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

Abstract

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.

The prenatal challenge with lipopolysaccharide and polyinosinic:polycytidylic acid disrupts CX3CL1-CX3CR1 and CD200-CD200R signalling in the brains of male rat offspring: a link to schizophrenia-like behaviours

“…Similar observations have been reported for the progeny of mouse dams injected with LPS at GD9 when challenged in adulthood [ 103 ]. Also, the offspring prenatally exposed to intrauterine inflammation [ 104 ] and vaginitis [ 105 ], which are both induced by LPS treatment, manifested anxiety-related behaviours. Additionally, in our study, the LPS-treated adult male rats did not display any changes in social interactions.…”

Maternal Immune Activation Sensitizes Male Offspring Rats to Lipopolysaccharide-Induced Microglial Deficits Involving the Dysfunction of CD200–CD200R and CX3CL1–CX3CR1 Systems

“…Consistent with our data, rats prenatally treated with LPS displayed more anxiety-like behaviours and enhanced stress responses [ 71 ]. Also, the offspring exposed to intrauterine inflammation [ 72 ] and vaginitis [ 73 ] before birth, which are both induced by LPS injection, manifested anxiety-related behaviours. Nevertheless, different species or strains, as well as diverse test conditions, exert crucial effects on the outcome of animal examinations of anxiety [ 74 ].…”

Effects of Prenatal Exposure to Inflammation Coupled With Stress Exposure During Adolescence on Cognition and Synaptic Protein Levels in Aged CD-1 Mice

“… Hernandez et al (2020) demonstrated that there are no significant differences between the sexes in age-related cognitive impairment (including spatial and working memory) in rats. Wang et al (2019) showed that prenatal exposure to inflammation leads to increased anxiety-related behavior in adult male offspring when compared with adult female offspring. Fernández de Cossío et al (2017) also reported a male-specific effect for intrauterine LPS exposure on synaptic pruning in the hippocampus of adult offspring, while the observed LPS-induced anxiety-related behavior deficits did not differ between the sexes.…”