The early stage of pregnancy modulates toll-like receptor signaling in the ovine liver

Abstract

Toll-like receptors (TLRs) participate in maternal immune regulation at multiple maternal-fetal interfaces. The liver is crucial for innate and adaptive immunity during pregnancy. The objective of this study was to measure the expression of genes and proteins related to TLR signaling. In this study, livers were obtained from ewes on day 16 of the estrous cycle, and on days 13, 16 and 25 of gestation, and RT-qPCR, western blot and immunohistochemistry were employed to measure the expression of genes and proteins related to TLR signaling, including TLR2, TLR3, TLR4, TLR5, TLR7, TLR9, myeloid differentiation primary-response protein 88 (MyD88), tumor necrosis factor receptor associated factor 6 (TRAF6) and interleukin-1receptor-associated kinase 1 (IRAK1). Our data showed that the expression levels of TLR2, TLR3, TLR5, TLR9 and TRAF6 were increased, but those of TLR4 and TLR7 were decreased in the liver during early pregnancy. In addition, the expression levels of MyD88 and IRAK1 were the highest on days 13 and 16 of pregnancy, respectively, and the MyD88 protein was located in endothelial cells of proper hepatic arteries and portal veins and in hepatocytes. In conclusion, early pregnancy modulates TLR signaling in the maternal liver in sheep, which may participate in maternal immune regulation.

Expression of IkappaB Family in the Ovine Liver during Early Pregnancy

“…Tissue sections were photographed using a light microscope (Nikon Eclipse E800, Tokyo, Japan) with a digital camera (AxioCam ERc 5s), and the intensity of staining was analysed through the photos by two investigators in a blinded fashion. The intensity of staining was scored on a scale of 0 to 3:0, no staining; 1, weak staining; 2, strong staining; 3, stronger staining, as described previously [ 24 ].…”

“…It has been reported that in the ovine maternal liver, early pregnancy regulates the expression of gonadotropin releasing hormone and prolactin, and their receptors, prostaglandin synthases, T helper (Th) cytokines, melatonin receptor 1, CD4, [ 19 , 20 , 21 , 22 , 23 ]. Furthermore, toll-like receptor pathway, nuclear factor kappa B (NF-κB) pathway and complement pathway are modulated in the ovine maternal liver during early pregnancy [ 24 , 25 , 26 ].…”

Expression of nuclear factor kappa B components in the ovine maternal liver in early pregnancy periods

“…Our previous studies indicate that early pregnancy has effects on the expression of P4 receptor (PGR), P4‐induced blocking factor (Zhang et al, 2019), prostaglandin (PG) synthases (Yang, Han, et al, 2020), ISGs (Yang, Li, et al, 2020), and T helper cytokines (Yang, Bai, et al, 2019) in maternal livers of ewes. In addition, there are variations in the expression of melatonin receptor 1, CD4, Toll‐like receptors, complement components, gonadotropin releasing hormone (GnRH), and GnRH receptor in the maternal liver during early pregnancy in sheep (Bai et al, 2020; Cao et al, 2021; Feng et al, 2021; Gao et al, 2021). Nuclear factor kappa B (NF‐κB) is a heterodimeric transcriptional regulator, expressed in all cell types, and NF‐κB signaling participates in the maintenance of liver homoeostasis (Robinson & Mann, 2010).…”