Abstract
Fever during pregnancy increases the risk of complications for both the foetus and mother. However, during late pregnancy in mice, fever induced by the bacterial mimetic lipopolysaccharide (LPS) is suppressed while other sickness symptoms like reduced food intake remain. This likely plays a role in safeguarding the foetus from elevated temperatures around parturition. What mediates this mechanism is unknown. Prolactin and placental lactogen are high during late pregnancy, and there is expression of the prolactin receptor (Prlr) in glutamatergic (Vglut2) neuronal populations involved in fever. It is hypothesised that lactogenic hormone action on glutamatergic neuronal populations in the brain mediates suppression of fever responses during late pregnancy.
To investigate this hypothesis, the Prlr was specifically knocked out from glutamatergic neurons (Prlrlox/lox/Vglut2Cre). Pregnant mice were injected with saline on day 17 and LPS on day 18 of pregnancy with body temperature recorded using radiotelemetry. Inconsistent with the hypothesis, deletion of Prlr from glutamatergic neurons did not prevent the suppression of the fever response in late pregnancy, as there was no difference in the LPS response from controls (Prlrlox/lox) (measured by area under the curve) (one-way ANOVA, P = 0.7537, n = 6-7).
Despite the absence of a fever response, sickness symptoms, such as reduced food intake, were observed in both Prlrlox/lox/Vglut2Cre (4.18 ± 0.31 g to 2.42 ± 0.27 g (presented as mean ± SEM) (one-way ANOVA, P = 0.0023, n = 6)), and Prlrlox/lox mice (3.64 ± 0.17 g to 2.28 ± 0.21 g, one-way ANOVA, P = 0.0019, n = 8).
These data show that lactogenic hormone action on Vglut2 neurons does not mediate late pregnancy fever suppression in mice. This study begins to shed light on the mechanism by which fever responses are suppressed.