Fertility
Unlocking new potential in stem cell-based embryo models
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.”
Gum disease may impair female fertility by triggering inflammation that affects the ovaries and egg quality, a study in mice suggests.
The findings point to a possible biological link between oral health and unexplained infertility.
Researchers said chronic oral inflammation was linked to oxidative damage, disrupted follicle development and reduced live birth rates in mice.
The study was led by prof Michael Klutstein at the Hebrew University of Jerusalem and prof Asaf Wilensky at the Hebrew University-Hadassah Medical Center, with students Dr Paz Kles and Stephen Ameho.
Scientists examined inflammation linked to dental implants in a mouse model, a common clinical scenario, meaning the research was carried out in animals rather than people.
They tracked how immune signals moved through the body and found the inflammation did not appear to stay confined to the mouth.
Instead, it triggered a systemic immune response, meaning an immune reaction across the body, that reached the ovaries.
The animals had increased levels of inflammatory cytokines in the ovaries. Cytokines are proteins used by immune cells to send signals during inflammation.
Researchers also found changes in immune cell populations, oxidative damage to ovarian tissue, impaired follicle development and reduced oocyte quality.
Oxidative damage happens when harmful molecules damage cells. Oocytes are immature egg cells, while follicles are small structures in the ovaries that contain developing eggs.
These biological changes were linked to reduced live birth rates under inflammatory conditions.
The study also found that oocytes showed DNA damage and epigenetic alterations similar to those seen in reproductive ageing.
Epigenetic changes affect how genes behave without changing the underlying DNA code.
Prof Klutstein said: “Inflammation is often thought of as a localised response, but our findings show that it can have systemic consequences that extend as far as the reproductive system.
“This work suggests that chronic oral inflammation may be an underrecognised factor in female infertility, potentially contributing to cases that currently have no clear explanation.”
The researchers said the findings add to growing evidence linking oral health with overall health.
Chronic oral inflammatory conditions, such as periodontitis, are widespread and have previously been associated with systemic diseases.
Periodontitis is a severe form of gum disease that can damage the tissue and bone supporting the teeth.
The authors said further research in clinical settings would be needed to understand whether the findings translate to patient care.
If confirmed in humans, they said the work could support new approaches to diagnosis and treatment, including anti-inflammatory or antioxidant strategies aimed at improving fertility outcomes.
AI could transform ovarian care by personalising cancer and fertility treatment, but more clinical validation is needed before routine use.
A systematic review and meta-analysis found AI models showed high diagnostic accuracy for ovarian cancer when combining data such as ultrasound scans and blood test results.
Across 81 studies, AI models correctly identified ovarian cancer in around nine out of 10 cases, with pooled rates of 89 to 94 per cent.
They were also highly accurate at ruling out ovarian cancer when it was not present, with specificity of 85 to 91 per cent.
The analysis also found that explainable AI tools could predict complete surgical cytoreduction in advanced ovarian cancer.
Complete surgical cytoreduction means removing all visible cancer during surgery, which can be an important goal in treatment planning.
The tools achieved a pooled AUC of 0.87. AUC is a measure of how well a model distinguishes between different outcomes, with higher scores showing stronger performance.
In reproductive medicine, AI algorithms helped physicians optimise ovarian stimulation protocols and predict follicular growth during IVF.
Ovarian stimulation is the use of hormones to encourage the ovaries to produce eggs, while follicles are the small sacs in the ovaries where eggs develop.
The review found AI could reliably model ovarian response in IVF with a pooled AUC of 0.81.
However, researchers said challenges remain in translating promising research findings into routine clinical practice.
They identified substantial variation across studies, driven by retrospective study designs, variable AI systems and a lack of standardised validation.
Only 22 per cent of analysed studies reported prospective, multicentre external validation, where models are tested forward in time across multiple healthcare settings.
The authors called for rigorous validation to help close the gap between research and routine clinical practice, alongside standardised methodological and reporting frameworks, smooth integration with clinical workflow and robust governance to support responsible and ethical AI use.
They concluded: “Artificial intelligence is a transformative force in the management of ovarian conditions.
“In gynaecologic oncology, AI enhances every phase of care, from early detection and accurate diagnosis to prognostic stratification and surgical planning.”
In reproductive medicine, AI personalises ovarian stimulation and refines the diagnosis of heterogenous endocrine disorders such as PCOS.
PCOS, or polycystic ovary syndrome, is a hormonal condition that can affect periods, skin, weight and fertility.
Housing, work and fertility pressures are stopping many Britons growing the families they want, new research suggests.
A UK fertility report found that 79 per cent of people surveyed who had tried to conceive in the past five years would like more children than they currently have.
Among parents with one child, that figure rises to 88 per cent.
The report surveyed more than 1,000 people across the UK who had tried for a baby in the past five years.
While birth rates continue to fall, the findings suggest it is not because people no longer want children. Instead, many respondents said external pressures are making it harder to grow their families.
The findings, from wellness brand Wild Nutrition’s Fertility Disconnect report, highlight how financial pressures, fertility struggles and gaps in reproductive health knowledge are shaping modern family life in the UK.
Gail Madalena, fertility nutritional therapist at Wild Nutrition, said: “People often assume fertility begins the moment they decide to try [for a baby].
“In reality, egg and sperm health are shaped months and years earlier.
“By the time someone starts thinking about fertility, their body has already been responding to its environment for a long time.”
Among the biggest barriers, 26 per cent said career progression affected their family plans, 25 per cent cited housing affordability and lack of space, and 52 per cent said they required medical intervention during their fertility journey.
The report also found that almost a quarter of respondents had spent more than two years trying to conceive.
Trying for a baby can take a significant toll on mental health and relationships, especially for those navigating fertility treatment.
According to the research, 38 per cent of respondents said trying to conceive had negatively affected their mental health. That figure rose to 99 per cent among people undergoing fertility treatment.
Julianne Boutaleb is a perinatal psychologist.
She said: “Navigating a fertility journey is about so much more than medical appointments and procedures.
“It’s an emotional marathon that can take a huge toll on your mental wellbeing.
“Sadly, the stats show that 15 per cent of couples going through fertility treatment say their relationship has been irrevocably impaired.”
The report also highlighted the realities of secondary infertility, which affects around one in 20 people, challenging the assumption that having one child means conceiving again will be straightforward.
Researchers found many people felt under-informed about fertility, particularly younger adults.
Ten per cent of Gen Z respondents said they “know nothing” about fertility, while only one in five respondents said they know “a lot” about egg health.
The report also found that 60 per cent of women were unaware of fertility testing options, and one in five Gen Z respondents said they felt uncomfortable discussing fertility, even with their partner.
Around 40 per cent of those surveyed supported fertility education being included in schools, covering topics such as egg health, sperm health and hormonal health.
The report also explored how lifestyle and long-term health may influence fertility outcomes.
Many respondents said they only made changes once they started trying to conceive.
Some 44 per cent improved their diet when trying for a baby, while 32 per cent reduced alcohol intake at that stage.
The report also referenced emerging research that suggests ultra-processed foods and microplastics could have an impact on reproductive health.
While fertility conversations often focus on women, the findings showed male fertility issues are also affecting many families.
Seventeen per cent of respondents cited sperm health issues as a barrier to conception, while male factors contribute to around half of all fertility challenges.
Only one in four men said they would share fertility struggles with friends.
“Many causes of male infertility are entirely treatable yet so often the last resort is the first response,” said Ian Stones, co-founder at Test Him Ltd.
The findings come as UK birth rates remain below replacement level.
The report noted that the UK fertility rate is now 1.41, meaning that on average women give birth to 1.41 children over their lifetimes. The replacement rate, or rate that maintains population numbers, is 2.1.
It also said the average age of mothers has risen to 31, while birth rates are falling across most age groups except among over-40s.
“There is no single fertility story, and it is rarely a simple, linear narrative,” said Dr Zeynep Gurtin, lecturer in women’s health at UCL.
Dr Gurtin added that better fertility education, fairer access to treatment and more open conversations around infertility and pregnancy loss are needed.
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