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Updated: Jul 12, 2025
Induction and Validation of Cellular Senescence in Primary Human Cells
Published on: June 20, 2018
Group B streptococcus induces cellular senescence in human amnion epithelial cells through a partial
Hae-Ryung Park1, Kelly A Hogan2, Sean M Harris3
1Department of Environmental Medicine, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA.
Insights
Group B Streptococcus (GBS) infection causes fetal membrane senescence and inflammation via interleukin-1 (IL-1) signaling. This study reveals a paracrine mechanism impacting pregnancy outcomes.
Area of Science:
- Obstetrics and Gynecology
- Infectious Diseases
- Cellular Biology
Background:
- Group B Streptococcus (GBS) infection is a major cause of adverse pregnancy outcomes and neonatal complications.
- The precise mechanisms by which GBS affects the fetal membrane, a critical barrier against infection, remain unclear.
- Understanding GBS-induced changes in the fetal membrane is crucial for developing interventions against pregnancy complications.
Purpose of the Study:
- To investigate the role of GBS in inducing senescence and inflammation in the fetal membrane.
- To elucidate the involvement of the interleukin-1 (IL-1) pathway in GBS-mediated fetal membrane responses.
- To explore the paracrine signaling between choriodecidua and amnion layers in GBS-infected fetal membranes.
Main Methods:
- Analysis of transcriptomic data from GBS-exposed human fetal membranes to identify affected senescence pathways.
- Treatment of primary amnion epithelial cells with GBS-infected choriodecidual conditioned medium, with or without an IL-1 receptor antagonist (IL-1Ra).
- Assessment of senescence (β-galactosidase activity), inflammatory cytokine release (IL-6, IL-8), and cell proliferation.
Main Results:
- GBS exposure was associated with altered senescence-related gene expression in fetal membranes.
- GBS-infected choriodecidual conditioned medium significantly increased senescence and IL-6/IL-8 release in amnion epithelial cells.
- IL-1 receptor blockade with IL-1Ra attenuated GBS-induced senescence and inflammation, confirming IL-1 pathway involvement.
- IL-1α or IL-1β treatment mimicked these effects, and GBS/IL-1 reduced amnion cell proliferation.
Conclusions:
- This study provides the first evidence of GBS-induced senescence in the fetal membrane.
- A paracrine IL-1 signaling pathway between the choriodecidua and amnion layers mediates GBS effects on the fetal membrane.
- Further research is needed to understand GBS pathogenesis in adverse pregnancy outcomes and develop targeted therapies.
Abstract:
Group B streptococcus (GBS) infection is a significant public health concern associated with adverse pregnancy complications and increased neonatal mortality and morbidity. However, the mechanisms underlying the impact of GBS on the fetal membrane, the first line of defense against pathogens, are not fully understood. Here, we propose that GBS induces senescence and inflammatory factors (IL-6 and IL-8) in the fetal membrane through interleukin-1 (IL-1). Utilizing the existing transcriptomic data on GBS-exposed human fetal membrane, we showed that GBS affects senescence-related pathways and genes. Next, we treated primary amnion epithelial cells with conditioned medium from the choriodecidual layer of human fetal membrane exposed to GBS (GBS collected choriodecidual [CD] conditioned medium) in the absence or presence of an IL-1 receptor antagonist (IL-1Ra). GBS CD conditioned medium significantly increased β-galactosidase activity, IL-6 and IL-8 release from the amnion epithelial cells. Cotreatment with IL1Ra reduced GBS-induced β-galactosidase activity and IL-6 and IL-8 secretion. Direct treatment with IL-1α or IL-1β confirmed the role of IL-1 signaling in the regulation of senescence in the fetal membrane. We further showed that GBS CD conditioned medium and IL-1 decreased cell proliferation in amnion epithelial cells. In summary, for the first time, we demonstrate GBS-induced senescence in the fetal membrane and present evidence of IL-1 pathway signaling between the choriodecidua and amnion layer of fetal membrane in a paracrine manner. Further studies will be warranted to understand the pathogenesis of adverse pregnancy outcomes associated with GBS infection and develop therapeutic interventions to mitigate these complications.
