Scientists identify early signal of dangerous pregnancy complications

Good news! This could be a breakthrough!

"In a study published today [8/31/2026] ... scientists who analyzed blood samples from thousands of pregnant women found that low levels of a protein called ISM2 during the first trimester were associated with higher risk of both preeclampsia and fetal growth restriction later on.

Follow-up lab studies of placental cells showed ISM2 likely plays a causal role in the disorders, meaning the findings could help in the development of treatments, too. ...

The researchers measured blood levels of nearly 3000 proteins and found one in particular associated with both preeclampsia and fetal growth restriction: ISM2, a little-studied protein produced by the placenta. Specifically, lower blood levels of the protein at the 12-week blood test were linked to higher risks of preeclampsia, fetal growth restriction, or both. ...

What’s more, ISM2 levels were a better predictor of each condition than currently used proteins. ...

In lab experiments, the team found that blocking the production of ISM2 in stem cells that usually develop into normal, uterus-invading EVTs stopped that process from happening.

By contrast, artificially adding ISM2 into a cell line that usually lacks it induced recipient cells to migrate around lab dishes more like EVTs would. ..."

"... Both of these conditions are known to be linked to problems with the placenta not developing properly early in pregnancy, in particular a failure of specialised placental cells known as the extravillous trophoblast (EVT) to invade the mother’s womb and establish a healthy blood supply. ...

Of all mammals, humans have the deepest placental invasion, which reflects the massive demands of oxygen and nutrients required to manufacture the most complex machine ever known, the human brain. ..."

From the abstract:

"Preeclampsia and fetal growth restriction (FGR) are major causes of global morbidity and mortality. 

Both conditions are associated with impaired invasion of the uterus by extravillous trophoblast (EVT).

We performed proteomics in maternal serum obtained at ~12 weeks of gestational age in a prospective pregnancy cohort (Pregnancy Outcome Prediction Study). Here we show that low maternal serum isthmin-2 (ISM2) was the strongest protein signal (out of 2,904) in the first trimester of pregnancy for preeclampsia or FGR.

We validated the association in two independent cohorts (Pregnancy Outcome Prediction Study 2 and Improving Maternal Pregnancy And Child ouTcomes study).

ISM2 protein and mRNA are almost exclusively produced in the placenta, and, within the placenta, ISM2 mRNA is highly enriched in EVT. 

Knocking down ISM2 in cultured human trophoblast stem cells profoundly inhibited EVT invasion.

Conversely, expressing ISM2 in a cell line lacking endogenous ISM2 (HEK293 cells) promoted migration.

We conclude that ISM2 may be causally involved in the early pathophysiology of failed trophoblast invasion and that the protein and its associated pathways are potential targets for the prediction and prevention of preeclampsia and FGR."

Scientists identify early signal of dangerous pregnancy complications | Science | AAAS "Low levels of a placenta made protein predict preeclampsia and fetal growth restriction and could offer new target for prevention"

Pre-eclampsia discovery could lead to new test and treatments for at-risk pregnancies (original news release) "Cambridge scientists have identified a key protein that could act as a predictor for pre-eclampsia and fetal growth restriction, two of the major causes of stillbirth and of sickness among mothers and newborns."

Isthmin-2 is a first-trimester predictor of preeclampsia and fetal growth restriction (open access)

Fig. 2: The association between ISM2 and PE and FGR.

Fig. 3: ISM2 regulates EVT differentiation.

First use of precision editing to alter a single gene to study human embryo development reveals role of master gene

Amazing stuff!

Notice we are now going way beyond the famous CRISPR/Cas9 gene editing!

In my opinion, the first gene to be removed from humans is the sneezing gene!

"Research ... has shown that a genome editing technique can be used to alter a single gene in human embryonic cells, enabling the study of very early human development in unparalleled detail.

The technique, called base editing, is a more precise version of the genome editing technique CRISPR/Cas9. It can change a single nucleotide base pair - the basic building block of DNA - within a human genome of approximately 3 billion base pairs. 

Using base editing, the researchers blocked a gene called NANOG in very early-stage human embryos, and found that the cells of the early embryo could not develop into more specialised pluripotent cells called the epiblast - which later form the body. ..."

From the abstract:

"Understanding how the first cell lineages in human development are specified and maintained has fundamental importance and clinical implications for regenerative medicine, infertility and pregnancy loss.

While mouse models have provided valuable insights into transcription factors regulating early development, translating these findings to human embryos has been limited by ethical, technical and biological constraints.

Functional studies of transcription factors in human embryos have been hindered by nuclease-based genome-editing approaches that induce genotoxicity. 

To overcome this, we applied adenine base editing (ABE8e) to precisely target an exon splice donor site, resulting in a splicing defect and functional knockout of NANOG, representing the first application of base editing to study a developmental regulator in human embryos.

This approach did not trigger genotoxicity and showed limited off-target editing.

Loss of NANOG disrupts pluripotent epiblast specification and instead cells differentiate toward a primitive endoderm (yolk sac) or trophectoderm (placental) transcriptional programme. Retention of primitive endoderm differentiation in NANOG-edited human embryos reveals a functional compensation distinct from mouse, underscoring the importance of directly investigating human development. Our findings demonstrate an essential role for NANOG in human pluripotency and epiblast specification, and highlight the utility of base editing for functional interrogation of human development."

First use of precision editing to study human embryo development reveals role of master gene | University of Cambridge "Scientists have, for the first time, used an extremely precise genome editing technique called base editing to study gene function in human embryos. They found that a gene called NANOG is essential for forming the future body from an embryo."

Base editing reveals an essential role for NANOG in human embryogenesis (no public access)

Day 6 human embryos showing the effect of NANOG presence versus absence. Normal embryo (left)

Racism and socioeconomic stress may alter pregnancy biology, leaving black women nearly three times more likely to die. Really!

Unfortunately, the University of Cambridge also engages in racist propaganda and demagoguery! Very regrettable!

Comparing black and white skinned women is not science, but quackery and junk science!

It is very well known that when you honestly compare women of similar socioeconomic circumstances, backgrounds, family history etc. any differences in health outcomes between black and white women are greatly diminished.

"Black women and their babies face significantly higher health risks during pregnancy and childbirth than white women. Black women in the UK are 2.7 times more likely to die during pregnancy compared with white women, and black babies are more than twice as likely to die before their first birthday as white babies."

Racism and socioeconomic stress may alter pregnancy biology, leaving black women nearly three times more likely to die | University of Cambridge "A University of Cambridge study has found that stresses such as systemic racism and socioeconomic disadvantage may sensitise key processes in the body during pregnancy, helping to explain why black women and their babies face significantly higher rates of complication than white women."

University of Cambridge News