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Uterine fluid tells fetus about mom's world
A developing fetus bathes in a mixture of cellular secretions and proteins unique to its mother's uterus. Before fertilization, the pH of uterine fluid helps create a conducive environment for sperm migration, and afterward, its volume supports the embryo as it implants onto the wall of the uterus.
A review of this research appears on June 22 in Trends in Molecular Medicine.
Studies in livestock, rodents, and humans have shown that information from a mother's environment (e.g., food availability, stress, and pollutant exposure) can leave epigenetic tags on the DNA of her fetus, potentially influencing the progression and long-term health of the developing embryo.
Scientists have hypothesized that blood flow via the placenta might constitute one way the body communicates the mother's condition to the fetus. Yet, there is evidence the fetus reacts to changes such as the mother's diet, long before the establishment of the placenta.
"This suggests the involvement of uterine fluid as the communication medium to transfer information between the maternal environment and the floating embryo.
While there is much to be learned about how mother-fetus communication takes place, the theory is that information in extracellular vesicles (molecular packages that move from cell to cell) within uterine fluid and tissue deliver their cargo, including microRNAs and amino acids, to the fetus. These molecules may be tagging fetal cell DNA in ways that alter which genes are being expressed, and thus can contribute to "programming" how the embryo and/or placenta develop. Consequently, researchers are interested in learning which specific maternal environmental exposures and/or behaviors could change the composition of molecules transported via the uterine fluid to the fetus.
For example, mouse studies have shown that a low-protein maternal diet can reduce the level of certain amino acids in uterine fluid and affect gene expression of nutrition- transport-related genes. While these changes might prevent malnutrition in the developing embryo, once grown, the mouse offspring are more predisposed to heart disease when compared to animals on a regular diet.
Hongmei Wang co-senior author of this paper, speculates that uterine fluid could someday be used to analyze or even manipulate what signals are being received by a fetus.
"For now, uterine fluid collection is not a standard biomarker, yet many studies have revealed its potential role for non-invasive analysis."
"One, it can be screened by using ultrasound coupled with computational and biomechanical analysis; two, uterine fluid can easily be collected during endometrial examination."
Hongmei Wang PhD, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China and co-senior author of the paper.
Once considered a simple medium for sperm and embryo transport, the functional spectrum of uterine fluid is now expanding. Novel molecular players, such as extracellular vesicles and mobile RNAs, have been detected in the uterine fluid of livestock, rodents, and humans. These novel molecules, together with previously known ions and proteins, ensure uterine fluid homeostasis and facilitate embryo–maternal interactions. Here, we propose that these molecules may also carry information that mirrors maternal environmental exposure and possibly relay such information to the embryo via uterine fluid, generating long-term epigenetic effects on the offspring via embryonic and placental programming. Moreover, the development of systematic profiling of uterine fluid molecular signatures may now hold promise, relying on high-throughput methods and non-invasive biomarkers for clinical use.
This work is supported by the National Basic Research Program of China, the Ministry of Science and Technology of China, the National Natural Science Foundation of China, the National Key Research and Development Program of China, and the Youth Innovation Promotion Association, CAS.
Trends in Molecular Medicine (@TrendsMolecMed), published by Cell Press, is a monthly review journal that facilitates communication between groups of highly trained professionals who share the common goal of understanding and explaining the molecular basis of disease as it relates to new clinical practice. Visit: http://www.cell.com/trends/molecular-medicine. To receive Cell Press media alerts, please contact email@example.com.
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Normal uterine fluid environment during embryo preimplantation.
Image Credit: Zhang, Ying et al., Trends in Molecular Medicine 2017