Two interesting research projects in the field of embryology made headlines recently. Because they are somewhat connected I will grab them together. As a closure, I will share some thoughts on a gadget that was recently launched and that allows women to hear, record and share their unborn baby’s heartbeat. So if you’re a scientist or a future parent and you don’t want to miss out on a heartbeat you better read on.
The first research project lies at the core of our existence as it focusses on the first organ that develops during pregnancy: our heart! In our embryology classes, we are all taught that the first human heartbeat occurs at day 21 after conception. These researchers however, suggest that it is more likely that the heart starts beating five days earlier, at 16 days after conception.
Their discovery came to light after fluorescent markers had been linked to calcium molecules in the embryo of a mouse. This allowed the research team to pinpoint at which stage of development the calcium triggers the muscle cells of the heart to contract and increase in coordination, which ultimately results in a heartbeat. A protein named NCX1 turned out to be heavily involved in facilitating the calcium signals. The team was able to identify the key molecules in this process and to distinguish the earliest stages leading to a beating heart. The first heartbeat is crucial for the further development of the embryo because it supplies oxygen and nutrients and has as such also an impact on its own development.
Why is this new discovery relevant? In the UK, approximately 12 babies a day (one in every 180 babies, 4000 each year) are born with congenital heart diseases. These heart defects originate in the womb. Enlarging our body of knowledge on the development of the human heart and unravelling its secrets might be key in preventing fetal heart conditions and in the further development of stem cells into cardiac cells to cure adult heart conditions. However, some remarks can be made, and this brings us to the second research project.
3D Embryo Atlas
A research team in the Netherlands has launched an interactive 3D embryo atlas that unveils the human embryologic development during the first two months of development (that is, seventeen different stages in the first eight weeks) in astounding detail. The digital models are based on the Carnegie Collection of embryos. This is a huge collection of digital photographs of stained sections of tissues of embryos, collected during hysterectomies over the last 60-100 years.
It took a lot of manual work by the 75 students involved in the project to construct the 3D digital models: lines had to be drawn around sections, organs and tissues of more than 1000 sections up to 150 organs and structures had to be identified. Their work was not in vain, as it has already generated important new insights. According to Bernadette de Bakker (University of Amsterdam), co-leader of the project, one of them is that there turn out to be differences in the development of some organs between the human embryo and chick or mouse embryos: some structures develop earlier while others develop later. This new finding can have implications for previous research in which mouse and chick embryos were used as a model for human embryos to test the impact of drugs or chemicals.
This takes us back to our first research, in which a mouse embryo was used to illustrate that the heartbeat occurs earlier than we had thought until now. The researchers consider day 7,5 after conception in a mouse embryo to be the equivalent of day 16 in a human embryo. We can wonder if this conclusion still stands in the light of the new insights on the differences between human and mice and chick embryo’s. Whatever the answer, up to now, most textbooks on embryology have been based on observations back in time that were fine-tuned by findings in mouse and chick embryos. This 3D Atlas is definitely of major interest to the science of human embryology.
Embryo in the Black Box
Now we are talking about getting to know more about embryo's, we cannot go along without paying some attention to the ongoing debate on how far can/should/may we go.
Two recently published studies show that IVF-created embryos can survive outside of the womb for up to thirteen days after fertilisation, instead of the previously assumed maximum of nine days. One of the reasons why we know so little about the earliest stages of human embryologic development is the so called “14-day rule”, that forbids anyone to keep human IVF embryos alive outside of the body beyond that term.
It basically boils down to a gap in research on human embryogenesis between day 14 and day 28 (the moment the tissues of aborted fetuses can be studied). Because we are left in the dark on what exactly happens in that period and how, this period is also called “the black box of human development”. What we know is that “gastrulation” takes places, the embryologic single-layered structure develops into a three-layered one, containing the map and foundations for the development of all our major body systems.
Some researchers are pleading for a debate on extending the 14-day rule in order to gain insight into the “black box period” in the hope of extending our knowledge on a range of issues such as congenital conditions, infertility and miscarriages. This call to break open the black box period has become even louder with the recent progress in using CRISPR-Cas9 systems in genome editing in human cell cultures. Please note that I am not endorsing any of the developments discussed above, neither am I positioning myself in this debate as it extends the scope and purpose of this blog.
While researchers are fascinated by finding the first heartbeat, listening to the heartbeat of their baby is also a special moment for parents. Normally, the heartbeat will be checked on a regular basis during prenatal consultations, by ultrasound or Doppler fetal monitoring. But recently a simple do-it-yourself-at-home solution was presented by Bellabeat.
Bellabeat is a company known for its classy devices to track women’s health and wellness. It recently developed an app and device “to improve the bonding experience” between expecting parents and their unborn child. How does it work?
The free Shell-app simply turns an iPhone into an acoustic horn. When pressed to the mother’s belly in the right place, the app’s algorithm recognises the heartbeat through the iPhone’s microphone and, while filtering out other sounds, amplifies it and broadcasts it over the iPhone’s speaker. The baby’s heartbeat can be shared with others through the app’s recording and sharing options. The quality of the sound can be improved by adding the Shell add-on, an “seashell-shaped” horn on which you can place your iPhone. Apparently there is a huge demand for this Shell add-on, which costs around 70 dollars, because it is already temporarily sold out.
Bellabeat advices to use the Shell-app from 30 weeks of gestation on. The company stresses that it is safe to use, but advises to put your phone in flight mode as a precautionary measure. They also note that the Shell-app is not a medical or diagnostic device and doesn’t replace the advice given to women by health care professionals. They also (rightly) mention that fetal movements are the best indications for the child’s health and refers women to consult their practitioners on these matters.
If you ask me as a midwife whether the Shell-app is love at first sound, I would have to say that I am a bit hesitant. Even though I have a soft spot for exploring new technologies, I feel that the business strategy is to present this type of technology as something that facilitates a better, more intense and even more natural way of listening, connecting, bonding, sharing and experiencing. Personally, I rather think it can endanger the natural intuition of a woman and limit her in developing her senses and using her natural instincts to monitor the wellbeing of her baby. In that sense, it will not be too long before we hear about the woman who, in panic, called her midwife because she couldn’t find her child’s heartbeat or thought the heartbeat was too low, or forgot to mention those reduced fetal movements because she heard a proper heartbeat all the time. I would rather entrust the baby’s health to its mother’s heart than to what she heard.
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R.C.V. Tyser et all. (2016). Calcium handling precedes cardiac differentiation to initiate the first heartbeat. eLife, 5 : e17113. DOI: http://dx.doi.org/10.7554/eLife.17113 For free download and video’s see: https://elifesciences.org/content/5/e17113-download.pdf
First of our three billion heartbeats is sooner than we thought: http://www.ox.ac.uk/news/2016-10-11-first-our-three-billion-heartbeats-sooner-we-thought
Research of Oxbridge BHF Centre of Regenerative Medicine, see: http://www.cardioscience.ox.ac.uk/bhf-centre-of-regenerative-medicine
De Bakker, B.S. et al. (2016). An interactive three-dimensional digital atlas and quantitative database of human development. Science 354, 6315. DOI: 10.1126/science.aag0053 See http://science.sciencemag.org/content/sci/354/6315/aag0053.full.pdf
3D Atlas of Human Embryology: http://www.3dembryoatlas.com/
3D embryo atlas reveals human development in unprecedented detail, Nicole Davis, 24-11-2016, The Guardian, see: https://www.theguardian.com/science/2016/nov/24/3d-embryo-atlas-reveals-human-development-in-unprecedented-detail
Virtual Human Embryo (VHE) Project - A Digital Image Database of Serially Sectioned Human Enbryos form the Carnegic Collection, see: http://virtualhumanembryo.lsuhsc.edu/default.htm
Article by Steve Connor in “The Guardian”, 5 June 2016. Inside the ‘black box’ of human development Researchers will soon have the means to study embryos beyond the 14-day legal limit. Does the potential for advances in medicine outweight ethical concerns? Online available at: https://www.theguardian.com/science/2016/jun/05/human-development-ivf-embryos-14-day-legal-limit-extend-inside-black-box
For a Special in Nature on CRISPR, see: http://www.nature.com/news/crispr-1.17547