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Prenatal Programming of Neuroendocrine System Development by Lipopolysaccharide: Long-Term Effects
Marina Izvolskaia1, Viktoria Sharova2, Liudmila Zakharova3
1Koltsov Institute of Developmental Biology, Russian Academy of Sciences, 119334 Moscow, Russia. izvolskaya@hotmail.com.
International Journal of Molecular Sciences
|November 25, 2018
Summary
Maternal exposure to lipopolysaccharide (LPS) during pregnancy disrupts fetal development, impacting neuroendocrine and reproductive systems. Epigenetic mechanisms offer potential for correcting these developmental defects.
Area of Science:
- Reproductive biology
- Developmental neuroscience
- Immunology
Background:
- Maternal stress during fetal development can alter epigenetic mechanisms, affecting physiological systems.
- Lipopolysaccharide (LPS) exposure simulates bacterial infection, acting as a potent inflammatory factor that programs fetal development.
- LPS-induced cytokine changes can impact brain development, behavior, and neuroendocrine functions, with potential links to anxiety, depression, and neurodegenerative diseases.
Purpose of the Study:
- To investigate the effects of LPS-induced maternal immune stress on fetal development.
- To examine the molecular mechanisms underlying LPS-induced disruptions in neuroendocrine and reproductive systems.
- To explore the role of epigenetic mechanisms in mediating these developmental effects.
Main Methods:
- Experimental simulation of maternal immune stress using lipopolysaccharide (LPS) in pregnant rats.
- Measurement of pro- and anti-inflammatory cytokine levels (IL-6, TNFα, LIF, MCP-1) in maternal and fetal systems.
- Assessment of gonadotropin-releasing hormone (GnRH) production and reproductive system development.
Main Results:
- LPS exposure increased maternal and fetal levels of IL-6, LIF, and MCP-1.
- These cytokine changes were associated with disturbed development and function of GnRH production.
- The study identified disruptions in reproductive system development due to maternal LPS exposure.
Conclusions:
- Maternal immune stress during early pregnancy, simulated by LPS, significantly impacts fetal neuroendocrine and reproductive system development.
- Elevated inflammatory cytokines play a crucial role in mediating these adverse developmental effects.
- Epigenetic mechanisms are highly responsive to developmental factors, presenting opportunities for therapeutic interventions to correct defects.
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