Prenatal maternal vaginal inflammation increases anxiety and alters HPA axis signalling in adult male mice.

BACKGROUND: Maternal infection during pregnancy is known to adversely affect foetal development, but previous studies have rarely investigated the impact of gynaecological diseases during pregnancy on offspring during adulthood. Vaginitis is one of the most prevalent gynaecological diseases during pregnancy.

METHODS: The effect of maternal vaginal inflammation on offspring was simulated by inducing maternal vaginal infection. We performed a transvaginal injection of lipopolysaccharide (LPS) in pregnant mice to induce vaginitis and investigated their offspring by means of behavioural tests and molecular and cellular measurements.

RESULTS: Behavioural tests revealed that the offspring of mothers transvaginally injected with LPS exhibited sex-dependent differences. Male offspring showed increased anxiety-related behaviours, including reduced time exploring the open arm in the elevated plus maze test and light chamber in the light-dark box test. Serum levels of corticosterone were increased in LPS male offspring, indicating activation of the hypothalamic-pituitary-adrenal (HPA) axis. Corticotropin-releasing hormone (CRH) protein expression and c-Fos positive cells were increased in the hypothalamic paraventricular nucleus (PVN) in LPS male offspring, which presented with an increased number of microglia.

CONCLUSION: This study suggests that prenatal vaginal infection increases anxiety-like behaviour in male offspring, possibly via activation of the HPA axis.