TY - JOUR
T1 - Effects of miR-98 in intrauterine extracellular vesicles on maternal immune regulation during the peri-implantation period in cattle
AU - Nakamura, Keigo
AU - Kusama, Kazuya
AU - Ideta, Atsushi
AU - Kimura, Koji
AU - Hori, Masatoshi
AU - Imakawa, Kazuhiko
N1 - Funding Information:
This work was supported by Early-Career Scientists (18K14566 to K.K.) and Grant-in-Aid for Scientific Research (A) (16H02584 to K.I.) from Japan Society for the Promotion of Science. Computations were partially performed on the NIG supercomputer at ROIS National Institute of Genetics.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Evidence accumulated suggests that extracellular vesicles (EVs) present in uterine lumen play a role in conceptus-endometrial cell interactions during peri-implantation periods. However, how intrauterine EVs function on endometrium have not been well characterized. To study how intrauterine EVs affect endometrial milieu in cattle, bovine endometrial epithelial cells (EECs) were treated with EVs isolated from uterine flushing fluids (UFs) on day 17 or 20 pregnancy (P17, P20, respectively; conceptus implantation to endometrium begins on days 19–19.5). RNA extracted from EECs were then subjected to RNA sequence analysis. The analysis revealed that transcripts related to immune system were down-regulated in EECs treated with EVs on P20 compared with those on P17. To investigate whether microRNAs (miRNAs) in EVs regulate maternal immune system in the endometrium during the peri-implantation, microRNA sequence and in silico analyses were performed, identifying bta-miR-98 in EVs as a potential miRNA to regulate maternal immune system. Furthermore, the treatment of EECs with bta-miR-98 negatively regulated several immune system-related genes, CTSC, IL6, CASP4 and IKBKE, in EECs. These results suggest that EVs containing bta-miR-98 is a regulator of maternal immune system, possibly allowing the conceptus attachment to the endometrial epithelium during the peri-implantation period.
AB - Evidence accumulated suggests that extracellular vesicles (EVs) present in uterine lumen play a role in conceptus-endometrial cell interactions during peri-implantation periods. However, how intrauterine EVs function on endometrium have not been well characterized. To study how intrauterine EVs affect endometrial milieu in cattle, bovine endometrial epithelial cells (EECs) were treated with EVs isolated from uterine flushing fluids (UFs) on day 17 or 20 pregnancy (P17, P20, respectively; conceptus implantation to endometrium begins on days 19–19.5). RNA extracted from EECs were then subjected to RNA sequence analysis. The analysis revealed that transcripts related to immune system were down-regulated in EECs treated with EVs on P20 compared with those on P17. To investigate whether microRNAs (miRNAs) in EVs regulate maternal immune system in the endometrium during the peri-implantation, microRNA sequence and in silico analyses were performed, identifying bta-miR-98 in EVs as a potential miRNA to regulate maternal immune system. Furthermore, the treatment of EECs with bta-miR-98 negatively regulated several immune system-related genes, CTSC, IL6, CASP4 and IKBKE, in EECs. These results suggest that EVs containing bta-miR-98 is a regulator of maternal immune system, possibly allowing the conceptus attachment to the endometrial epithelium during the peri-implantation period.
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U2 - 10.1038/s41598-019-56879-w
DO - 10.1038/s41598-019-56879-w
M3 - Article
C2 - 31889113
AN - SCOPUS:85077158258
SN - 2045-2322
VL - 9
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 20330
ER -