title: Lipopolysaccharide-induced maternal inflammation affects the gonadotropin-releasing hormone neuron development in fetal mice.
abstract: Recent studies provide evidence that prenatal immunological stress may affect the programming of reproductive health and sexual behavior in adult animals. The aim of this study was to investigate the influence of maternal inflammation, induced by an intraperitoneal (i.p.) injection of lipopolysaccharide (LPS, 45 µg/kg) on embryonic day 11.5 (E 11.5), on the development of the gonadotropin-releasing hormone (GnRH) system in mouse fetuses as well as on the proinflammatory cytokine level in pregnant mice and their fetuses. In the fetuses, the GnRH neuron migration from the olfactory pit to the forebrain was estimated on embryonic days 14.5 and 18.5. The levels of the proinflammatory cytokines interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, tumor necrosis factor (TNF)-α and leukemia inhibitory factor (LIF) were measured with the cytometric bead and ELISA array method in the maternal and fetal blood, amniotic fluid and fetal cerebrospinal fluid (CSF). According to our data, activation of the immune system by LPS treatment on embryonic day 11.5 leads to an increased quantity of neurons in the nasal and olfactory bulb areas and a decreased quantity in the forebrain area on embryonic day 14.5. There was a slight decrease in the total number of neurons in the forebrain area on embryonic day 18.5. The levels of proinflammatory cytokines were significantly increased within 3 h after LPS treatment in the maternal and fetal blood, amniotic fluid and fetal CSF. IL-6-receptor immunoreactivity was detected on olfactory/vomeronasal axons. Thus, prenatal immunological stress delays the GnRH neuron migration in the nasal compartment of mouse fetuses, which may be mediated by the regulation of IL-6, MCP-1 and LIF secretion in the maternal-fetal system.
authors.affiliation: Koltsov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Victoria S
authors.initials: VS
authors.lastname: Sharova
authors.forename: Marina S
authors.initials: MS
authors.lastname: Izvolskaia
authors.forename: Liudmila A
authors.initials: LA
authors.lastname: Zakharova
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D047109:Fetal Development; D005333:Fetus / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000502:physiology*; D011247:Pregnancy
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D007987:Gonadotropin-Releasing Hormone