After years of conducting experiments in the lab, I decided to embark on perhaps the most exciting and challenging experiment in my scientific career: pregnancy. I was always under the impression that, unlike transfecting cells, getting pregnant would prove to be as difficult as rocket science. When the experiment proved to be successful, I was in denial as to the positive result. The reality did not fully set in until the very first ultrasound at 11 weeks of gestation. At this moment, I felt like Dr. Frankenstein staring at the image of a small fetus with a beating heart: this was my creation.
Being a pregnant scientist is exciting. When I told Yuriy, my friend and coincidentally the editor-in-chief of IMMpress Magazine, a couple of months ago that I had actually been enjoying the pregnancy, he exclaimed that I was simply nuts. It is true that women rarely talk about enjoying pregnancy but rather, they are bombarded with either horror stories of developmental defects or unfortunate bodily changes. But as a scientist, the whole process intrigues me. A non-scientist would not typically stop to think about the formation of three germ layers or jump out of a hot bathtub with the realization that “this may be bad for neural tube closure!” And who else would get excited at around 12 weeks of pregnancy because hematopoiesis from the bone marrow has just kicked in? I surely did!
The first trimester of pregnancy is supposedly the hardest due to morning sickness and overall lack of energy. I learned quickly that someone had played a sick joke on newly pregnant women by suggesting that feelings of queasiness, nausea, and upset stomach were restricted to the morning. I assure you that these uncomfortable feelings can strike unexpectedly and inconveniently throughout the day. However, it did seem at its worst in the early morning hours most likely due to an increased stomach acid production from progesterone surges, which serve to relax muscles, including the esophageal sphincter. My routine to keep the queasiness at bay consisted of grabbing an always-present sleeve of crackers from a bedside table upon waking at 4 a.m. Without opening my eyes, I would munch on a few crackers like a blind squirrel before finally racing to the kitchen to have my first breakfast. Lab work was a bit hard, for when this ravenous hunger approached, I would have to immediately stop and flee to the safety of salty crackers. Besides the hunger and fatigue, I noticed an increased sense of smell. This new superpower proved to be very challenging when around growing bacterial cultures.
Worst of all, I felt tired all the time! I would sleep for 12 hours a day and could easily have slept longer. My blood pressure was so low that, on one visit to the doctor’s office, a nurse thought her sphygmometer was broken. It was at this point that I began to take interest in the workings of the immune system during pregnancy. I found out that specialized natural killer (NK) cells in the decidua (a layer of stromal tissue derived from the endometrium), recognize the non-classical HLA-C and -D molecules expressed by the trophoblast and act in the remodeling of tissues and formation of vessels. It was this new vessel formation and an increase in blood flow that was causing my exhaustion. These very same decidual NKs also interact with CD14+ cells found in that milieu to induce Treg migration to the maternal-fetal interface. This, of course, is crucial in preventing rejection of the genetically mismatched alien fetus by the mother.
Even more interestingly, the trophoblast-produced human chorionic gonadotropin (hCG) hormone, which is commonly used in pregnancy tests and acts to promote secretion of progesterone in early stages of pregnancy, also plays a role in this process. It was recently shown that, in addition to its purely “endocrine” function, this hormone chemoattracts Tregs and modulates their suppressive activity. In addition, hCG imposes an immature state on the decidual DCs by suppressing their upregulation of MHC class II and reducing their ability to stimulate T cells. As soon as one can detect pregnancy, the immune response is being altered to tolerate a welcome parasite!
As a T cell researcher, I learned that the first trimester is a prime time for thymus development. Thymic epithelial cells migrate and attach at the pericardium between 7 and 9 weeks of gestation and eventually differentiate into distinct cortical and medullary regions by week 16. Other cell types also appear within the developing thymus and hematopoietic precursors colonize the human fetal thymus as early as 7 to 8 weeks of gestation.
In addition to T cell development, pre-B cells can be identified in the fetal liver at 7 weeks and in the bone marrow by 12 weeks of gestation. Naive B cells migrate to lymph nodes and then to the spleen by week 21. By week 30, the bone marrow becomes the exclusive site for B cell maturation. It is no wonder that a pregnant woman’s energy is so low as it is being appropriated for these immunological processes.
Compared to the first trimester, the second one was a breeze. All of a sudden, I had lots of energy, the unsettled stomach and violent hunger eased and I could again perform lab work for long stretches of time. More importantly, I could now openly “rock” the belly. And I rocked it alright! A very good girlfriend of mine, currently a PDF in developmental biology, accompanied me to my second ultrasound and we “geeked out” at the images on the screen. I was amazed by the resolution and detail of the fetal heart, with its four chambers and blood flow. It was at this time that I found out that I was having a boy.
As the second trimester progressed, my belly began to grow noticeably. If I was ever unsure about the true potential of proliferation and differentiation of cells, I now wondered no more as I was experiencing it first hand. The rate of growth, albeit unseen, absolutely amazed me. As of today, 8 months into the pregnancy, I am beginning to get a bit fearful at the possibility of this endless growth. In the midst of this rapid proliferation and regular fetal movements (sometimes accompanied by a kick or two in the ribs), his organs and bodily systems continue to develop. I can now feel him having hiccups, which is indicative of a proper lung and diaphragm development.
Now that I am in my third trimester, there are new developments to get excited about. Gut microbiota changes tremendously between the second and third trimester. Proteobacteria and Actinobacteria, which are largely absent in the first trimester, are now abundant. Interestingly, in non-pregnant women, presence of these microbes has been associated with inflammation-associated dysbiosis. As pregnancy progresses, metabolic changes take place, including a decrease in insulin sensitivity and accumulation of fat tissue in addition to the production of TNF-a and IL-6. Normally these indexes would be associated with health risks, but in pregnant females these changes are actually beneficial in helping to support and prepare the body for the energetically demanding aspects of lactation.
For many years, the central dogma in the field of developmental biology and immunology was that a fetus does not come in contact with any microbes until birth. Several recent observations have challenged that notion. In mice delivered by C-section, the meconium (the very first poop after birth) harboured normal colonizing species of Enterococcus, Streptococcus, Staphylococcus, or Propionibacterium. Another study showed that when pregnant mice were orally inoculated with a genetically labeled E. faecium strain, the labeled strain could be isolated from the amniotic fluid of the inoculated animals. Human umbilical cord and meconium also have detectable levels of bacteria. Recently, the placenta was shown to harbor over 330 genera and 730 species of microbes, which were closely related to those residing in oral cavities of pregnant women. All this suggests that the fetus is in contact with the mother’s microbiota prior to birth. How this occurs and what effect it has on the developing immune system is still unknown.
Birth is a very exciting biological phenomenon. But perhaps you should ask me how I feel about its “amazingness” in a months’ time. Even after birth, I look forward to watching the newborn grow and knowing that his immune system is constantly encountering microbes to learn what is self from non-self.
Of course, one of the most challenging aspects of having children is the ability to juggle this new responsibility with that of a career. Thus, as previously discussed in the departmental and IMMPress forum, it is my hope that these two choices are not mutually exclusive. I hope that, in addition to having a family, I can also have a great job as a scientist and will continue to be excited about all the biological phenomena and mysteries throughout life.
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