By Sandy Hemphill, Contributing Writer, BabyMed
Some complications of pregnancy, such as preeclampsia, begin in the placenta. In such cases, even though the source of the problem is known, treatment is nonexistent because it is almost impossible to treat the placenta without harming the fetus. A multinational team of researchers, however, found that they could successfully overcome certain pregnancy complications by treating the placenta as a “well-controlled tumor.”
“Placentas Behave Like Well-Controlled Tumors”
“They (placentas) grow quickly, produce growth hormones, and invade the immune system” just like cancerous tumors do, according to Lynda Harris, a researcher from the University of Manchester in England who was lead author of the study. Cancer research frequently looks for ways of treating the tumor without causing damage to the surrounding healthy tissue and that is exactly the ideal scenario for treating a malfunctioning placenta, too.
Harris and her research team used mice to study the effectiveness and safety of delivering a growth hormone important to pregnancy using peptide-coated nanoparticles to deliver the hormone. Researchers have demonstrated success with treating cancer when two peptides (chains of amino acids) are used as the delivery vehicle for cancer-killing drugs. The nanoparticles treated with toxic drugs are drawn straight to the tumor without affecting any other parts of the body.
Harris’s research team used the same technique to deliver a growth hormone directly into the placentas of pregnant mice. They used the technique on mice carrying normal-sized fetuses as well as on others carrying smaller-than-normal fetuses (fetal growth restriction). Results included:
- No effect of the hormone on normal-sized fetuses.
- Undersized fetuses grew to healthier sizes.
- No growth hormone was detected in any of the fetuses.
- No growth hormone build-up was detected in the mouse mothers’ bodies.
The peptide delivery system worked to improve the health of the pregnancy without endangering either the fetus or the mother. The mother mice in the study were free of cancer but the possibility exists that if a mother did have cancer, the delivery system might send the growth hormone to the tumor as well. This outcome could prove harmful. If the delivery system were perfected for use on humans, it would be safest if screening for cancer were done before using the nanoparticles.
Maternal and Paternal Biological Conflicts of Interest
A 2012 study describes a battle between maternal and paternal influences on the placenta much like the battle between healthy and cancerous tissues anywhere in the body. The researchers from Yale University suggest this maternal-paternal battle may influence development of preeclampsia.
According to the researchers, it is in the father’s biological best interest to produce a baby as big and robust as possible. The mother’s biological interests also include a healthy baby but it must remain small enough to be safely delivered through her birth canal without endangering her own life. The study describes an ensuing battle between placenta (paternal) and uterus (maternal) that can result in inflammation that leads to arterial damage and, perhaps, preeclampsia.
Paternal Control of the Placenta, Maternal Control of the Uterus
The placenta must draw blood from the uterus to nourish the fetus. To do so, the placenta develops specialized cells called trophoblasts (controlled by paternal influences) that invade the uterus where they attack and destroy blood vessels. This destruction diverts blood into the placenta and provides more nourishment for fetal development.
To fend of the destruction caused by the invading trophoblasts (or any foreign, invasive element), the mother’s immune system produces lymphocytes to fight the invaders and end the arterial damage.
The placenta then launches a counter-attack during which it secretes placental protein 13 (PP13, also known as galectin 13) into the maternal bloodstream. The bloodstream carries the PP13 through the veins, around the placenta, and into the uterus where the maternal immune system attacks the PP13. This battle leaves inflammation and dead cells (necrosis) in its wake, triggering further attention from the maternal immune system.
While the maternal immune system is zeroing in on the uterine tissue damage caused by PP13, the placenta’s trophoblasts continue to infiltrate the mother’s arteries elsewhere and with minimal maternal immunological interference. By fighting the maternal immune system’s "soldiers" on two fronts, the paternal-controlled trophoblasts become more effective in causing arterial damage that frees up more blood for the placenta to nourish an ever-growing fetus.
"We realized that these zones of necrosis are likely occupying the mother's soldiers while the invasive trophoblasts sneak into her arteries, leading to more blood flow to the placenta and a bigger baby. We believe that maintaining this balance could be the key to a healthy pregnancy free from preeclampsia," said Dr. Harvey J. Kliman, a researcher at the Yale University School of Medicine who was part of the study.
Increased understanding of this immunological battle between placenta and uterus could someday lead to ways to predict, prevent, and/or treat preeclampsia. When that knowledge is gained, the peptide-coated nanoparticles may prove to be the ideal delivery system for delivering the necessary drugs to restore balance and health to the placenta and the pregnancy.
Sources:
Harris, Lynda K, et al. "Tumor-homing peptides as tools for targeted delivery of payloads to the placenta."Science Advances 2.5 (2016). American Association for the Advancement of Science. Web. 19 May 2016.
"Battle between the placenta and uterus could help explain preeclampsia."EurekAlert! Yale University, 11 Oct. 2011. American Association for the Advancement of Science. Web. 19 May 2016.
Kliman, HJ, et al. "Placental protein 13 and decidual zones of necrosis: an immunologic diversion that may be linked to preeclampsia."PubMed. Reproductive Sciences / SAGE Publications, Jan. 2012. US National Library of Medicine / National Institutes of Health. Web. 19 May 2016.