Abstract

Shift work, performed by approximately 21 million Americans, is irregular or unusual work schedule hours occurring after 6:00 pm. Shift work has been shown to disrupt circadian rhythms and is associated with several adverse health outcomes and chronic diseases such as cancer, gastrointestinal and psychiatric diseases and disorders. It is unclear if shift work influences the complications associated with certain infectious agents, such as pelvic inflammatory disease, ectopic pregnancy and tubal factor infertility resulting from genital chlamydial infection. We used an Environmental circadian disruption (ECD) model mimicking circadian disruption occurring during shift work, where mice had a 6-h advance in the normal light/dark cycle (LD) every week for a month. Control group mice were housed under normal 12/12 LD cycle. Our hypothesis was that compared to controls, mice that had their circadian rhythms disrupted in this ECD model will have a higher Chlamydia load, more pathology and decreased fertility rate following Chlamydia infection. Results showed that, compared to controls, mice that had their circadian rhythms disrupted (ECD) had higher Chlamydia loads, more tissue alterations or lesions, and lower fertility rate associated with chlamydial infection. Also, infected ECD mice elicited higher proinflammatory cytokines compared to mice under normal 12/12 LD cycle. These results imply that there might be an association between shift work and the increased likelihood of developing more severe disease from Chlamydia infection.

Highlights

  • In women are unreported because they are a­ symptomatic[10]

  • The trend in fertility was identical for mice infected at ZT3 and ZT15; the effect of Environmental circadian disruption (ECD) appears milder in mice infected at ZT15 corroborating our earlier work where we showed that the time of day of infection was important in determining the extent of chlamydial pathogenesis

  • We reported that Chlamydia infectivity and pathogenesis in mice increased when mice were infected during the early rest period (ZT3) compared to the early active period (ZT15)

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Summary

Introduction

In women are unreported because they are a­ symptomatic[10]. In the female reproductive tract, disease from genital Chlamydia infection is manifested in several ways such as pelvic inflammatory disease (PID), Salpingitis (inflammation of the fallopian tubes) and tubal factor ­infertility[10]. There are varying levels of severity among women who develop complications regardless of how many times they have been exposed or have become ­reinfected[11,12]. We do not understand why women develop such varying severity in reproductive tract pathology following Chlamydia infection. We had recently reported that the time of day of chlamydial infection was associated with the pathogenesis of Chalmydiasis[13]. We disrupted mouse circadian rhythms by changing the light/ dark (LD) cycle to simulate shift ­work[14,15,16,17] and hypothesized that mice subjected to a weekly 6-h advanced shift in their normal light dark cycle and infected with Chlamydia muridarum (C. muridarum) will show increased infectivity, dysregulated immune profile and increased pathology. We compared infection in the early rest period and active period in these mice with disrupted circadian rhythms

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