Bovine Extracellular Vesicles Change the Dynamics of Human Decidual Stromal Cells Decidualization

Decidualization of the endometrium is essential to healthy pregnancy. It is governed by a network of signals, including signalling via extracellular vesicles (EVs). Decidualization is often studied in cultured decidual stromal cells (DSC). However, a standard component of the culture medium in this model is bovine serum, which is abundant in EVs that can hypothetically interfere with the decidualization process. In this study we investigated the effect of depleting the medium of exogenous EVs. Human DSC were differentiated with progesterone, β-estradiol and cAMP in a regular and bovine EVs-removed medium for 10 days. Secreted prolactin, a decidualization marker, was assayed by Alinity method and prl transcription was analyzed via real-time qPCR. A disparity of DSC decidualization efficacy with and without bovine EVs under the same deciduogenic stimuli was revealed. A sustainable production of PRL (range: 96±16 mIU/L to 140±35 mIU/L) without bovine EVs contrasted to initial 2-fold higher PRL release and significant loss in the decidualization by day 10 with EVs. Prl gene expression remained the same in both conditions showing posttranslational regulation. Bovine serum EVs and factors dysregulate the quality of the long-term DSC response causing a collateral bias in the model of decidualization.