE150852）结合现有研究揭示了防御素在生殖道中的表达水平和作用。在FRT中，发现α-防御素的高表达水平，外阴和阴道中防御素的表达水平高于其他器官。子宫内膜中防御素的表达随月经周期阶段和微生物入侵而变化。防御素还参与局部免疫反应以调节自发性早产的风险。在 MRT 中，还发现了 β-防御素的高表达水平。主要在附睾头和附睾体中高表达，表明防御素在精子成熟中起重要作用。MRT 中防御素的表达随雄激素水平、年龄和微生物入侵的状态而变化。它们通过中和脂多糖和下调促炎细胞因子来保护男性生殖系统免受细菌感染。此外，动物和临床研究表明，防御素在精子成熟、活动和受精中发挥重要作用。更广泛的意义 作为一种无耐药性的广谱抗菌肽，防御素在开发针对生殖道感染的新型天然抗菌疗法方面具有巨大潜力。然而，越来越多的证据表明，防御素不仅可以抑制微生物入侵，还可以促进某些微生物在某些生物环境中的入侵和粘附，例如人类免疫缺陷病毒。因此，防御素作为生殖道抗感染药物的安全性需要更深入的研究。此外，防御素对生育的调节作用需要更深入的研究，因为目前的结论是基于小样本。目前，科学家们对防御素的临床转化进行了很多尝试。但防御素存在稳定性差、生物利用度低、合成困难等问题。因此，生产安全、有效和低成本的药物仍然是一个挑战。防御素作为生殖道抗感染药物的安全性需要更深入的研究。此外，防御素对生育的调节作用需要更深入的研究，因为目前的结论是基于小样本。目前，科学家们对防御素的临床转化进行了很多尝试。但防御素存在稳定性差、生物利用度低、合成困难等问题。因此，生产安全、有效和低成本的药物仍然是一个挑战。防御素作为生殖道抗感染药物的安全性需要更深入的研究。此外，防御素对生育的调节作用需要更深入的研究，因为目前的结论是基于小样本。目前，科学家们对防御素的临床转化进行了很多尝试。但防御素存在稳定性差、生物利用度低、合成困难等问题。因此，生产安全、有效和低成本的药物仍然是一个挑战。科学家们对防御素的临床转化进行了多次尝试。但防御素存在稳定性差、生物利用度低、合成困难等问题。因此，生产安全、有效和低成本的药物仍然是一个挑战。科学家们对防御素的临床转化进行了多次尝试。但防御素存在稳定性差、生物利用度低、合成困难等问题。因此，生产安全、有效和低成本的药物仍然是一个挑战。