Chlamydia muridarum infection differentially changes smooth muscle contractility and responses to prostaglandins in uterus and cervix

Abstract

20 Chlamydia trachomatis infection is a primary cause of reproductive tract diseases including 21 chronic pelvic pain and infertility. Previous studies showed that this infection alters 22 physiological activities in mouse oviducts. Whether this occurs in the uterus and cervix has 23 never been investigated. This study characterized the physiological activity of the uterus and 24 the cervix in a Chlamydia muridarum (Cmu) mouse model of reproductive tract infection. 25 Uterine or cervix smooth muscle contractility, responses to oxytocin or prostaglandins (PGF2α 26 and PGE 2 ) and mRNA expression of oxytocin and PG receptors were assessed 14 days post 27 infection. Cmu infection did not affect the contractions of the uterine horn but significantly 28 decreased the contraction amplitude of the cervix. Cmu infection did not alter the responses of 29 uterine horn or cervix to oxytocin, however PGF2α induced contractions of the uterine horn, 30 but not the cervix, were significantly increased following Cmu infection. PGE 2 contraction 31 amplitude in both the uterine horn and cervix was unaffected by Cmu infection. An 32 upregulation of Ptgfr and a down-regulation of Ptegr4 mRNA expression was observed in the 33 uterine horn following Cmu infection. These results indicate that Cmu infection alters 34 contractility and prostaglandin signalling in the female reproductive tract but the effects are 35 localised to specific regions. 36 3 37 Author summary 38 Chlamydia trachomatis infection is one of the most commonly reported sexually transmitted 39 infections (STIs) worldwide. The infection is readily treated with antibiotics; however, 40 majority of the patients do not display symptoms meaning that they often miss early treatment 41 for acute infection. This enables the spread of bacteria to the upper reproductive tract and the 42 development of diseases including chronic pelvic pain, pelvic inflammatory disease and 43 subsequent infertility. Recent studies reported altered physiological contraction in the oviducts 44 of Chlamydia infected mice. This directly affects the transportation of oocyte in the oviduct. It 45 is not known if this phenomenon extends to the lower part of the reproductive tract such as the 46 uterus and cervix which has implications for sperm transport and ascension of pathogens 47 towards the oviduct. Here we demonstrate that Chlamydia infection of mice significantly 48 reduced the spontaneous contractile activity in the cervix and altered the response of the uterus 49 to some endogenous signalling molecules (prostaglandins). These results show for the first time 50 that chlamydia infection can alter smooth muscle activity along the reproductive tract in a 51 region-specific manner. 52 53 4 54 Introduction 55 Between 2012 to 2014, Chlamydia trachomatis infection was the most frequently reported 56 sexually transmitted infection in Australia [1]. Whilst in England and the United States,57 Chlamydia trachomatis infection is among the most prevalent sexually transmitted infection 58 reported [2, 3]. It...