Role of exosomes in pregnancy loss (miscarriage) CD 9, 81, 63

Types of Evs:
Exosomes (less than 150 nm in diameter)
Microvesicles
Apoptotic bodies
Extracellular vesicles:
Secreted from different types of cells including blood cells, endothelial, trophoblast, cardiac and tumor cells.
Present in the blood circulation and other biological fluids under normal physiologic conditions
Level of EVs increase in a wide range of disease states

Contains RNA and proteins, that is secreted into the extracellular space by exocytosis when multivesicular bodies fuse with the plasma membrane
Consist of lipid bilayer

Alteration in translational activity
Angiogenesis
Proliferation
Metabolism,
Apoptosis
Exosomes can
regulate target cell activity via:
Functioning as a mechanism for intercellular communication.

Placenta secretes exosomes into maternal circulation and play important roles in several different aspects of pregnancy including feto- maternal signaling.
Size 40-120 nm
Released via exocytosis into maternal plasma
Contain many signaling molecules including proteins, mRNA, microRNA, and noncoding RNAs
Regulate target cell activity, angiogenesis, proliferation, metabolism, and apoptosis

Can be detected in maternal plasma from as early as 6 weeks of gestation
Number increases with advancing gestation
Increases in number in complicated pregnancies
Contain members of the chromosome 19 microRNA cluster
Placental exosome

Oocyte extracellular vesicles
Tetraspanin CD9 play an important role in gamete fusion
Oocytes transfer CD9 to the sperm head via “exosome-like” vesicles
CD9 associated EVs localized in perivitelline space of the oocyte
Expressed on the surface of the oocyte and surrounding somatic cells
Play role in a sperm-oocyte membrane fusion
Expression of CD9 and CD81 are predominantly localized in the Perivitelline space and zona pellucida respectively.
CD9 is primarily produced by the oocyte
CD81 is produced in the surrounding cumulus cells
doi: 10.1242/bio.20121420

Extracellular Vesicles are present and
secreted by the endometrium

The data suggest that the miRNA content of circulating exosomes in maternal blood might represent a biomolecular “fingerprint” of the progression of pregnancy.
Exosomal miRNAs in pre-term birth play role in cell-to-cell signaling and interaction, cellular growth and proliferation, and cellular development.

Pregnancy loss, also referred to as miscarriage or spontaneous abortion, is generally defined as a nonviable intrauterine pregnancy up to 20 weeks gestation.
Pregnancy loss
The major cause of SA is fetal chromosomal abnormalities, contributing to about 50-60% of the cases

Fetal cfDNA is produced
by the apoptosis of placental cells of the trophoblast.
Produced during normal pregnancies; however, the process of apoptosis is likely increased during complicated pregnancies, due to increased oxidative stress and inflammatory response
Noninvasive prenatal testing for chromosomal abnormalities can be performed using only a blood sample collected from the mother, which brings about new possibilities for prenatal diagnostics. Such a new technique is beneficial also when the increased concentrations of cell-free fetal DNA are detected in the circulation of mothers with various pregnancy complications

Take home message: