Connect with us

Fertility

Unlocking new potential in stem cell-based embryo models

Published

on

Researchers have identified Nr1h2, a critical transcription factor essential for early embryo development. The findings enhance our understanding of gene regulation during blastoid formation and hold promise for regenerative medicine, fertility treatments, and developmental biology research.

At the earliest stages of life, the blastocyst—a highly organised structure critical for implantation—begins to form. Its development is tightly controlled by genetic and epigenetic programmes.

Stem cell-based embryo models, such as blastoids, serve as models of the blastocyst and are invaluable tools for studying embryogenesis and early human development. However, the variability in blastoid induction has limited their utility, due to a limited understanding of the genetic drivers of blastoid formation.

The researhers addressed this gap by uncovering the role of Nr1h2 in regulating stem cell fate and driving high-quality blastoid formation.

Using a loss-of-function screen, the researchers pinpointed Nr1h2 as a key transcription factor conserved across mammalian species. Nr1h2 activation was sufficient to enhance the functional and genetic fidelity of stem cell-derived embryo models.

To test Nr1h2’s potential, the team treated embryonic stem cells with the small-molecule agonist T0901317. The treated cells, termed NrESCs, exhibited expanded pluripotency, expressing canonical markers and generating both embryonic and extra-embryonic lineages.

Transcriptomic and epigenetic analyses showed that NrESC-derived blastoids closely resembled natural blastocysts, surpassing current EPSC-derived models in genetic and physiological fidelity.

“Nr1h2 activation rewires embryonic stem cells into an expanded pluripotent state, creating a robust platform to study early developmental processes and identify therapeutic targets,” said Dr Jonathan Yuin-Han Loh of the A*STAR Institute of Molecular and Cell Biology (IMCB).

Therapeutic potential

The discovery also has profound implications for reproductive health. Trophectoderm cells, essential for implantation, were more physiologically faithful in NrESC-derived blastoids.

When transferred into mice, these blastoids achieved significantly higher implantation rates compared to EPSC-derived counterparts. Nr1h2 activation also enhanced blastocyst generation in both mice and pigs, suggesting a highly conserved mechanism across species.

Nr1h2’s identification as a master regulator of early embryogenesis opens new avenues for developmental biology. By refining stem cell-based embryo models, this discovery supports the design of targeted therapies, advances regenerative medicine, and improves our ability to explore the earliest stages of life.

The team’s work sets the stage for future research into transcriptional networks and their role in lineage determination.

“Stem cell-based embryo models are revolutionising drug discovery and reproductive biology,” Dr Loh said.

“Our findings demonstrate that activating Nr1h2 enhances the fidelity of these models, providing an innovative approach to tackle developmental disorders, infertility, and beyond.”

Fertility

Paracetamol use may impact future fertility, studies suggest

Published

on

Paracetamol use in pregnancy was not linked to autism or ADHD, while separate research found reproductive differences in girls exposed before birth.

One study analysed health records from more than 120,000 children and found no increased risk of autism following prenatal paracetamol exposure.

A separate analysis of nearly 100,000 children also found no increased risk of ADHD among those born to mothers who used the painkiller during pregnancy.

Researchers from the Hong Kong Hospital Authority examined electronic health records covering pregnancies between January 2001 and December 2023.

The autism analysis included 124,333 children, who were nine years old on average and split almost evenly between males and females. There were 3,445 autism diagnoses, representing 2.8 per cent of the group.

The ADHD analysis involved 97,285 children, who were seven years old on average and also split evenly between males and females. There were 5,168 ADHD diagnoses, representing 5.3 per cent.

Women prescribed paracetamol during pregnancy were more likely to be older and have pre-existing conditions including psychiatric disorders, as well as reasons for taking the drug such as infection, fever or chronic pain.

No association was found between prenatal paracetamol exposure and either autism or ADHD.

The findings did not differ according to the trimester in which paracetamol was taken or whether use was intermittent or daily. Advanced maternal age, defined as pregnancy in women over 35, did not alter the findings.

The researchers wrote: “Paracetamol remains a safe and essential analgesic [pain reliever] and antipyretic [fever reducer] during pregnancy, whereas alternatives, such as NSAIDs and opioids carry well-documented risks.

“Unwarranted reluctance to use paracetamol could lead to undertreatment of pain and fever, or the use of more harmful alternatives, both posing risks to the pregnancy and developing fetus.”

The authors said women should assess paracetamol use with guidance from their doctor.

A separate study involving 685 pregnant women without pre-existing conditions and 302 infant daughters found associations between prenatal paracetamol exposure and differences in reproductive organs and hormone levels.

Researchers from Copenhagen University Hospital enrolled the women during their first trimester and assessed them during the first trimester, third trimester and again when their babies were three months old.

At around three months, infants experience a temporary rise in reproductive hormones sometimes called mini-puberty.

Pregnant participants completed questionnaires every two weeks about their use of pain medicines including paracetamol. Infant girls underwent ultrasound scans of their reproductive organs and blood tests to measure hormone levels.

Researchers also examined a separate group of 1,210 girls followed from infancy to adolescence whose mothers reported paracetamol use during the third trimester.

Three-month-old girls exposed to paracetamol before birth had an average 40 per cent smaller ovarian volume, 13 per cent smaller uterine volume and 23 per cent fewer ovarian follicles.

Girls exposed during the first trimester also had lower levels of Anti-Müllerian hormone, a marker of ovarian function.

Among the older girls, those exposed before birth were more likely to have smaller uteruses at puberty and smaller ovaries during their teenage years.

Dr Margit Bistrup Fischer, lead study author and postdoctoral researcher in the Department of Growth and Reproduction at Rigshospitalet hospital in Denmark, said: “Animal studies have demonstrated that impaired formation of ovarian follicles can lead to reduced fertility and earlier reproductive aging.

“Whether the differences observed in our study have implications for fertility and age at menopause in humans remains unknown and will require long-term follow-up of the girls in our cohort.”

She cautioned that women who had used paracetamol during pregnancy “should not be alarmed by our findings”, as the study found associations rather than direct causation and outcomes for individual women and children are unclear.

“Importantly, our study does not evaluate whether [acetaminophen] causes reproductive problems, nor does it provide evidence that prenatal exposure affects future fertility or age at menopause,” she said.

“Although we observed similar associations in an independent cohort, long-term follow-up is needed to determine whether these early-life differences have any clinical significance later in life.”

Continue Reading

Fertility

Fertility rate in England and Wales hits record low, new figures reveal

Published

on

The fertility rate in England and Wales fell to a record low of 1.39 children per woman in 2025, down from 1.41 a year earlier.

New figures show that parts of London and cities with major universities accounted for many of the areas with the lowest local fertility rates.

The City of London recorded the lowest rate in 2025 at 0.37 children per woman, followed by Cambridge at 0.87 and the London boroughs of Islington and Westminster at 0.90.

The Office for National Statistics (ONS) defines the fertility rate as the average number of live children women would expect to have over their childbearing lives.

Brighton & Hove recorded a rate of 0.95, followed by Southwark at 0.97 and Norwich at 0.98.

Exeter, Oxford and York, along with the London boroughs of Camden and Hammersmith & Fulham, each recorded 1.01 children per woman.

At the other end of the table, Pendle in Lancashire and Luton in Bedfordshire had the highest rate at 1.93.

They were followed by Oldham in Greater Manchester at 1.87, Bradford in West Yorkshire at 1.84 and Barking & Dagenham in London at 1.83.

The overall fertility rate for England and Wales declined from 1.41 in 2024 to 1.39 in 2025.

A rate of around 2.1 is needed for a population to remain stable over time when the impact of migration is excluded.

Twelve of the 25 local authorities with the lowest fertility rates in 2025 were in London.

In Wales, Swansea recorded the lowest fertility rate at 1.18, while Carmarthenshire, the Isle of Anglesey and Newport each had the highest rate at 1.48.

There were 585,396 live births in England and Wales in 2025, down from 594,677 in 2024 and the lowest number since 1977.

Live births fell across every region in England. The West Midlands recorded the largest percentage decline at 3.1 per cent, while the North East had the smallest at 0.3 per cent.

The average age of parents also increased slightly.

Mothers had a provisional standardised mean age of 31.1 in 2025, compared with 31.0 in 2024. Fathers had an average age of 34.0, up from 33.9.

In 1975, the average age was 26.4 for mothers and 29.5 for fathers.

The proportion of births where the mother was born outside the UK also increased, from 20.8 per cent in 2005 to 27.5 per cent in 2015 and 34.6 per cent in 2025.

India was the most common country of birth for non-UK-born mothers in 2025 for the fourth consecutive year.

It was followed by Pakistan, Nigeria and Romania.

In 2025, 56.4 per cent of births were to parents who were both born in the UK, down from 62.7 per cent in 2015.

Continue Reading

Fertility

Weight loss surgery improves menstrual health and PMOS symptoms, study finds

Published

on

Weight loss surgery was linked to more regular periods and fewer polyendocrine metabolic ovarian syndrome (PMOS) symptoms in women aged 18 to 45 living with obesity in a recent study.

The researchers recommend that women undergoing the procedure have access to preconception care and reproductive counselling to support their reproductive health.

Researchers at the University of Surrey analysed data over 24 months from 84 women who underwent bariatric surgery and 18 women living with obesity who did not have surgery.

Of those who underwent surgery, 49 had gastric bypass procedures and 35 had gastric sleeve surgery.

Women who underwent metabolic bariatric surgery lost more than 30kg on average at 12 and 24 months after the procedure.

Among women with polycystic ovaries, the condition persisted in only 10 per cent after 24 months.

Women also reported a resolution of clinical hirsutism, or excess body hair, by 12 months.

Women who had previously experienced irregular periods reported more regular menstrual cycles after surgery.

Professor Martin Whyte, co-author of the study and professor of metabolic medicine at the University of Surrey, said: “A large proportion of those undergoing bariatric surgery are women of reproductive age, who may be planning a pregnancy in the coming years.

“So much remains unknown about the impact of this type of surgery on women who are planning to have children.

“This raises the question of when the ideal time after surgery is to conceive.”

Women have a higher prevalence of obesity than men, with 57 per cent of women in the UK classified as overweight and 27 per cent living with obesity, which can affect fertility and the health of an unborn baby.

The researchers said 17 women had healthy pregnancies following surgery.

Although this was not specifically examined in the study, no difference in birth weight was observed between babies conceived within or after the first year.

Dr Kathryn Hart, co-author of the study and associate professor in nutrition and dietetics at the University of Surrey, said: “What we have found is that bariatric surgery positively affects the reproductive health of women living with obesity and can improve the likelihood of them having a healthy pregnancy after surgery.

“Dysregulated hormone levels, irregular periods and conditions such as polycystic ovaries are affected by obesity.

“By reducing this, what we have seen is that it can lead to improvements without the need for medication.

“We would suggest that clinicians consider medical intervention for obesity to treat irregularities in the menstrual cycle and issues with fertility.”

Continue Reading

Trending

Copyright © 2025 Aspect Health Media Ltd. All Rights Reserved.