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Visualizing The Placenta, a Critical but Poorly Understood Organ

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Ultrasound image of placenta
Ultrasound images showing fetal (left) and maternal (right) placental vasculature. Credit: Eastern Virginia Medical School and University of Texas Medical Branch

The placenta is the Rodney Dangerfield of organs; it gets no respect, no respect at all. This short-lived but critical organ supports pregnancy by bringing nutrients and oxygen to the fetus, removing waste, providing immune protection, and producing hormones to support fetal development.

It also influences the lifelong health of both mother and child. Problems with the placenta can lead to preeclampsia, gestational diabetes, poor fetal growth, preterm birth, and stillbirth. Although we were all connected to one, the placenta is the least understood, and least studied, of all human organs.

What we do know about the human placenta largely comes from studying it after delivery. But that’s like studying the heart after it’s stopped beating. It doesn’t help us predict complications in time to avert a crisis.

To fill these knowledge gaps, NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) developed the Human Placenta Project (HPP) to noninvasively study the placenta during pregnancy. Since 2014, this approximately $88 million collaborative research effort has been developing ultrasound, magnetic resonance imaging (MRI), and blood-based biomarker methods to study how the placenta functions in real time and in greater detail.

As illustrated in the image above, advanced ultrasound tools allowed HPP researchers at Eastern Virginia Medical School, Norfolk, and the University of Texas Medical Branch, Galveston, to gain a detailed look at the placenta’s intricate arrangement of blood vessels, or vasculature. By evaluating both fetal (left panel) and maternal (right panel) placental vasculature in 610 pregnant people starting at 13 weeks of gestation, the investigators aimed to identify early changes that predicted later complications.

They observed that such changes can start in the first trimester and affect both the vasculature and placental tissue. While further research is needed, these findings suggest that placental ultrasound monitoring can inform efforts to prevent and treat pregnancy complications.

Another HPP team led by Boston Children’s Hospital is developing an MRI strategy to monitor blood flow and oxygen transport through the placenta during pregnancy. Interpreting and visualizing MRI data of the placenta is challenging because of its variable shape, the tendency of muscles in the uterus to begin tightening or contracting well before labor [1], and other factors.

As shown in the video above, the researchers developed a way to account for the motion of the uterus and “freeze” the placenta to make it easier to study (left two panels of video) [2]. They also developed algorithms to better visualize the complex patterns of placental oxygen content during contractions (center panel) [3]. The scientists then carried out initial visualizations of blood flow through the placenta shortly after delivery (second panel from right) [4].

They now intend to map these MRI findings to the placenta itself after delivery (far right panel), which will allow them to explore how additional factors such as gene expression patterns and genetic variants contribute to placental function. Ultimately, they plan to apply these MRI techniques to monitor the placenta in real time during pregnancy and identify changes that indicate compromised function early enough to adjust maternal management as needed.

Other HPP efforts focus on identifying components in maternal blood that reflect the status of the placenta. For example, an HPP research team led by scientists at the University of California, Los Angeles, adapted non-invasive prenatal testing methods to analyze genetic material shed from the placenta into the maternal bloodstream. Their findings suggest that distinctive patterns in this genetic material detected early in pregnancy may indicate risk for later complications [5].

Another HPP team, led by investigators at Columbia University, New York, helped establish that extracellular RNAs (exRNAs) released by the placenta into maternal circulation reflect the placenta’s status at a cellular level beginning in the first trimester. To harness the potential of exRNA biomarkers, the investigators are optimizing methods to isolate, sequence, and analyze exRNAs in maternal blood.

These are just a few examples of the cutting-edge work being funded through the HPP, which complements NICHD’s longstanding investment in basic research to unravel the physiology of and real-time gene expression in the placenta. Unlocking the secrets of the placenta may one day help us to prevent and treat a range of common pregnancy complications, while also providing insights into other areas of science and medicine such as cardiovascular disease and aging. NICHD is committed to giving this important organ the respect it deserves.

References:

[1] Placental MRI: Effect of maternal position and uterine contractions on placental BOLD MRI measurements. Abaci Turk E, Abulnaga SM, Luo J, Stout JN, Feldman H, Turk A, Gagoski B, Wald LL, Adalsteinsson E, Roberts DJ, Bibbo C, Robinson JN, Golland P, Grant PE, Barth, Jr WH. Placenta. 2020 Jun 1; 95: 69-77.

[2] Spatiotemporal alignment of in utero BOLD-MRI series. Turk EA, Luo J, Gagoski B, Pascau J, Bibbo C, Robinson JN, Grant PE, Adalsteinsson E, Golland P, Malpica N. J Magn Reson Imaging. 2017 Aug;46(2):403-412.

[3] Volumetric parameterization of the placenta to a flattened template. Abulnaga SM, Turk EA, Bessmeltsev M, Grant PE, Solomon J, Golland P. IEEE transactions on medical imaging. 2022 April;41(4):925-936.

[4] Placental MRI: development of an MRI compatible ex vivo system for whole placenta dual perfusion. Stout JN, Rouhani S, Turk EA, Ha CG, Luo J, Rich K, Wald LL, Adalsteinsson E, Barth, Jr WH, Grant PE, Roberts DJ. Placenta. 2020 Nov 1; 101: 4-12.

[5] Cell-free DNA methylation and transcriptomic signature prediction of pregnancies with adverse outcomes. Del Vecchio G, Li Q, Li W, Thamotharan S, Tosevska A, Morselli M, Sung K, Janzen C, Zhou X, Pellegrini M, Devaskar SU. Epigenetics. 2021 Jun;16(6):642-661. 

Links:

Human Placenta Project (Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH)

Preeclampsia (NICHD)

Understanding Gestational Diabetes (NICHD)

Preterm Labor and Birth (NICHD)

Stillbirth (NICHD)

Abuhamad Project Information (NIH RePORTER)

Grant Project Information (NIH RePORTER)

Devaskar Project Information (NIH RePORTER)

Williams Project Information (NIH RePORTER)

Note: Acting NIH Director Lawrence Tabak has asked the heads of NIH’s Institutes and Centers (ICs) to contribute occasional guest posts to the blog to highlight some of the interesting science that they support and conduct. This is the 10th in the series of NIH IC guest posts that will run until a new permanent NIH director is in place.

4 Comments

  • Nathan says:

    How about ectopic pregnancies that are caught late? What sort of rudimentary placenta is in place there to allow fetal development beyond the blastocyst state? In doing transgenic or knockout animals, similar to IVF, most of the implantations are at the blastocyst/trophoblast state before neurogenesis. And is there any genetics pertaining to ciliary dysfunction that can cause an increase in ectopic pregnancies? Seems something worthy of a RO1 in terms of “orphan indications”.

  • Lydia says:

    Given the aspect of fetal viability outside the uterus, what is the earliest known viable life without modern medical intervention in a NICU? Since the environment of proper fetal development dictates if there are problems later in life that may be something of interests as well …

  • Victor says:

    Great summary of recent research on placental function. It is really needed. In our FAES Physiology class, the placenta was voted the most amazing organ in the body. It beat the brain!

  • Fahmida P. says:

    Most of the woman in the world are suffering placenta based complications during their pregnancy. Give higher importance for the placenta in your research.

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