Abstract
An understanding gene-gene interaction helps users to design the next experiments efficiently and (if applicable) to make a better decision of drugs application based on the different biological conditions of the patients. This study aimed to identify changes in the hidden relationships between pro- and anti-inflammatory cytokine genes in the bovine oviduct epithelial cells (BOECs) under various experimental conditions using a multilayer response surface method. It was noted that under physiological conditions (BOECs with sperm or sex hormones, such as ovarian sex steroids and LH), the mRNA expressions of IL10, IL1B, TNFA, TLR4, and TNFA were associated with IL1B, TNFA, TLR4, IL4, and IL10, respectively. Under pathophysiological + physiological conditions (BOECs with lipopolysaccharide + hormones, alpha-1-acid glycoprotein + hormones, zearalenone + hormones, or urea + hormones), the relationship among genes was changed. For example, the expression of IL10 and TNFA was associated with (IL1B, TNFA, or IL4) and TLR4 expression, respectively. Furthermore, under physiological conditions, the co-expression of IL10 + TNFA, TLR4 + IL4, TNFA + IL4, TNFA + IL4, or IL10 + IL1B and under pathophysiological + physiological conditions, the co-expression of IL10 + IL4, IL4 + IL10, TNFA + IL10, TNFA + TLR4, or IL10 + IL1B were associated with IL1B, TNFA, TLR4, IL10, or IL4 expression, respectively. Collectively, the relationships between pro- and anti-inflammatory cytokine genes can be changed with respect to the presence/absence of toxins, sex hormones, sperm, and co-expression of other gene pairs in BOECs, suggesting that considerable cautions are needed in interpreting the results obtained from such narrowly focused in vitro studies.
Highlights
The epithelial tissue of the female reproductive tract (FRT) reacts to different stimuli, such as pathogens, hormones, allogeneic sperm, semi-allogeneic embryo, and biochemical stressors; it secretes immune-related factors such as pro- and anti-inflammatory cytokines[1,2,3,4] which are involved in the physiological or pathophysiological control of the oviduct function
We defined three scenarios for the hidden layer of the multi-layer response surface method (MLRSM) based on the number of the input dataset as scenario 1, scenario 2 (the mRNA expression dataset of two genes was used as the input dataset for predicting the target gene, Figs 1b,d and 2a), and scenario 3
Using the mRNA expression data of all genes, the analysis showed that compared to the multiple-linear regression (MLR), response surface method (RSM), MLRSM and MLRSM, the scenario 2 of the MLRSM model reduced the root-mean-square errors (RMSE) by 50.1%, 46.2%, 39.7%, and 21.8% and the mean bias error (MBE) by 67.3%, 72.7%, 57.7%, and 41.6%, respectively (Table 1)
Summary
The epithelial tissue of the female reproductive tract (FRT) reacts to different stimuli, such as pathogens, hormones, allogeneic sperm, semi-allogeneic embryo, and biochemical stressors; it secretes immune-related factors such as pro- and anti-inflammatory cytokines[1,2,3,4] which are involved in the physiological or pathophysiological control of the oviduct function. Kowsar et al.[11] and Fahey et al.[1] reported that ovarian sex steroids inhibited LPS-induced expression of the pro-inflammatory mediators in BOECs and human uterine epithelial cells. These immune responses became more complicated when it was reported that a low dose of LPS (10 ng/mL) induced a pro-inflammatory response whereas high-dose LPS (100 ng/mL) favored an anti-inflammatory response in BOECs11. These findings reveal a complex regulation of the mRNA expression of pro- and anti-inflammatory cytokine genes based on the different experimental/biological conditions of the oviduct epithelium. This may give a better understanding of the immunological responses in BOECs under various biological or experimental conditions
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
