How Ancient Viral Elements Influence the Risk of Preeclampsia During Pregnancy

Genetic elements derived from ancient viruses integrated into our DNA play a key role in the development of the placenta and may explain certain risks of preeclampsia, a serious pregnancy complication specific to humans. A recent study reveals how two of these elements, called LTR8B and MER65, alter the activity of a protein named PSG9, which is essential for the formation of placental cells.

The placenta is a rapidly evolving organ that differs between species. In humans, it is particularly complex and can malfunction, leading to diseases such as preeclampsia, characterized by hypertension and organ damage in the mother. Researchers have discovered that LTR8B acts as a genetic switch controlling the expression of PSG9, a protein involved in the fusion of placental cells into a syncytial layer, which is crucial for a successful pregnancy. Normally, PSG9 exists in two forms: one anchored to the cell membrane and another secreted into the maternal circulation. MER65, another viral element, enables the production of the secreted form by modifying the end of PSG9’s genetic message.

In women with early-onset preeclampsia, levels of secreted PSG9 are abnormally high. This increase is linked to a disruption of two transcription factors, GATA3 and DLX5, which normally regulate LTR8B activity. When LTR8B is experimentally suppressed, PSG9 production drops, and placental cells lose their ability to differentiate properly. This suggests that PSG9 could serve as an early marker for detecting preeclampsia, a disease that is difficult to predict and endangers both mother and child.

These findings show that viral sequences, once considered useless remnants, have been repurposed by evolution to play a crucial role in pregnancy. Their dysfunction may explain why some women develop preeclampsia, paving the way for new screening tests and a better understanding of the mechanisms underlying this disease. Genetic variations in the PSG9 region, which are common depending on ethnic origin, may also influence individual risk. These viral elements, by interacting with human genes, illustrate how evolution has shaped essential biological functions while creating vulnerabilities specific to our species.

Site Sources

Official Study Source

DOI: https://doi.org/10.1186/s13059-026-03944-z

Title: Endogenous retroviral elements LTR8B and MER65 rewire PSG9 regulation to control trophoblast syncytialization and pre-eclampsia risk

Journal: Genome Biology

Publisher: Springer Science and Business Media LLC

Authors: Manvendra Singh; Yuliang Qu; Amit Pande; Julianna Zadora; Florian Herse; Martin Gauster; Xuhui Kong; Rongyan Zheng; Rabia Anwar; Katarina Stevanovic; Ralf Dechend; Marie Cohen; Attila Molvarec; Jichang Wang; Miriam K. Konkel; Bin Zhang; Cedric Feschotte; Gabriela Dveksler; Sandra M. Blois; Laurence D. Hurst; Zsuzsanna Izsvák