Expression of IkappaB Family in the Ovine Liver during Early Pregnancy

Abstract

During normal pregnancy, there is a dynamic regulation of the maternal immune system, including the liver, to accommodate the presence of the allogeneic foetus in the uterus. However, it was unclear that the expression of the IkappaB (IκB) family was regulated in the ovine maternal liver during early pregnancy. In this study, sheep livers were collected at day 16 of the oestrous cycle (NP16), and days 13, 16 and 25 of gestation (DP13, DP16 and DP25), and RT-qPCR, Western blot and immunohistochemistry analysis were used to analyse the expression of the IκB family, including B cell leukemia-3 (BCL-3), IκBα, IκBβ, IκBε, IKKγ, IκBNS and IκBζ. The results revealed that expression of BCL-3, IκBβ, IκBε and IKKγ peaked at DP16, and the expression of IκBα was increased during early pregnancy. In addition, the expression of IκBζ peaked at DP13 and DP16, and IκBNS peaked at DP13. IκBβ and IKKγ proteins were located in the endothelial cells of the proper hepatic arteries and portal veins, and hepatocytes. In conclusion, early pregnancy changed the expression of the IκB family, suggesting that the modulation of the IκB family may be related to the regulation of maternal hepatic functions, which may be favourable for pregnancy establishment in sheep.

Regulation of IkappaB Protein Expression by Early Gestation in the Thymus of Ewes

“…The study was carried out using Small-tail Han ewes of the same age (18 months) from September to December, and ewes were kept indoors with free access to feed and water. The experimental design was described previously [ 5 ]. Thymuses were collected after the females were euthanatized at days 13, 16, and 25 post-estrus for the pregnant ewes and on day 16 post-estrus for the nonpregnant ewes, as described previously [ 11 ].…”

“…Total RNA extraction and measurements of the concentration of total RNA were performed as described previously [ 5 ], and cDNA synthesis and specific primers synthesis were carried out as described previously [ 16 ]. Amplification was carried out as described previously [ 5 ]. The specific primers were synthesized by Shanghai Sangon Biotech Co., Ltd., Shanghai, China ( Table S1 ).…”

“…IFNT prevents conceptus rejection by the female by regulating the maternal innate immune system in ruminants [ 4 ]. Gene and protein expression levels of interferon-stimulated genes (ISGs), the progesterone receptor, and progesterone-induced blocking factor in the maternal immune organs were modulated by IFNT and progesterone during early pregnancy in the ovine [ 5 ].…”

“…NF-κB modulates maternal T-cell functions during normal pregnancy, and the dysregulation of NF-κB in the T-cell can be related to intrauterine growth restriction [ 7 ]. There is a modulation of NF-κB components in the maternal immune organs that play essential roles in ovine maternal immunoregulation and pregnancy maintenance [ 5 ]. Inhibitors of NF-κB (IκB) and IκB kinase (IKK) are the critical terminal components of NF-κB signaling, and IκB proteins include B cell leukemia-3 (BCL-3), IκBα (NFKBIA), IκBβ (NFKBIB), IκBε (NFKBIE), IKKγ (IKBKG), IκBNS (NFKBID) and IκBζ (NFKBIZ) [ 8 ].…”

“…The plasma IκBα level is downregulated in preeclamptic females compared with normotensive pregnant females; however, there is no significant difference in the plasma IκBα level between human immunodeficiency virus (HIV) positive and HIV-negative pregnant women [ 10 ]. Our previous studies reported that the expression of IκB proteins in ovine maternal liver, spleen, and lymph nodes was modulated during early pregnancy, which is associated with ovine maternal immune tolerance [ 5 , 11 ].…”