Economic evaluation alongside a clinical trial of near-to-patient testing for sexually transmitted infections.

BACKGROUND: Current clinical care for common bacterial STIs (Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Mycoplasma genitalium (MG)) involves empiric antimicrobial therapy when clients are symptomatic, or if asymptomatic, waiting for laboratory testing and recall if indicated. Near-to-patient testing (NPT) can improve pathogen-specific prescribing and reduce unnecessary or inappropriate antibiotic use in treating sexually transmitted infections (STI) by providing same-day delivery of results and treatment. METHODS: We compared the economic cost of NPT to current clinic practice for managing clients with suspected proctitis, non-gonococcal urethritis (NGU), or as an STI contact, from a health provider's perspective. With a microsimulation of 1000 clients, we calculated the cost per client tested and per STI- and pathogen- detected for each testing strategy. Sensitivity analyses were conducted to assess the robustness of the main outcomes. Costs are reported as Australian dollars (2023). RESULTS: In the standard care arm, cost per client tested for proctitis, NGU in men who have sex with men (MSM) and heterosexual men were the highest at $247.96 (95% Prediction Interval (PI): 246.77-249.15), $204.23 (95% PI: 202.70-205.75) and $195.01 (95% PI: 193.81-196.21) respectively. Comparatively, in the NPT arm, it costs $162.36 (95% PI: 161.43-163.28), $158.39 (95% PI: 157.62-159.15) and $149.17 (95% PI: 148.62-149.73), respectively. Using NPT resulted in cost savings of 34.52%, 22.45% and 23.51%, respectively. Among all the testing strategies, substantial difference in cost per client tested between the standard care arm and the NPT arm was observed for contacts of CT or NG, varying from 27.37% to 35.28%. CONCLUSION: We found that NPT is cost-saving compared with standard clinical care for individuals with STI symptoms and sexual contacts of CT, NG, and MG.

The Urethral Microbiota of Men with and without Idiopathic Urethritis.

Nongonococcal urethritis (NGU) is a common genital tract syndrome in men, and up to 50% of cases are considered idiopathic, i.e., no etiological agent is identified. This poses challenges for clinicians in the diagnosis and treatment of NGU and often results in antibiotic misuse and overuse. Therefore, to identify potential infectious causes of urethritis and inform clinical management of urethritis cases, we characterized and compared the urethral microbiota of men with and without idiopathic urethritis. Participants were derived from a case-control study that examined viral and bacterial pathogens and sexual practices associated with NGU. Men with NGU who tested negative for established causes of NGU (Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, adenoviruses, herpes simplex virus [HSV]-1, and/or HSV-2) were classified as idiopathic cases, and the controls were men reporting no current urethral symptoms. Men provided a urine sample that was used to characterize the urethral microbiota using 16S rRNA gene sequencing. Bacterial taxa associated with idiopathic urethritis were identified using analysis of compositions of microbiomes with bias correction. When stratified by sex of sexual partner, we found that the abundance of Haemophilus influenzae was significantly increased in men who have sex with men with idiopathic urethritis, and the abundance of Corynebacterium was significantly increased in men who have sex with women with idiopathic urethritis. Other taxa, including Ureaplasma, Staphylococcus haemolyticus, Streptococcus pyogenes, Escherichia, and Streptococcus pneumoniae/pseudopneumoniae, dominated the urethral microbiota of idiopathic urethritis cases but not controls, suggesting that these organisms may also contribute to urethritis. Importantly, the taxa we identified represent biologically plausible causes of urethritis and should be prioritized for future study. IMPORTANCE Nongonococcal urethritis (NGU) is the commonest genital tract syndrome in men and is nearly universally presumptively treated with an antibiotic. Common causes of NGU include Chlamydia trachomatis and Mycoplasma genitalium, but in more than 50% of cases, an infectious cause is not identified. In this case-control study, we found that the urethral microbiota composition differed between men with and without idiopathic urethritis and differed by sex of sexual partner. We identified specific bacterial taxa that were associated with idiopathic urethritis, including Haemophilus influenzae and Corynebacterium. These data, together with the finding that key bacterial taxa were found to dominate the urethral microbiota of cases but not controls, suggest that a range of bacteria contribute to urethritis and that these organisms may be influenced by sexual practices. Through identifying the infectious causes of urethritis, we can inform appropriate targeted diagnostic and treatment practices and importantly reduce misuse and overuse of antibiotics.

Chlamydial clinical isolates show subtle differences in persistence phenotypes and growth in vitro.

Urogenital Chlamydia trachomatis infection is the most common sexually transmitted bacterial infection throughout the world. While progress has been made to better understand how type strains develop and respond to environmental stress in vitro, very few studies have examined how clinical isolates behave under similar conditions. Here, we examined the development and persistence phenotypes of several clinical isolates, to determine how similar they are to each other, and the type strain C. trachomatis D/UW-3/Cx. The type strain was shown to produce infectious progeny at a higher magnitude than each of the clinical isolates, in each of the six tested cell lines. All chlamydial strains produced the highest number of infectious progeny at 44 h post-infection in the McCoy B murine fibroblast cell line, yet showed higher levels of infectivity in the MCF-7 human epithelial cell line. The clinical isolates were shown to be more susceptible than the type strain to the effects of penicillin and iron deprivation persistence models in the MCF-7 cell line. While subtle differences between clinical isolates were observed throughout the experiments conducted, no significant differences were identified. This study reinforces the importance of examining clinical isolates when trying to relate in vitro data to clinical outcomes, as well as the importance of considering the adaptations many type strains have to being cultured in vitro.

Are genital examinations necessary for STI screening for female sex workers? An audit of decriminalized and regulated sex workers in Melbourne, Australia.

BACKGROUND: The Victorian legislation prohibits sex workers from working when they have visible anogenital herpes or warts. The aim of this study was to determine the proportion of asymptomatic female sex workers (FSW) diagnosed with anogenital herpes or warts by genital examination. METHODS: We analysed all computerised medical records of consultations with FSW at the Melbourne Sexual Health Centre (MSHC) in 2018. All asymptomatic sex workers were offered screening sexually transmitted infections (STIs) and a genital examination to identify visible anogenital herpes or warts at MSHC. FSW consultations were categorised into either 'asymptomatic' or 'symptomatic' based on the presence of symptoms reported by the FSW to the triage nurse. The proportion of asymptomatic FSW diagnosed with visible anogenital herpes or warts during a routine screening examination was calculated. RESULTS: In 2018, 4055 consultations were provided to 1979 FSW. 3406 of these consultations were asymptomatic and all were examined by an experienced clinician for signs of STIs. Of these 3406 asymptomatic consultations, seven FSW (0.21%, 95% CI: 0.08% to 0.42%) were diagnosed with visible anogenital herpes and/or warts following a genital examination. Four were diagnosed with warts (0.12%, 95% CI: 0.03% to 0.30%), two with herpes (0.06%, 95% CI: 0.01% to 0.21%) and one with both herpes and warts (0.03%, 95% CI: 0.001% to 0.16%). CONCLUSION: Based on these data, approximately 500 asymptomatic FSW would need to be examined to identify one case of anogenital herpes or warts. Genital examinations consume considerable clinical resources, increase the duration of consultations and provide essentially no significant benefit to the mandated testing for gonorrhoea, chlamydia, HIV and syphilis. Our clinic will use self-collected samples and no longer examine FSW who are asymptomatic.

Gardnerella vaginalis Clade Distribution Is Associated With Behavioral Practices and Nugent Score in Women Who Have Sex With Women.

BACKGROUND: Gardnerella vaginalis is detected in women with and without bacterial vaginosis (BV). Identification of 4 G. vaginalis clades raised the possibility that pathogenic and commensal clades exist. We investigated the association of behavioral practices and Nugent Score with G. vaginalis clade distribution in women who have sex with women (WSW). METHODS: Longitudinal self-collected vaginal specimens were analyzed using established G. vaginalis species-specific and clade-typing polymerase chain reaction assays. Logistic regression assessed factors associated with detection of G. vaginalis clades, and multinomial regression assessed factors associated with number of clades. RESULTS: Clades 1, 2, and 3 and multiclade communities (<2 clades) were associated with Nugent-BV. Clade 1 (odds ratio [OR], 3.36; 95% confidence interval [CI], 1.65-6.84) and multiclade communities (relative risk ratio [RRR], 9.51; 95% CI, 4.36-20.73) were also associated with Lactobacillus-deficient vaginal microbiota. Clade 4 was neither associated with Nugent-BV nor Lactobacillus-deficient microbiota (OR, 1.49; 95% CI, 0.67-3.33). Specific clades were associated with differing behavioral practices. Clade 1 was associated with increasing number of recent sexual partners and smoking, whereas clade 2 was associated with penile-vaginal sex and sharing of sex toys with female partners. CONCLUSIONS: Our results suggest that G. vaginalis clades have varying levels of pathogenicity in WSW, with acquisition occurring through sexual activity. These findings suggest that partner treatment may be an appropriate strategy to improve BV cure.

Patterns of sexual behaviour and sexual healthcare needs among transgender individuals in Melbourne, Australia, 2011-2014.

OBJECTIVE: Literature surrounding the healthcare needs of transgender individuals is limited in Australia. This study aimed to investigate the demographic characteristics, risk behaviours and HIV/STI positivity among male-to-female (MTF) and female-to-male (FTM) transgender individuals attending Melbourne Sexual Health Centre (MSHC), Australia, between 2011 and 2014. METHOD: A retrospective cohort analysis for 133 transgender individuals was conducted based on the first visit of individuals to MSHC during the study period. Demographic characteristics, sexual behaviours and HIV/STI positivity were examined. RESULTS: The majority of transgender individuals were single or never married (74%; n=99). Almost half of the individuals (47%; n=62) had ever engaged in sex work during their lifetime. The median number of male sexual partners (MSP) reported in the last 3 months was 1 (IQR: 1-2) and with female sexual partners (FSP) was 2 (IQR: 1-4). For those who reported having sexual partners in the previous 3 months, always using condoms with MSP was 31% (n=22), and that with FSP was 18% (n=2). HIV/STI positivity during the study period was 7% (n=8) for chlamydia, 5% (n=6) for gonorrhoea, 5% (n=5) for syphilis and 1% (n=1) for HIV. Hormone use for reassignment was reported by 63% (n=90) of individuals and reassignment surgery was reported by 27% (n=29+6=35). CONCLUSIONS: Transgender individuals in this study were found to be a diverse group, with a history of sex work being a common feature. These findings indicate that transgender individuals' sexual healthcare needs differ substantially from those in other countries, including the US and Canada. Attention to differences in MTF and FTM transgender persons must be considered in healthcare settings in Australia.

Factors Associated with Bacterial Vaginosis among Women Who Have Sex with Women: A Systematic Review.

BACKGROUND: Women who have sex with women (WSW) have a higher burden of bacterial vaginosis (BV) than heterosexual women; studies of risk factors specific to this population are limited. We summarised current knowledge regarding risk factors for BV among WSW by systematic review. METHODS: This systematic review was conducted according to the PRISMA statement. PUBMED, EMBASE, Web of Science and The Cochrane Library were searched to 31st December, 2014. INCLUSION CRITERIA: 1) WSW included in the study population; 2) accepted BV diagnostic method; 3) investigated or could extrapolate factors(s) associated with BV acquisition, persistence or transmission in WSW specifically by comparing BV positive to BV negative women. Search was limited to English-language publications. RESULTS: A limited number of studies have investigated BV in WSW. Of 71 unique references, 18 full-text articles were assessed and 14 studies fulfilled inclusion criteria. BV was positively associated with higher numbers of female partners, both lifetime and in the three months prior to diagnosis, and confirmed BV in a female partner, but inconsistently associated with partners' BV history or symptoms. BV was not associated with ethnicity, vaginal douching or hormonal contraception. The impact of specific sexual activities, male sexual contact, smoking and the menstrual cycle varied considerably between study populations. CONCLUSION: BV in WSW is associated with increased numbers of recent and past female partners and confirmed BV in a female partner. There are limited studies of BV in WSW populations, and research is needed to further elucidate risk factors for BV among WSW. However these data provide epidemiological evidence that BV risk in women is directly related to exposure to other female partners and a partner with BV, providing support for the concept that BV is likely to be transmitted between women. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42014009536 (PROSPERO).

Factors associated with participation and attrition in a longitudinal study of bacterial vaginosis in Australian women who have sex with women.

OBJECTIVE: A number of social and sexual risk factors for bacterial vaginosis (BV) have been described. It is important to understand whether these factors are associated with non-participation or attrition of participants from longitudinal studies in order to examine potential for recruitment or attrition bias. We describe factors associated with participation and attrition in a 24-month prospective cohort study, investigating incident BV among Australian women who have sex with women. STUDY DESIGN AND SETTING: Participants negative for prevalent BV were offered enrolment in a longitudinal cohort study. Participants self-collected vaginal samples and completed questionnaires 3-monthly to endpoint (BV-positive/BV-negative by 24 months). Factors associated with participation in the cohort study were examined by logistic regression and factors associated with attrition from the cohort were examined by Cox regression. RESULTS: The cross-sectional study recruited 457 women. 334 BV-negative women were eligible for the cohort and 298 (89%, 95%CI 85, 92) enrolled. Lower educational levels (aOR 2.72, 95%CI 1.09, 6.83), smoking (aOR 2.44, 95%CI 1.13, 5.27), past BV symptoms (aOR 3.42, 95%CI 1.16, 10.10) and prior genital warts (aOR 2.71, 95%CI 1.14, 6.46) were associated with non-participation; a partner co-enrolling increased participation (aOR 3.73, 95%CI 1.43, 9.70). 248 participants (83%, 95%CI 78, 87) were retained to study endpoint (BV-negative at 24 months or BV-positive at any stage). Attrition was associated being <30 yrs (aHR 2.15, 95%CI 1.13, 4.10) and a male partner at enrolment (aHR 6.12, 95%CI 1.99, 18.82). CONCLUSION: We achieved high participation and retention levels in a prospective cohort study and report factors influencing participation and retention of participants over a 24-month study period, which will assist in the design and implementation of future cohort studies in sexual health and disease.

Detection of oral human papillomavirus in HIV-positive men who have sex with men 3 years after baseline: a follow up cross-sectional study.

BACKGROUND: Human papillomavirus (HPV) is a causative agent in oropharyngeal squamous cell carcinoma. The natural history of oral HPV in HIV-positive men who have sex with men (MSM) is unclear. METHODS: Detection of oral human papillomavirus in 173 HIV-positive MSM using oral rinse samples 3 years apart was investigated. HPV DNA was detected by polymerase chain reaction, and genotyped by Roche Linear Array. RESULTS: Of 173 men tested in 2010, 30 had at least one HPV genotype (17%, 95% CI: 12-23), 15 at least one hr-HPV (9%, 95% CI: 5-14) and 8 had HPV 16 (5%, 95% CI: 2-9) detected. In 2013, 33 had at least one HPV genotype (19%, 95% CI: 14-26), 20 had at least one hr-HPV (12%, 95% CI: 7-17) and 7 had HPV 16 (4%, 95% CI: 2-8) detected. Of 30 men at baseline (2010) with any HPV detected, 14 (47%, 95% CI: 28-66) had at least one persistent genotype. Of the 15 men in 2010 with high risk (hr-) HPV, 6 men (40%, 95% CI: 16-68) had at least one persistent hr-HPV genotype. The incidence rate of detection of at least one new HPV genotype was 4.8 per 100 person years (95% CI: 3.1-7.0), of at least one hr-HPV genotype was 3.2 per 100 person years (95% CI: 1.8-5.1) and of HPV 16 was 0.8 per 100 person years (95% CI: 0.2-2.0). The clearance rate was 14.9 per 100 person years (95% CI: 8.2-24.2) for any HPV, 18.2 per 100 person years (95% CI: 8.2-32.7) for hr-HPV and 17.4 per 100 person years (95% CI: 5.0-38.8) for HPV-16. Persistent HPV detection was associated with duration of HIV (OR 1.13 (per additional year), 95% CI: 1.00-1.26) and tonsillectomy (OR 8.17, 95% CI: 1.30-51.40). CONCLUSION: The same oral HPV genotype was detected again after 3 years in nearly half of HIV-positive men who have sex with men.

The influence of behaviors and relationships on the vaginal microbiota of women and their female partners: the WOW Health Study.

BACKGROUND: A community-based study of women who have sex with women (WSW) was performed to determine the burden of bacterial vaginosis (BV), and behavioral factors influencing the vaginal microbiota of women and their female sexual partners (FSPs), as measured by Nugent score (NS). METHODS: In a cross-sectional study of 18-55-year-old WSW recruited nationally, participants completed questionnaires and self-collected vaginal swab samples weekly on 3 occasions. BV was defined as an NS of 7-10. Factors associated with BV, stability of NS category, and concordance of these categories in co-enrolled couples were examined with multivariable logistic regression analysis. RESULTS: A total of 458 participants were recruited; 192 were co-enrolled with their FSP (96 couples). BV was detected in 125 women (27%; 95% confidence interval [CI], 23%-32%). BV was associated with ≥4 lifetime FSPs (adjusted odds ratio [AOR], 1.9; 95% CI, 1.2-3.1), an FSP with BV symptoms (AOR, 2.9; 1.0-8.2) and smoking, with ≥30 cigarettes per week showing greatest odds (AOR, 2.7; 1.5-5.0). Of 428 women returning ≥2 swab samples, 375 (88%) had a stable NS category across all samples, predominantly reflecting normal flora. Co-enrolled WSW were less likely to have BV (31% vs 23%; P = .07), and the majority (70%) were concordant for NS category (κ = 0.47; P ≤ .01), with most concordant for normal flora. Concordant NS category was associated with a relationship of >6 months (AOR, 4.7; 95% CI, 1.4-16.4) and frequent sexual contact (more than once per month; AOR, 2.7; 1.0-7.1). CONCLUSIONS: BV is associated with key behaviors and smoking practices in WSW, but longer-duration, sexually active WSW partnerships support a stable favorable vaginal microbiota.

Introduction of a sexual health practice nurse is associated with increased STI testing of men who have sex with men in primary care.

BACKGROUND: The study objective was to investigate the effect of the introduction of a sexual health practice nurse on HIV and STI testing in a general practice that specialized in gay men's health. METHODS: This observational study compared the proportion of gay and other men who have sex with men (MSM) tested for HIV, syphilis, chlamydia (urethral and anal) and gonorrhoea (anal), or all of the above (defined as a complete set of tests at a single visit), two years before and one year after the nurse was introduced (Clinic A). Clinic B, a general practice which also specialized in gay men's health, but with no sexual health nurse, was used as a control. RESULTS: In Clinic A, amongst HIV negative MSM the proportion of men who had a complete set of HIV and STI tests increased from 41% to 47% (p < 0.01) after the nurse was introduced. Amongst HIV positive MSM attending clinic A there was an increase in the proportion of men who had a complete set of tests after the nurse was introduced from 27% to 43% (p < 0.001). In Clinic B there was no significant increase in testing in the proportion of either HIV negative or HIV positive men who had a complete set of tests over the same time periods. CONCLUSIONS: The introduction of the sexual health practice nurse resulted in significant increases in episodes of complete STI testing among MSM. The effect was most pronounced among HIV positive MSM.

Anal cancers attributed to human papillomavirus are more common in areas in Victoria, Australia, with higher HIV notifications.

BACKGROUND: Anal cancer is more common in men who have sex with men with HIV. We aimed to determine if there was an association between anal squamous cell carcinoma (SCC) and HIV notifications in men in Victoria, Australia, at a population level. METHODS: We calculated the male age-standardised incidence rates for anal SCC, brain cancer and colon cancer for each local government area (LGA) in Victoria from 1982 to 31 December 2010 using the Victorian Cancer Registry. Male HIV rates in each LGA were calculated using the Victorian HIV Registry. RESULTS: There were 288 men diagnosed with anal SCC, 8793 with brain cancer and 23?938 with colon cancer in 57 LGAs. There were 3163 men notified with HIV during the same period in the same LGAs (range: 4-435 per LGA). There was a significant positive correlation (r=0.45, P<0.001, r(2)=0.20) between the age-standardised rate of anal SCC and the rate of HIV notifications in men in each LGA but no correlation between the male age-standardised rate of colon (Pearson's r=-0.11, P=0.40) or brain (r=-0.05, P=0.71) cancers, and the rate of HIV. The rate of anal cancer was ~50% higher in LGAs with the highest HIV notification rate (incidence rate ratio=1.47; 95% confidence interval: 1.10-1.97). CONCLUSIONS: At a population level, about one in five cases (r(2)=0.20) of anal SCCs in men are explained by the rate of HIV notifications in that LGA.

Oral human papillomavirus in men having sex with men: risk-factors and sampling.

BACKGROUND: Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma is becoming more common. We examined prevalence and risk factors for oral HPV among men who have sex with men (MSM) and compared sampling and transport methods. METHODS: In 2010, 500 MSM (249 HIV-positive) attending Melbourne Sexual Health Centre answered a questionnaire, swabbed their mouth and throat and collected a gargled oral rinse sample. Half the oral rinse was transported absorbed in a tampon (to enable postage). HPV was detected by polymerase chain reaction, and genotyped by Roche Linear Array®. Men with HPV 16 or 18 were retested after six months. RESULTS: Any HPV genotype was detected in 19% (95% confidence intervals (CI) 15-25%) of HIV-infected men and 7% (95% CI 4-11%) of HIV-negative men (p<0.001), and HPV 16 was detected in 4.4% (95% CI 2-8%) of HIV-infected men and 0.8% (0.1-2.8%) of HIV-negative men. Oral HPV was associated with: current smoking (adjusted odds ratio (aOR) 2.2 (95%CI: 1.2-3.9)), time since tooth-brushing (aOR per hour 0.87, 95%CI: 0.8-0.96) and number of lifetime tongue-kissing partners aOR 3.2 95%CI: (1.2-8.4) for 26-100 partners and 4.9 95%CI: (1.9-12.5) for>100 partners. Lifetime oral-penile sex partner numbers were significantly associated in a separate model: aOR 2.8(1.2-6.3) for 26-100 partners and 3.2(1.4-7.2) for>100 partners. HPV 16 and 18 persisted in 10 of 12 men after a median six months. Sensitivities of sampling methods compared to all methods combined were: oral rinse 97%, tampon-absorbed oral rinse 69%, swab 32%. CONCLUSIONS: Oral HPV was associated with HIV infection, smoking, recent tooth-brushing, and more lifetime tongue-kissing and oral sex partners. The liquid oral rinse sample was more sensitive than a tampon-absorbed oral rinse or a self-collected swab.

Progesterone withdrawal, and not increased circulating relaxin, mediates the decrease in myometrial relaxin receptor (RXFP1) expression in late gestation in rats.

In pregnant rats, a significant decrease in myometrial relaxin family peptide receptor 1 (RXFP1) expression, indicative of a functional relaxin withdrawal for activation of myometrial contractions, occurs in late gestation and during spontaneous labor. This coincides with the highest level of circulating relaxin and a decrease in progesterone. We investigated the potential regulatory role of these two systemic factors on myometrial RXFP1 expression by examining the effects of the antiprogestin RU486 and a monoclonal antibody against rat relaxin (MCA1) in pregnant rats. Rats were injected with RU486 on Gestational Day (GD) 7, 16, or 19 and were killed on GD 8, 17, or 20. RU486 caused a significant reduction in myometrial RXFP1. Plasma progesterone and 17beta-estradiol levels were increased in RU486-treated animals compared with controls. RU486 treatment also caused significant increases in myometrial Esr1 and Vegf and a decrease in Esr2. MCA1 was administered i.v. to rats from GD 17 to GD 19. On GD 20, no significant effect of MCA1 treatment on myometrial RXFP1 expression was observed compared with controls. Furthermore, there was no change in Esr1 or Esr2. A significant reduction in myometrial Vegf, however, was observed. We suggest that blocking progesterone action with RU486 increases plasma 17beta-estradiol and myometrial Esr1 and results in decreased RXFP1 expression. In summary, myometrial RXFP1 expression is mediated mainly by progesterone and not circulating relaxin in pregnant rats.

Relaxin physiology in the female reproductive tract during pregnancy.

The characteristic functions of relaxin are associated with female reproductive tract physiology. These include the regulation of biochemical processes involved in remodeling the extracellular matrix of the cervix and vagina during pregnancy and rupture of the fetal membranes at term. Such modifications enable the young to move unimpeded through the birth canal and prevent dystocia. However, relaxin's physiological actions are not limited to late gestation. New functions for this peptide hormone in implantation and placentation are also emerging. Relaxin promotes uterine and placental growth and influences vascular development and proliferation in the endometrium. This chapter provides an overview of the current literature on relaxin physiology in the uterus, cervix and vagina of pregnant females and the impact on fetal health. It also outlines the potential mechanisms of relaxin action, particularly in the cervical extracellular matrix and uterine endometrium.

Effects of uteroplacental restriction on the relaxin-family receptors, Lgr7 and Lgr8, in the uterus of late pregnant rats.

The peptide hormone relaxin stimulates uterine growth and endometrial angiogenesis and inhibits myometrial contractions in a variety of species. The receptor for relaxin is a leucine-rich repeat containing G-protein-coupled receptor Lgr7 (RXFP1) that is highly expressed in the myometrium of late pregnant mice, with a significant decrease in receptor density observed at term. The present study first compared the expression of Lgr7 with another relaxin-family receptor Lgr8 (RXFP2) in the uterus and placenta of late pregnant rats. The uterus was separated into endometrial and myometrial components, and the myometrium into fetal and non-fetal sites, for further analysis. We then assessed the response of these receptors to uteroplacental restriction (UPR). Expression of the Lgr7 gene was significantly higher in the uterus compared with the placenta. Within the uterus, on Day 20 of gestation, there was equivalent expression of Lgr7 in fetal and non-fetal sites of the myometrium, as well as in the endometrium v. myometrium. The second receptor investigated, Lgr8, was also expressed in the endometrium and myometrium, but at significantly lower levels than Lgr7. Bilateral ligation of the maternal uterine blood vessels on Day 18 of gestation resulted in uteroplacental restriction, a decrease in fetal weight and litter size, and a significant upregulation in uterine, but not placental, Lgr7 and Lgr8 gene expression in UPR animals compared with controls. These data suggest that both relaxin family receptors are upregulated in response to a reduction in uteroplacental blood flow in rats.