Researchers have uncovered a new facet of the angiotensin-converting enzyme 2 (ACE2), known for its role as a gateway for the novel coronavirus into human cells. The enzyme also plays a crucial part in the development of a healthy placenta during pregnancy. This groundbreaking study, published on February 7 in the journal Cell Death and Disease, utilizes advanced gene-editing techniques on human placental organoids to understand the molecular mechanisms underlying pregnancy complications.
The research team employed stem cells from donated placental tissue to grow organoids—miniature, simplified versions of placentas in laboratory dishes. This innovative approach marks the first time gene editing has been explored in human placental organoids to investigate the molecular roots of pregnancy disorders.
Anya Arthurs, a key researcher in the study, emphasized the importance of understanding these mechanisms.
"I think it's important to know the molecular mechanisms which underpin a pathology. If you don't know the molecular mechanism, you can't design a therapy." – Anya Arthurs
The study revealed that ACE2 is not only pivotal for healthy placenta development but also associated with small-for-gestational-age babies. Researchers observed that having a specific variant in the ACE2 gene increases the likelihood of this condition by 23 times.
"By having [a specific variant in the ACE2 gene], you're 23 times more likely to have a small-for-gestational-age baby." – Anya Arthurs
The researchers designed organoids with different ACE2 gene profiles: one with the normal gene, another without it, and a third with a single building block swapped at a critical site. This comparative analysis sheds light on how changes in ACE2 influence placenta formation and function.
Gloria Valdés, a researcher at the Pontifical Catholic University of Chile, who was not involved in the study, praised the research as "extremely interesting." She noted that this work opens new avenues for exploring pregnancy complications beyond those directly related to ACE2.
The ACE2 enzyme's role extends beyond its anti-inflammatory and anti-proliferative properties. Arthurs highlighted the necessity for balance in these systems within placental tissue.
"It's really important that these two sides of the system exist in a balance in a tissue. If you have only one, you're going to have problems — too invasive, too inflammatory." – Anya Arthurs
Furthermore, Arthurs stressed that an excess of ACE2's anti-inflammatory pathway could hinder successful pregnancy due to improper placental formation.
"And if you have too much of this ACE2 anti-inflammatory, anti-proliferative pathway, you're not going to have a successful pregnancy because the placenta is not going to be able to form the way it should." – Anya Arthurs
The findings of this study not only illuminate ACE2's role in pregnancy but also pave the way for developing therapeutic interventions for related complications. The researchers are optimistic that their techniques could aid in studying other pregnancy issues, such as gestational hypertension and preeclampsia.
Currently, efforts are underway to investigate placental organoids that mirror a preeclamptic placenta. This ongoing research holds promise for deepening our understanding and potentially preventing or mitigating complications arising from ACE2 activity during pregnancy.
