Changes in Oviductal Cells and Small Extracellular Vesicles miRNAs in Pregnant Cows

Abstract

Early embryonic development occurs in the oviduct, where an ideal microenvironment is provided by the epithelial cells and by the oviductal fluid produced by these cells. The oviductal fluid contains small extracellular vesicles (sEVs), which through their contents, including microRNAs (miRNAs), can ensure proper cell communication between the mother and the embryo. However, little is known about the modulation of miRNAs within oviductal epithelial cells (OECs) and sEVs from the oviductal fluid in pregnant cows. In this study, we evaluate the miRNAs profile in sEVs from the oviductal flushing (OF-sEVs) and OECs from pregnant cows compared to non-pregnant, at 120 h after ovulation induction. In OF-sEVs, eight miRNAs (bta-miR-126-5p, bta-miR-129, bta-miR-140, bta-miR-188, bta-miR-219, bta-miR-345-3p, bta-miR-4523, and bta-miR-760-3p) were up-regulated in pregnant and one miRNA (bta-miR-331-5p) was up-regulated in non-pregnant cows. In OECs, six miRNAs (bta-miR-133b, bta-miR-205, bta-miR-584, bta-miR-551a, bta-miR-1193, and bta-miR-1225-3p) were up-regulated in non-pregnant and none was up-regulated in pregnant cows. Our results suggest that embryonic maternal communication mediated by sEVs initiates in the oviduct, and the passage of gametes and the embryo presence modulate miRNAs contents of sEVs and OECs. Furthermore, we demonstrated the transcriptional levels modulation of selected genes in OECs in pregnant cows. Therefore, the embryonic-maternal crosstalk potentially begins during early embryonic development in the oviduct through the modulation of miRNAs in OECs and sEVs in pregnant cows.

Characterization and profiling analysis of bovine oviduct and uterine extracellular vesicles and their miRNA cargo through the estrous cycle

“…These changes occurring in the oviduct during the pre‐ovulatory period (stage 4) may be involved in preparing the oviduct to receive gametes/early embryo, while for the uterus, the post‐estrous period (stage 3), coincides with embryo/conceptus development, reception, and implantation period, and regulates the expression of prostaglandin‐endoperoxide implantation. In agreement with this, a recent study confirms that miRNAs of the OF‐EVs modulate the early embryonic development in the oviduct in pregnant cows 58 . In mice uterus, upregulation of miR‐101a and miR‐199a at the site of embryo implantation, thereby preventing unnecessary growth elsewhere in the uterus 59 .…”

“…In agreement with this, a recent study confirms that miRNAs of the OF-EVs modulate the early embryonic development in the oviduct in pregnant cows. 58 In mice uterus, upregulation of miR-101a and miR-199a at the site of embryo implantation, thereby preventing unnecessary growth elsewhere in the uterus. 59 Although these two miRNAs were not upregulated in UF-EVs in this study, they were expressed among the most common UF-EV miRNA across the estrous cycle.…”

An interactive analysis of the mouse oviductal miRNA profiles

“…Moreover, microRNAs are emerging as regulators of different physiological and pathological processes in fertilization and embryo development ( Hossain et al, 2012 ; Gross et al, 2017 ; Tesfaye et al, 2018 ; Salilew-Wondim et al, 2020 ). Interestingly, they have been discovered also in the oviductal fluid ( Almiñana et al, 2018 ; Fereshteh et al, 2018 ; Gonella-Diaza et al, 2021 ; Mazzarella et al, 2021 ), packaged within the extracellular vesicles (EVs, also called oviductosomes, OVS) ( Gross et al, 2017 ; Fereshteh et al, 2018 ) that might act as natural nanoshuttles, bringing key components (lipids, proteins, RNA molecules and miRNAs) from the oviduct to the gametes or the embryos ( Almiñana et al, 2018 ). As a result, the OVS may encapsulate miRNAs, preventing degradation and increasing their stability in OF.…”

The Complicated Effects of Extracellular Vesicles and Their Cargos on Embryo Implantation

“…Early embryonic development occurs in the oviduct, where an ideal microenvironment is provided by epithelial cells and by the oviductal fluid produced by these cells (56). OEVs are emerging as key players in the embryo-maternal interactions (37).…”