Impact of prenatal cold stress on placental physiology, inflammatory response, and apoptosis in rats

Abstract

Prenatal cold stress is one of the earliest factors affecting mammalian health, and is associated with neonatal growth retardation and immune dysfunction, thus increasing disease susceptibility. The mechanisms underlying these observations remain unclear; hence, the objective of this study was to elucidate placental responses to cold stress. 60 maternal rats were randomly allocated to either stressed (n = 30) or non-stressed (control, n = 30) treatment conditions and 30 pubs (n=15) were used for the pups analysis. We found that maternal exposure to cold stress resulted in decreased body temperature, increased food intake without body weight gain, and a high level of plasma corticosterone (CORT) between gestational day (GD) 14 and GD21. In addition, gestation cold stress induced the placental expression of heat shock protein 70 (HSP70), IκBα, glucocorticoid receptor (GR), mineralocorticoid receptor (MR), 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2), interferon (IFN) regulatory factor 3 (IRF3), Caspase-3 proteins and altered the ratio of B-cell lymphoma-extra large (Bcl-xL) to Bcl-associated x (Bax) proteins on gestational GD15, GD17, GD19, and GD21, also resulted in the production of interleukin (IL)-1β. Next, gestational cold stress provoked a decrease in plasma GH levels of 21-day-old offspring, and the body weights of offspring were have no differences from postnatal day (PD) 1–21. Taken together, our results indicate that gestational cold stress induces placental apoptosis and the activation of NF-kB via HSP70/TLR4/NF-κB signaling pathways in the placenta, these changes may affect placental function and fetus development.

Intrauterine Microbiota: Missing, or the Missing Link?

“…In rodents, studies have shown that maternal stress during pregnancy is associated with an increase in pro-inflammatory cytokines such as IL-1β and IL-6 in the placenta [36,77,78]. Cold stress in pregnant rats resulted in an increase in IL-1β in the labyrinth [78]. In this study, placental samples per dam were of mixed sex, and accordingly conclusions about sex-specific effects were precluded.…”

“…The strong association between stress and inflammation has led to an increased interest in examining inflammatory markers in the intrauterine environment both in rodents and in humans. In rodents, studies have shown that maternal stress during pregnancy is associated with an increase in pro-inflammatory cytokines such as IL-1β and IL-6 in the placenta [36,77,78]. Cold stress in pregnant rats resulted in an increase in IL-1β in the labyrinth [78].…”

Prenatal exposure to particulate air pollution and gestational age at delivery in Massachusetts neonates 2001–2015

“…This is physiologically plausible based on evidence showing that extreme temperature (heat or cold stress) predisposed placenta at a higher risk of inflammation triggered by air pollutants. 51 , 52 …”

Gut health, stress, and immunity in neonatal dairy calves: the host side of host-pathogen interactions

“…However, research using rodent models suggests that prenatal cold stress can modulate the maternal hypothalamus-pituitary-adrenocortical (HPA) activity [ 40 ] responsible for releasing glucocorticoids, including cortisol, as well as altering maternal metabolism [ 41 ]. Interestingly, maternal cold stress can affect placental physiology [ 42 ]; therefore, it is conceivable that temperature is likely to affect intestinal development, similar to other maternal stressors such as undernutrition [ 43 ].…”