Late gestation heat stress induces inflammation and impacts nutrient transfer signature in the placenta of dairy cows

The conditions within the uterus where a mammalian fetus develops are crucial in shaping its physiological functions later in life. Changes in the availability of nutrients, oxygen, and hormones in the maternal blood stream can influence tissue development. We hypothesized that late gestation heat stress leads to alterations in gene expression in the cotyledonary tissue related to acute inflammation and impact the mechanisms of placental nutrient uptake, affecting the trajectory of fetal growth. Multiparous pregnant Holstein cows had lactation terminated (i.e. dried-off) at 232 ± 5 days of gestation and were randomly assigned to one of two treatments: cooling (CL; access to the shade of a barn plus forced ventilation via fans and water soakers over the feed lane to provide active evaporative cooling) or heat-stress (HT; access to the shade of a barn and natural ventilation, no active cooling) for the entire duration of their dry period. Maternal plasma (n = 28/trt) cortisol concentrations were measured at days −14, −7 prior to and at parturition. At delivery, placental cotyledonary tissue samples were collected and analyzed for gene expression (n = 4–5/trt). During the final weeks of gestation, treatment impacted plasma cortisol concentrations as calving approached (p = 0.04), wherein HT dams exhibited lower plasma cortisol concentrations than CL dams at −14 days (9.65 vs. 13.09 ± 1.5 ng/ml; p < 0.001) and at parturition (16.97 vs. 22.32 ± 1.4 ng/ml; p < 0.001), combined with significant changes in placental gene pathways associated with acute inflammation and cortisol synthesis and secretion. Specifically, pathways related to interleukin-6 (IL6) and NLR family pyrin domain-containing protein 3 (NLRP3), which regulate inflammation, were upregulated by HT, suggesting placental inflammation. Additionally, pathways involved in nutrient transfer and amino acid metabolism were impaired, as HT downregulated key genes responsible for these functions, especially serine biosynthesis. These findings indicate that HT during late gestation leads to dysregulation of cortisol secretion pattern in maternal plasma, resulting in reduced cortisol levels in the HT animals. Additionally, it also caused placental inflammation impacting feto-maternal transfers, highlighting the importance of late gestation period on fetal development and managing maternal environmental stressors in dairy production.