The results of their research point to the key role of extracellular vesicles, unique molecular cargo carriers secreted by both the embryo and the mother.

The mechanisms that determine the proper maintenance of pregnancy in various species of mammals and the process of communication between the embryo and the mother (how it takes place and with what factors) are the topics of the scientific interests of Professor Monika Kaczmarek, who heads the Molecular Biology Laboratory at the Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences in Olsztyn.

In early pregnancy, when the embryo reaches the uterus, intensive communication begins between the embryo and the uterus. The exchange of signals is one of the factors that determine the successful implantation (nesting) of the embryo in the uterine wall. Professor Monika Kaczmarek explains the course of this dialogue: 'The embryo sends the signal: +I am here+ and the uterus +responds+ with a readiness to accept the embryo and provide the factors and nutrients necessary for its further development. It is known that hundreds of particles are involved in this dialogue, but despite the identification of many of them, the full understanding of the complexity of this mechanism still remains a mystery,’ says Professor Kaczmarek.

The scientist adds that understanding the communication process between the embryo and the mother will allow researchers to answer questions about the causes of pregnancy failure, which may depend, for example, on genetic defects of the embryo, lack of readiness of the uterus to accept the embryo (i.e. uterine receptivity) or disorders of the dialogue.

Research conducted by Professor Kaczmarek's team has shown that the early stages of embryo implantation are regulated by the exchange of extracellular follicles between the embryo and the endometrium (the mucous membrane lining the uterine cavity). 'Extracellular vesicles (EVS) are nanoparticles covered with a membrane, secreted by all types of cells in living organisms. Recently, they have gained recognition as an important element of intercellular communication. What's more, over the past decade, their role has become particularly important in the area of mammal reproduction biology, attracting the attention of many scientific teams and researchers around the world,’ says Kaczmarek. 

The researchers used a domestic animal model (Sus scrofa) with an extended preimplantation period, which facilitates investigating the dialogue between the embryo and the mother. Scientists isolated extracellular vesicles from uterine fluid taken in various days of pregnancy, and then confirmed their participation in maintaining this key communication.

'We have shown that during early pregnancy, the uterine lumen is abundant with extracellular vesicles that carry a plethora of miRNAs able to target the expression (a process, during which specific genetic information is decoded and transferred to +protein production+) of genes involved in embryonic and organismal development,' says Professor Kaczmarek. She adds that upon the delivery to primary trophoblast cells, these extracellular vesicles affect genes governing development as well as cell-to-cell signaling and interactions, consequently having an impact on trophoblast cell proliferation (cell ability to multiply), migration, and invasion.

Based on this, the scientists conclude that the exchange of a unique population of extracellular vesicles and their molecular cargo at the maternal-embryo interface is the key to the success of embryo implantation and pregnancy.

The research results were published in The FASEB Journal and constitute an important part of Dr. Joanna Szuszkiewicz's doctoral dissertation.

Extracellular vesicles are also the subject of further scientific publications by the team of researchers from the Institute of Animal Reproduction and Food Research PAS in Olsztyn, which have just appeared in Cell Communication and Signaling and The FASEB Journal. They are part of Maria Guzewskas' doctoral dissertation.

'We have shown that the synthesis of extracellular vesicles in the uterus depends on embryonic signals. Moreover, we have shown that miRNA present in the embryo's cells regulates the expression of genes that determine the formation of a specific population of EVs secreted by the embryo. This breakthrough discovery indicates the key role of the embryo and its signals in defining subsequent stages of pregnancy with the participation of extracellular vesicles,’ says Professor Kaczmarek. (PAP)

author: Agnieszka Libudzka

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