title: Nitric oxide synthases and tubal ectopic pregnancies induced by Chlamydia infection: basic and clinical insights.
abstract: 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.
authors.affiliation: Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. ruijin.shao@fysiologi.gu.se
authors.forename: Ruijin
authors.initials: R
authors.lastname: Shao
authors.forename: Sean X
authors.initials: SX
authors.lastname: Zhang
authors.forename: Birgitta
authors.initials: B
authors.lastname: Weijdegård
authors.forename: Shien
authors.initials: S
authors.lastname: Zou
authors.forename: Emil
authors.initials: E
authors.lastname: Egecioglu
authors.forename: Anders
authors.initials: A
authors.lastname: Norström
authors.forename: Mats
authors.initials: M
authors.lastname: Brännström
authors.forename: Håkan
authors.initials: H
authors.lastname: Billig
mesh_terms: D000818:Animals; D002417:Cattle; D002690:Chlamydia Infections / Q000150:complications* / Q000201:enzymology; D002692:Chlamydia trachomatis; D005184:Fallopian Tube Diseases / Q000201:enzymology / Q000382:microbiology / Q000473:pathology; D005187:Fallopian Tubes / Q000201:enzymology* / Q000382:microbiology / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051379:Mice; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000201:enzymology* / Q000453:epidemiology / Q000382:microbiology; D011271:Pregnancy, Ectopic / Q000201:enzymology / Q000453:epidemiology / Q000382:microbiology*; D051381:Rats
chemical_list: D007527:Isoenzymes; D019001:Nitric Oxide Synthase