Abstract
Fever during pregnancy can have detrimental effects for both the mother and foetus. However, during late pregnancy in mice, fever induced by the bacterial mimetic lipopolysaccharide (LPS) is suppressed while sickness symptoms like reduced food intake remain. This likely aims to safeguard the foetus from elevated temperatures around parturition. The mechanism mediating this maternal adaptation remains unknown. Prolactin and placental lactogen are high during late pregnancy, and the prolactin receptor (Prlr) is expressed by glutamatergic (Vglut2), and GABAergic (Vgat) neurons involved in fever. It is hypothesised that lactogenic hormone action on one of these populations in the brain mediates suppression of fever during late pregnancy.
To investigate this, the Prlr was knocked out from Vglut2 or Vgat neurons in mice (Vglut2KO & VgatKO). Pregnant knockout and control (Prlrlox/lox) mice were injected with saline on day 17 and LPS on day 18 of pregnancy with body temperature recorded using radiotelemetry. Deletion of Prlr from either of these populations did not prevent the suppression of the fever in late pregnancy, with no difference in the LPS response from controls (measured by area under the curve) (Vglut2KO: P = 0.3499, n = 8-9; VgatKO: P = 0.2167, n = 4-7 (two-way ANOVA)).
Furthermore, Vglut2KO and VgatKO mice displayed sickness symptoms, such as reduced food intake, (4.11 ± 0.21 g to 2.30 ± 0.21 g (presented as mean ± SEM) P = <0.0001, n = 9); (3.76 ± 0.19 g to 1.63 ± 0.17 g, P = <0.0001, n = 9) respectively (two-way ANOVA).
These data show that lactogenic hormone action on Vglut2 or Vgat neurons does not mediate late pregnancy fever suppression in mice. Ongoing work now aims to delete the Prlr from brain regions involved in fever to investigate if lactogenic action in those regions is required for late pregnancy fever suppression.