Oxygen, Metamorphosis and Preeclampsia: Amazing Nature
In our perception when someone talks of amazing nature, the reader almost always feels it must be something with natural scenic beauty around us. However being in the field of research and academics for three decades now, I have found natural beauty in each and every natural phenomenon, live tissues, cells and sub-cellular particles. One such natural beauty which for an average onlooker can appear, ugly, is the phenomenon of Obstetric Vasculopathy. Amongst all obstetric vasculopathies, preeclampsia is the one which is most studied and gives us time to go into its depth.
Oxygen is rightly called “Pranvayu” in local vernacular or life-giving air. It is basic to sustenance of all life on this planet. Following this rule the fetal system needs to arrange for a robust and sustained supply of oxygen for its survival and growth. Trophoblasts have been assigned this responsibility. As is well known the cytotrophoblasts undergo a rapid proliferation as soon as implantation occurs. They invade into the maternal tissues to establish the system of oxygenation. This invasion has many other functions too but for the sake of this writing we shall confine to the function of oxygenation. Normally the cytotrophoblasts invade relatively large bore arteries along the decidual wall. These vessels are well-oxygenated. In most of the pregnancies this invasion suffices for establishing the robust and incessant supply of oxygen to the fetus.
In normal ongoing healthy pregnancy, the oxygen pressure in the intervillous space is estimated to be approximately 40 mm of Hg at 8 to 10 weeks gestation. Afterwards at midtrimester when the trophoblastic proliferation and invasion of the endovascular space is complete, the pressure is as high as 90 to 100 mm of Hg. This shows that the invading trophoblasts seek oxygen. Success of these trophoblasts in establishing the oxygen supply decides the success of the pregnancy.
For studying a physiology well, it is sometimes necessary in biological sciences to study the pathological processes. This is true in the current context also. The trophoblasts seek a well oxygenated blood supply which is obtained from large bore spiral arterioles at the decidual surface. In subjects with preeclampsia it has been found that the trophoblasts face a relatively hypoxic environment. As a result they try to invade deeper and even small bore vessels. Again if the oxygen supply gets established, one will find preeclampsia restricted in fury and limited in devastation. However in situations where this supply remains unsatisfactory, the invasion occurs even in much smaller vessels and clinically results in severe forms of obstetric vasculopathies like severe preeclampsia.
There is one vital step remaining in-between, if one is to understand the entire process of etiopathogenesis of preeclampsia. That step is the step of generation of dead-spaces. Incomplete and incompetent invasion by trophoblasts in hypoxic environment at the level of fetomaternal interface leads to generation of dead spaces. It is in these dead spaces that the entire mischief of occurrence of vasculopathy finds its source. However it is beyond the scope of this write-up and so we shall leave it at that.
(For interested readers, please read Obstetric Vasculopathies: http://www.jaypeedigital.com/bookdetails.aspx?id=9789350904510&sr=1. For details of this book click on: http://blessedexistence-blessed.blogspot.in/2013/01/obstetric-vasculopathies-latest-best.html)
The oxygen gradients in the vascular channels that the trophoblasts are invading into are great drivers of the invasion process. It is believed that the sensors in the trophoblasts can sense the suboptimal oxygenation. At the same time this sub-optimal oxygen itself too can drive the proliferation and invasion activity. This means both are responsible – the trophoblasts themselves as well as the oxygenation in the vessels that they are proliferating and invading into. Both are apparently interdependent as judged by different studies of antigenic expression and functioning of certain molecules like Matrix Metalloproteinase.
This entire process of trophoblastic activity goes on well into II trimester and is critical in the understanding the physiology of a healthy pregnancy at the cellular level as well as the etiopathogenesis of when and how things can go wrong.
|Process of metamorphosis in nature|
Concurrently occurring with this process of establishing a well oxygenated supply mechanism for the fetus is a complex but wonderful process of metamorphosis. This transformation occurs in the trophoblasts that go into the spiral arterioles. As is well known, the spiral arterioles though are essentially endometrial vessels but are distinct in the fact that they are lose their muscular wall and as decidual vessels generate a low-resistance vascular bed. This low-resistance blood pool at the fetomaternal interface is critical component of a healthy well-oxygenated supply chain to the fetus.
It is simply wonderful to study and know that the cytotrophoblasts transform themselves into the characteristics of the maternal spiral arterioles which they are invading. If this does not occur the spiral arterioles would cease to function as maternal vascular channels and instead get clogged up. It answers the oft asked question: How do the spiral arterioles remain patent when the solid columns of cytotrophoblastic cells are invading them? The metamorphosis of cytotrophoblasts and acquisition of phenotypic characteristic of spiral arterioles keeps the vessel patent and perfused.
This linkup of the fetus and the mother should be proper at the fetomaternal interface. If this linkage is suboptimal, the result will be obstetric vasculopathy. Interestingly this linkage should occur at both, the placental component as well as the maternal component. If the cytotrophoblasts fail to differentiate and assume maternal phenotypic vascular function early, they result in spontaneous missed abortion. (This term is now replaced by embryonic or fetal demise as per the duration of pregnancy.) This is the earliest manifestation of obstetric vasculopathy.
Such an intricate, well-planned and competently executed natural process occurring away from our eyes but is critical in healthy pregnancy outcome is bound to make an inquisitive scientist awestruck and amazed: Amazing nature indeed!
|Amazing pregnancy intricacies|