Human papillomavirus (HPV) is a sexually transmitted infection common among men and women of reproductive age worldwide. HPV viruses are associated with epithelial lesions and cancers. HPV infections have been shown to be significantly associated with many adverse effects in reproductive function. Infection with HPVs, specifically of high-oncogenic risk types (HR HPVs), affects different stages of human reproduction, resulting in a series of adverse outcomes: 1) reduction of male fertility (male infertility), characterized by qualitative and quantitative semen alterations; 2) impairment of couple fertility with increase of blastocyst apoptosis and reduction of endometrial implantation of trophoblastic cells; 3) defects of embryos and fetal development, with increase of spontaneous abortion and spontaneous preterm birth. The actual molecular mechanism(s) by which HPV infection is involved remain unclear. HPV-associated infertility as Janus, has two faces: one reflecting anti-HPV immunity, and the other, direct pathogenic effects of HPVs, specifically, of HR HPVs on the infected/HPV-replicating cells. Adverse effects observed for HR HPVs differ depending on the genotype of infecting virus, reflecting differential response of the host immune system as well as functional differences between HPVs and their individual proteins/antigens, including their ability to induce genetic instability/DNA damage. Review summarizes HPV involvement in all reproductive stages, evaluate the adverse role(s) played by HPVs, and identifies mechanisms of viral pathogenicity, common as well as specific for each stage of the reproduction process.

中文翻译：

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遗传不稳定性和抗HPV免疫反应是与HPV感染相关的不孕症的驱动因素

人乳头瘤病毒（HPV）是一种性传播感染，在全世界育龄男性和女性中普遍存在。HPV病毒与上皮病变和癌症有关。HPV感染已显示出与生殖功能的许多不良影响显着相关。HPV的感染，特别是高致癌风险类型（HR HPV）的感染，会影响人类生殖的不同阶段，导致一系列不良后果：1）男性生殖力下降（男性不育），其特征是精液发生定性和定量改变；2）夫妇生育力受损，胚泡凋亡增加，滋养层细胞子宫内膜植入减少；3）胚胎缺陷和胎儿发育，伴随自然流产和自然早产的增加。涉及HPV感染的实际分子机制仍不清楚。与HPV相关的不育症，如Janus，有两张面孔：一张反映抗HPV免疫力，另一张反映HPV，特别是HR HPV对感染的/复制HPV的细胞的直接致病作用。观察到的HR HPV的不良反应因感染病毒的基因型而异，反映了宿主免疫系统的差异反应以及HPV与它们各自的蛋白质/抗原之间的功能差异，包括它们诱导遗传不稳定性/ DNA损伤的能力。综述总结了HPV在所有生殖阶段中的参与，评估了HPV发挥的不利作用，并确定了病毒致病性的机制，该机制在生殖过程的每个阶段都是常见的和特定的。