Hyaluronan in cervical epithelia protects against infection-mediated preterm birth.
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ABSTRACT:
SUBMITTER: Akgul Y
PROVIDER: S-EPMC4348952 | biostudies-literature | 2014 Dec
REPOSITORIES: biostudies-literature
Publications
Hyaluronan in cervical epithelia protects against infection-mediated preterm birth.
Akgul Yucel Y Word R Ann RA Ensign Laura M LM Yamaguchi Yu Y Lydon John J Hanes Justin J Mahendroo Mala M
The Journal of clinical investigation 20141110 12
Increased synthesis of cervical hyaluronan (HA) from early to late pregnancy has long been proposed to play an essential role in disorganization of the collagen-rich extracellular matrix to allow for maximal compliance and dilation of the cervix during the birth process. Here, we show that HA is not essential for increased cervical distensibility during late pregnancy. Rather, cervicovaginal HA plays an unanticipated important role in epithelial barrier protection of the lower reproductive tract ...[more]
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Project description:Cervical inflammasome activation and subsequent protease upregulation are potential mechanisms of downstream extracellular matrix disruption in LPS-mediated preterm birth.
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Project description:Preterm birth (PTB), or birth before 37 weeks gestation, is the leading cause of neonatal mortality worldwide. Cervical viral infections have been established as risk factors for PTB in women, although the mechanism leading to increased risk is unknown. Using a mouse model of pregnancy, we determined that intra-vaginal HSV2 infection caused increased rates of preterm birth following an intra-vaginal bacterial infection. HSV2 infection resulted in histological changes in the cervix mimicking cervical ripening, including significant collagen remodeling and increased hyaluronic acid synthesis. Viral infection also caused aberrant expression of estrogen and progesterone receptor in the cervical epithelium. Further analysis using human ectocervical cells demonstrated a role for Src kinase in virus-mediated changes in estrogen receptor and hyaluronic acid expression. In conclusion, HSV2 affects proteins involved in tissue hormone responsiveness, causes significant changes reminiscent of premature cervical ripening, and increases risk of preterm birth. Studies such as this improve our chances of identifying clinical interventions in the future.
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