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Scientists develop mini-ovaries that could advance infertility research
Scientists have successfully created laboratory-grown human ovary models from stem cells, marking a potential breakthrough in infertility and reproductive disorder research.
The findings, presented at the Joint Congress of the European Society of Paediatric Endocrinology and the European Society of Endocrinology, offer new insights into female reproductive development.
The miniature organoids replicate key structural and functional features of ovarian follicles, which contain eggs and the cells that nurture them.
Researchers at the Institut Pasteur in Paris developed the models by differentiating human induced pluripotent stem cells into granulosa-like cells—essential for egg maturation—and primordial germ cell-like cells, then combining them to form human ovaroids.
While other ovaroid models exist, this is the first to combine these cell types without using exogenous transcription factors.
“Transcription factors are proteins that bind to specific DNA sequences and turn nearby genes on or off, so using external ones can override the innate genetic programme of the cells, which makes the derived populations unsuitable for disease modelling,” said senior author Dr Anu Bashamboo.
The models could improve understanding of differences in sex development (DSDs), conditions in which sex chromosomes and gonadal or anatomical sex do not align. Though rare (1 in 4,500 births), milder forms affect around 1 in 200 people.
During early human development, gonads begin forming at four weeks and develop into testes or ovaries by week six, making the process difficult to study.
Over the past 15 years, scientists have identified numerous genes involved in atypical gonad development, but around half of DSD cases due to gonad formation still lack a genetic diagnosis.
The same team previously generated Sertoli cells—testicular support cells commonly affected in DSDs—from human stem cells. They showed that Sertoli cells with male chromosomes (XY) and a genetic variant linked to atypical testis development could not form the 3D tubular structures of testis cords.
“By creating human-specific, lab-grown models of both testicular and ovarian development using induced pluripotent stem cells, the research overcomes key limitations in the field—particularly the lack of suitable animal models due to poor conservation of developmental genes and mechanisms across species—and provides a powerful platform for studying gene function in a controlled environment,” said Dr Bashamboo.
The new models offer a scalable system that could aid reproductive disorder research and lead to treatments for ovarian dysfunction and infertility.
“Our work more broadly contributes a scalable, human-relevant model system to developmental biology, reproductive medicine and genetic diagnostics. It bridges the gap between basic science and clinical application, offering tools that could improve diagnostic yields and support the development of targeted treatments for individuals with DSDs and related reproductive disorders, including infertility and certain types of ovarian tumours,” said Dr Bashamboo.
Dr Bashamboo added: “Our model also opens up new possibilities for screening drugs and environmental toxins affecting human gonads, personalised medicine and future therapeutic interventions.”
Simultaneous exposure to toxic chemicals and climate-related heat may be worsening fertility harms across humans and wildlife, research suggests.
The review of scientific literature looks at how endocrine-disrupting chemicals, often found in plastic, together with climate-related effects such as heat stress, are each linked to lower fertility and fecundity, meaning the ability to reproduce, across species including humans, wildlife and invertebrates.
Though the reproductive harms of each issue in isolation are well studied, there is little research on what happens when living organisms are exposed to both.
“Together, the two issues are likely to pose a greater threat to fertility, and the additive effect is “alarming”, said Susanne Brander, a study lead author and courtesy faculty at Oregon State University.
“You’re not just getting exposed to one, but two, stressors at the same time that both may affect your fertility, and in turn the overall impact is going to be a bit worse,” Brander said.
The paper looked at 177 studies.
Shanna Swan, a co-author on the new paper, co-produced a 2017 study that found sperm levels among men in western countries had fallen by more than 50 per cent over four decades. Other research has suggested human fertility has been declining at a similar rate.
The University of Washington’s Institute for Health Metrics and Evaluation has previously said the world was approaching a “low-fertility future”, with more than three quarters of countries below replacement rate by 2050.
The new paper’s authors focused on the effects of endocrine-disrupting chemicals and substances, including microplastics, bisphenol, phthalates and PFAS.
These are thought to cause a range of serious reproductive problems, disrupt hormones and be a potential driver of falling fertility.
Brander said the harms linked to these chemicals are often similar across organisms, from invertebrates to humans.
Phthalates, for example, have been linked to altered sperm shape in invertebrates, spermatogenesis in rodents, meaning sperm production, and reduced sperm counts in humans.
PFAS are also thought to affect sperm quality, and both have been linked to hormone disruption.
The chemicals are widespread in consumer goods, so people are often regularly exposed.
Meanwhile, previous research has shown how rising temperatures, lower oxygen levels and heat stress, among other effects linked to climate change, may also worsen infertility.
Heat stress has been found to affect human hormones, and is linked to spermatogenesis in rodents and bulls.
Research shows temperature also plays a role in sex determination in fish, reptiles and amphibians.
The species has evolved to choose which sex it produces in part based on temperature, and the heating planet can “push it too far in one direction or the other, which overrides that evolutionary benefit”, Brander said.
Similarly, many endocrine disruptors may alter environmental sex determination.
The study set out some of the overlapping effects of chemical exposure and climate change across taxonomic groups, from invertebrates to humans.
In birds, for example, exposure to increased temperature, PFAS, organochlorines and pyrethroids may each individually cause abnormal sperm, increased fledgling mortality, abnormal testes and population decline.
“What happens if they’re exposed to more than one of those stressors at the same time? There has been little exploration of that question.
“Even if there have not been a lot of studies looking at these simultaneously, if you have two different factors that both cause the same adverse effect, then there’s a likelihood that they are going to be additive,” Brander said.
Katie Pelch, a senior scientist with the Natural Resources Defense Council nonprofit, who was not part of the study, said the authors had reviewed high-quality science.
She said she wanted to see more examples of the overlap in impacts, but agreed with the overall premise.
“It is likely [multiple stressors] would have an additive effect, at very least, even if they have different mechanisms of harm,” Pelch added.
The solution to the systemic problems would involve tackling climate change and reducing the use of toxic chemicals.
The study cites the global reduction in the use of DDT and PCBs achieved under the Stockholm Convention as an example of an effective measure, but Brander said much more is needed.
“There is enough evidence in both areas to act to reduce our impact on the planet,” she said.
Home blood pressure checks after hypertensive pregnancy could cut the risk of heart attack, stroke and potentially early death, research suggests.
Women who regularly monitored their blood pressure in the weeks after giving birth, and had doctors tailor their medication if needed, had better functioning arteries nine months later than those who received routine care.
When the medication was adjusted to account for blood pressure changes, the women ended up with less stiff arteries, an effect researchers estimated could reduce the future risk of heart attack or stroke by 10 per cent.
Paul Leeson, professor of cardiovascular medicine who led the study, said the findings suggested that the weeks after birth provided a “powerful and often overlooked opportunity” to protect women’s future health.
“By simply monitoring blood pressure at home, new mothers with hypertensive pregnancies can protect their bodies from future damage,” he said.
High blood pressure, in the form of gestational hypertension or pre-eclampsia, where there are signs of organ damage, affects 5 to 10 per cent of pregnant women.
The condition can damage the mother’s organs and endanger the baby’s life.
Beyond the immediate threat to mother and baby, hypertension in pregnancy can raise the risk of long-term problems, with women three times more likely to develop high blood pressure and twice as likely to have heart disease later in life.
The Oxford team recruited 220 women who developed hypertension in pregnancy. All were on blood pressure medication but were due to reduce their dosage and eventually stop taking the drugs.
In the study, 108 women had standard care in which their medication was reduced based on a few blood pressure checks in the eight weeks after giving birth.
The remaining 112 women used a monitor to check their blood pressure at home each day.
They entered the readings into an app shared with doctors who, if needed, changed their medication day to day, with the aim of giving them better control of their blood pressure.
The new approach led to much better control of the women’s blood pressure, and in tests six to nine months later the women had less stiff arteries.
Stiff arteries are less effective at expanding and contracting, which can drive high blood pressure and ultimately the formation of clots that can block blood vessels and cause heart attacks and strokes.
Trials are now under way to find effective ways of rolling out blood pressure monitoring to women after hypertensive pregnancies. One option is for specialist NHS clinics to deliver the care.
Dr Sonya Babu-Narayan, clinical director at the British Heart Foundation, which funded the work, said the results highlighted a crucial window after birth when paying close attention to blood pressure could help protect women’s heart health for years to come.
“We now look forward to seeing results from larger studies with longer follow-up to see how this might save women’s lives,” she said.
Weight loss jabs are being studied to see if they could help women with polycystic ovary syndrome (PCOS)
The condition, which affects up to one in ten women, changes how the ovaries work and is linked to infertility and weight gain.
Dr Shagaf Bakour has won a £60,000 NHS research grant through Sandwell and West Birmingham NHS Trust to look at whether drugs such as Mounjaro and Ozempic might help.
“The research could lead to earlier support, better long-term health, and more joined-up care for a condition that affects many women but is still often overlooked,” she said.
Women with PCOS have higher levels of male hormones and can suffer from irregular periods and symptoms such as excess body or facial hair, the NHS said.
Associated weight gain can also lead to an increased risk of diabetes and heart problems.
Bakour, a gynaecologist and director of medical education at Aston Medical School, will work with a team to evaluate the effect of the weight loss medicines on metabolic and reproductive outcomes.
The drugs mimic a hormone called GLP-1, which suppresses appetite.
Bakour, alongside Dr Hoda Harb, a consultant obstetrician and gynaecologist at the NHS trust, will review existing evidence on their use and assess how they help patients with PCOS.
“The aim is to give women with PCOS evidence-informed, clearer treatment options and more consistent care,” she said.
“The project hopes to show whether these medicines can improve both general health and fertility health, while also helping local services develop clearer care pathways.
Prof Elizabeth Hughes, director of research and development at the NHS trust, said the effects of PCOS, including infertility, were “very emotive subjects”.
“We should be doing all we can within research and development to advance healthcare for women and to better help future generations with this condition,” she added.
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