To facilitate successful implantation, endometrial stromal cells (ESCs) differentiate into decidual cells in a process called decidualization. To visualize actin dynamics, the researchers labeled actin proteins with GFP. The group discovered that in ESCs, nuclear actin aggregates into fibers (right) during decidualization, revealing a critical nuclear event in the implantation process. Credit: Kyushu University/Miyamoto Laboratory
Implantation is the first stage of pregnancy, during which the embryo attaches and penetrates the endometrium, the inner tissue layer of the uterus. During this process, endometrial cells change to create the right conditions for the fertilized egg to develop.
Published in Communication biologyA research team led by Professor Kei Miyamoto of the Faculty of Agriculture at Kyushu University, together with Dr Isao Tamura and Professor Norihito Sugino of Yamaguchi University, has elucidated a key step in how endometrial cells change. When endometrial stromal cells, or ESCs, differentiate into cells suitable for egg implantation, the actin in the cell’s nucleus changes dynamically, thereby driving the cell’s differentiation process.
During the early stages of human pregnancy, the uterus undergoes many changes to create an environment conducive to implantation and growth of an embryo. One of these changes is called decidualization. This is when ESCs change their function and morphology and differentiate into decidual cells essential for implantation and maintenance of pregnancy.
“If decidualization is impaired, the embryo cannot be implanted, leading to infertility. However, the regulatory mechanism of decidualization has not yet been completely elucidated,” explains Miyamoto. “Tamura and Sugino’s group previously reported that during decidualization, the expression of many genes changes. To better understand this process at the molecular level, we focused on actin proteins.”
Actin is a component of cell structure, or cytoskeleton, and is known to be involved in changing the shape of a cell, a key step in decidualization. Recently, actin was found to exist in the nucleus of ESCs.
The team began by developing ESCs to visually monitor the behavior of nuclear actin in real time. In their analysis, they found that once decidualization begins, actin in the nucleus aggregates into fibers.
“Interestingly, when cells returned to their original ESC state, nuclear actin aggregates also disappeared. Artificial inhibition of actin aggregate formation inhibited decidualization, indicating that its formation is essential to the process,” continues Miyamoto. “Further analysis revealed that this actin assembly plays a role in suppressing cell proliferation.”
During decidualization, cell proliferation must temporarily stop so that ESCs can begin their differentiation process. The team successfully identified a transcription factor named C/EBPb as the key factor that controls the formation of nuclear actin assembly during this entire process.
This finding elucidates a novel mechanism of nuclear actin-mediated control in the decidualization process and reveals a novel role for nuclear actin in the implantation process.
“It is worth considering targeting nuclear actin dynamics and its regulatory factor C/EBPb to develop new treatments for implantation failure,” concludes Miyamoto.
More information:
Isao Tamura et al, Nuclear actin assembly is an integral part of decidualization in human endometrial stromal cells, Communication biology (2024). DOI: 10.1038/s42003-024-06492-z
Provided by Kyushu University
Quote: Discovery of new regulatory mechanisms in embryo implantation (October 18, 2024) retrieved October 18, 2024 from
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