Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Mol Hum Reprod. 2010 Dec;16(12):907-15. doi: 10.1093/molehr/gaq063. Epub 2010 Jul 20.
Human ectopic pregnancy (EP) remains a common cause of pregnancy-related first trimester death. Nitric oxide (NO) is synthesized from L-arginine by three NO synthases (NOS) in different tissues, including the Fallopian tube. Studies of knockout mouse models have improved our understanding of the function of NOS isoforms in reproduction, but their roles and specific mechanisms in infection-induced tubal dysfunction have not been fully elucidated. Here, we provide an overview of the expression, regulation and possible function of NOS isoforms in the Fallopian tube, highlighting the effects of infection-induced changes in the tubal cellular microenvironment (imbalance of NO production) on tubal dysfunction and the potential involvement of NOS isoforms in tubal EP after Chlamydia trachomatis genital infection. The non-equivalent regulation of tubal NOS isoforms during the menstrual cycle suggests that endogenous ovarian steroid hormones regulate NOS in an isoform-specific manner. The current literature suggests that infection with C. trachomatis induces an inflammatory response that eventually leads to tubal epithelial destruction and functional impairment, caused by a high NO output mediated by inducible NOS (iNOS). Therefore, tissue-specific therapeutic approaches to suppress iNOS expression may help to prevent ectopic implantation in patients with prior C. trachomatis infection of the Fallopian tube.
人类异位妊娠（EP）仍然是妊娠相关早期死亡的常见原因。一氧化氮（NO）是由三种一氧化氮合酶（NOS）在不同组织中从 L-精氨酸合成的，包括输卵管。对基因敲除小鼠模型的研究提高了我们对 NOS 同工型在生殖中的功能的理解，但它们在感染诱导的输卵管功能障碍中的作用和特定机制尚未完全阐明。在这里，我们概述了 NOS 同工型在输卵管中的表达、调节和可能的功能，强调了感染引起的输卵管细胞微环境变化（NO 产生失衡）对输卵管功能障碍的影响，以及 NOS 同工型在沙眼衣原体生殖道感染后输卵管 EP 中的潜在作用。输卵管 NOS 同工型在月经周期中的非等效调节表明，内源性卵巢类固醇激素以同工型特异性的方式调节 NOS。目前的文献表明，沙眼衣原体感染会引发炎症反应，最终导致输卵管上皮细胞破坏和功能障碍，这是由诱导型 NOS（iNOS）介导的高 NO 输出引起的。因此，针对组织特异性的抑制 iNOS 表达的治疗方法可能有助于预防既往感染过沙眼衣原体的输卵管患者的异位植入。
