scholarly journals MiR-378b Modulates Chlamydia-Induced Upper Genital Tract Pathology

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 566
Author(s):  
Stephanie R. Lundy ◽  
Kobe Abney ◽  
Debra Ellerson ◽  
Joseph U. Igietseme ◽  
Darin Carroll ◽  
...  

Genital Chlamydia trachomatis infection causes severe reproductive pathologies such as salpingitis and pelvic inflammatory disease that can lead to tubal factor infertility. MicroRNAs (miRNAs) are evolutionarily conserved regulators of mammalian gene expression in development, immunity and pathophysiologic processes during inflammation and infection, including Chlamydia infection. Among the miRNAs involved in regulating host responses and pathologic outcome of Chlamydia infection, we have shown that miR-378b was significantly differentially expressed during primary infection and reinfection. In this study, we tested the hypothesis that miR-378b is involved in the pathological outcome of Chlamydia infection. We developed miR-378b knockout mice (miR-378b−/−) using Crispr/Cas and infected them along with their wild-type (WT) control with Chlamydia to compare the infectivity and reproductive pathologies. The results showed that miR-378b−/− mice were unable to clear the infection compared to WT mice; also, miR-378b−/− mice exhibited a relatively higher Chlamydia burden throughout the duration of infection. However, gross pathology results showed that miR-378b−/− mice had significantly reduced uterine dilatations and pathologic lesions after two infections compared to WT mice. In addition, the pregnancy and fertility rates for infected miR-378b−/− mice showed protection from Chlamydia-induced infertility with fertility rate that was comparable to uninfected WT mice. These results are intriguing as they suggest that miR-378b is important in regulating host immune responses that control Chlamydial replication and drive the inflammation that causes complications such as infertility. The finding has important implications for biomarkers of Chlamydial complications and targets for prevention of disease.

2021 ◽  
pp. sextrans-2021-054992
Author(s):  
Jan E A M van Bergen ◽  
Bernice Maria Hoenderboom ◽  
Silke David ◽  
Febe Deug ◽  
Janneke C M Heijne ◽  
...  

ObjectivesThe clinical and public health relevance of widespread case finding by testing for asymptomatic chlamydia infections is under debate. We wanted to explore future directions for chlamydia control and generate insights that might guide for evidence-based strategies. In particular, we wanted to know the extent to which we should pursue testing for asymptomatic infections at both genital and extragenital sites.MethodsWe synthesised findings from published literature and from discussions among national and international chlamydia experts during an invitational workshop. We described changing perceptions in chlamydia control to inform the development of recommendations for future avenues for chlamydia control in the Netherlands.ResultsDespite implementing a range of interventions to control chlamydia, there is no practice-based evidence that population prevalence can be reduced by screening programmes or widespread opportunistic testing. There is limited evidence about the beneficial effect of testing on pelvic inflammatory disease prevention. The risk of tubal factor infertility resulting from chlamydia infection is low and evidence on the preventable fraction remains uncertain. Overdiagnosis and overtreatment with antibiotics for self-limiting and non-viable infections have contributed to antimicrobial resistance in other pathogens and may affect oral, anal and genital microbiota. These changing insights could affect the outcome of previous cost–effectiveness analysis.ConclusionThe balance between benefits and harms of widespread testing to detect asymptomatic chlamydia infections is changing. The opinion of our expert group deviates from the existing paradigm of ‘test and treat’ and suggests that future strategies should reduce, rather than expand, the role of widespread testing for asymptomatic chlamydia infections.


2019 ◽  
Vol 77 (3) ◽  
Author(s):  
Rami Mazraani ◽  
Peter Timms ◽  
Philip C Hill ◽  
Tamaailau Suaalii-Sauni ◽  
Tavita Niupulusu ◽  
...  

ABSTRACT Serological assays can be used to investigate the population burden of infection and potentially sequelae from Chlamydia. We investigated the PGP3 ELISA as a sero-epidemiological tool for infection or sub-fertility in Australian and Samoan women. The PGP3 ELISA absorbance levels were compared between groups of women with infertility, fertile, and current chlamydial infections. In the Australian groups, women with chlamydial tubal factor infertility had significantly higher absorbance levels in the PGP3 ELISA compared to fertile women (P < 0.0001), but not when compared to women with current chlamydial infection (P = 0.44). In the Samoan study, where the prevalence of chlamydial infections is much higher there were significant differences in the PGP3 ELISA absorbance levels between chlamydial sub-fertile women and fertile women (P = 0.003). There was no difference between chlamydial sub-fertile women and women with a current infection (P = 0.829). The results support that the PGP3 assay is effective for sero-epidemiological analysis of burden of infection, but not for evaluation of chlamydial pathological sequelae such as infertility.


2015 ◽  
Vol 73 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Ivan Branković ◽  
Eleanne F. van Ess ◽  
Marlies P. Noz ◽  
Wilhelmina (Anke) J. Wiericx ◽  
Joke Spaargaren ◽  
...  

2019 ◽  
pp. sextrans-2018-053778 ◽  
Author(s):  
Bernice M Hoenderboom ◽  
Birgit H B van Benthem ◽  
Jan E A M van Bergen ◽  
Nicole H T M Dukers-Muijrers ◽  
Hannelore M Götz ◽  
...  

ObjectivesA better understanding of Chlamydia trachomatis infection (chlamydia)–related sequelae can provide a framework for effective chlamydia control strategies. The objective of this study was to estimate risks and risk factors of pelvic inflammatory disease (PID), ectopic pregnancy and tubal factor infertility (TFI) with a follow-up time of up until 8 years in women previously tested for chlamydia in the Chlamydia Screening Implementation study (CSI) and participating in the Netherlands Chlamydia Cohort Study (NECCST).MethodsWomen who participated in the CSI 2008–2011 (n=13 498) were invited in 2015–2016 for NECCST. Chlamydia positive was defined as a positive CSI-PCR test, positive chlamydia serology and/or self-reported infection (time dependent). Data on PID, ectopic pregnancy and TFI were collected by self-completed questionnaires. Incidence rates and HRs were compared between chlamydia-positive and chlamydia-negative women corrected for confounders.ResultsOf 5704 women included, 29.5% (95% CI 28.3 to 30.7) were chlamydia positive. The incidence rate of PID was 1.8 per 1000 person-years (py) (1.6 to 2.2) overall, 4.4 per 1000 py (3.3 to 5.7) among chlamydia positives compared with 1.4 per 1000 py (1.1 to 1.7) for chlamydia negatives. For TFI, this was 0.4 per 1000 py (0.3 to 0.5) overall, 1.3 per 1000 py (0.8 to 2.1) and 0.2 per 1000 py (0.1 to 0.4) among chlamydia positives and negatives, respectively. And for ectopic pregnancy, this was 0.6 per 1000 py (0.5 to 0.8) overall, 0.8 per 1000 py (0.4 to 1.5) and 0.6 per 1000 py (0.4 to 0.8) for chlamydia negatives. Among chlamydia-positive women, the strongest risk factor for PID was symptomatic versus asymptomatic infection (adjusted HR 2.88, 1.4 to 4.5) and for TFI age <20 versus >24 years at first infection (HR 4.35, 1.1 to 16.8).ConclusionWe found a considerably higher risk for PID and TFI in chlamydia-positive women, but the incidence for ectopic pregnancy was comparable between chlamydia-positive and chlamydia-negative women. Overall, the incidence rates of sequelae remained low.Trial registrationNTR-5597.


Author(s):  
Damla C. GONULLU ◽  
Xiao M. HUANG ◽  
LeRoy G. ROBINSON ◽  
Christopher A. WALKER ◽  
Martins AYOOLA-ADEOLA ◽  
...  

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
R Heidenberg ◽  
A Lanes ◽  
E Ginsburg ◽  
C Gordon

Abstract Study question How do live birth rates differ in anovulatory women with polycystic ovary syndrome and hypothalamic hypogonadism compared to normo-ovulatory women undergoing fresh or frozen embryo transfer? Summary answer Live birth rates are similar among all groups undergoing fresh embryo transfer but are significantly lower in women with hypothalamic hypogonadism undergoing frozen embryo transfer. What is known already Conflicting data exist regarding pregnancy outcomes in patients with tubal factor infertility versus polycystic ovary syndrome (PCOS). Some studies demonstrate higher pregnancy and live birth rates for women with PCOS undergoing fresh embryo transfer, but other studies demonstrate no difference. Women with PCOS have higher live birth rates than those with tubal factor infertility when undergoing frozen embryo transfer. Fewer data are available regarding IVF outcomes in women with hypothalamic hypogonadism (HH) and tubal factor infertility. Several studies report comparable live birth rates with fresh embryo transfer, but there are no data on frozen embryo transfer outcomes. Study design, size, duration Retrospective cohort study of all fresh and frozen autologous embryo transfers performed for patients with oligo-anovulation (PCOS, n = 380 and HH, n = 39) and normo-ovulation (tubal factor infertility, n = 315) from 1/1/2012 to 6/30/2019. A total of 734 transfers from 653 patients were analyzed. Participants/materials, setting, methods Transfer outcomes, including implantation, miscarriage, clinical pregnancy and live birth rates, were assessed in fresh and frozen embryo transfer cycles. Adjusted relative risks (RR) and 95% confidence intervals (CI) were calculated adjusting for age, BMI, stimulation protocol, number of embryos transferred, embryo quality, endometrial stripe thickness and day of transfer. Poisson regression was used for counts and with an offset for ratios. Generalized estimating equations were used to account for patients contributing multiple cycles. Main results and the role of chance For fresh embryo transfer cycles, live birth rates are similar among patients with tubal factor infertility, PCOS and HH (29.5% vs. 37.9% vs. 35.9%, respectively, aRR 1.15 95% CI: 0.91–1.44 and aRR 1.23 95% CI: 0.81–2.00, respectively). When evaluating frozen embryo transfer cycles, patients with HH have lower live birth rates than patients with tubal factor infertility (26.5% vs. 42.6%, aRR 0.54 95% CI: 0.33–0.88) and patients with PCOS (26.5% vs. 46.7%, aRR 0.55 95% CI: 0.34–0.88). Additionally, patients with HH have higher chemical pregnancy rates and miscarriage rates than patients with tubal factor infertility (26.5% vs. 13.0% and 17.7% vs. 6.5%, respectively, RR 2.71 95% CI: 1.27–5.77 and RR 2.03 95% CI: 1.05–3.80, respectively). Point biserial correlation showed no significant correlation between live birth and endometrial stripe thickness in HH patients undergoing frozen embryo transfer (r = 0.028, p-value 0.876). Limitations, reasons for caution This study is limited by its retrospective nature and the small sample size of women with hypothalamic hypogonadism. Additionally, these data represent outcomes from a single academic center, so generalizability of our findings may be limited. Wider implications of the findings: Lower live birth rates for HH patients undergoing frozen embryo transfer cycles are not correlated with endometrial stripe thickness. This may be due to absent gonadotropin signaling on endometrial receptors. A prospective randomized trial of HH patients to modified natural versus programmed frozen embryo transfer would best support this hypothesis. Trial registration number Not applicable


Sign in / Sign up

Export Citation Format

Share Document