Disruption of Intranasal GnRH Neuronal Migration Route into the Brain Induced by Proinflammatory Cytokine IL-6: Ex Vivo and In Vivo Rodent Models

Int J Mol Sci. 2023 Nov 5;24(21):15983. doi: 10.3390/ijms242115983.

Abstract

Maternal immune activation results in altered levels of cytokines in the maternal-fetal system, which has a negative impact on fetal development, including the gonadotropin-releasing hormone (GnRH) system, which is crucial for the reproduction. Suppression of GnRH-neuron migration may be associated with cytokine imbalances, and primarily with proinflammatory cytokine interleukin (IL)-6. This study aimed to determine the effects of IL-6 and monoclonal antibody to IL-6 or IL-6R or polyclonal IgG on the formation of migration route of GnRH-neurons in ex vivo and in vivo rodent models on day 11.5 of embryonic development. The increased level of IL-6 in mouse nasal explants suppressed peripherin-positive fiber outgrowth, while this led to an increase in the number of GnRH-neurons in the nose and olfactory bulbs and a decrease in their number in the fetal brain. This effect is likely to be realized via IL-6 receptors along the olfactory nerves. The suppressive effect of IL-6 was diminished by monoclonal antibodies to IL-6 or its receptors and by IgG.

Keywords: GnRH neuron migration; IL-6; IL-6mAbs; IL-6mRAbs; IgG modulation; LPS; mouse fetus; olfactory placodes.

MeSH terms

  • Animals
  • Brain / metabolism
  • Cell Movement
  • Cytokines* / pharmacology
  • Female
  • Gonadotropin-Releasing Hormone* / metabolism
  • Immunoglobulin G / pharmacology
  • Interleukin-6 / pharmacology
  • Mice
  • Pregnancy
  • Rodentia / metabolism

Substances

  • Cytokines
  • Gonadotropin-Releasing Hormone
  • Immunoglobulin G
  • Interleukin-6
  • interleukin-6, mouse