Fertility
New technique could advance reproductive science
A new study by researchers at Shinshu University holds promise for overcoming significant challenges in reproductive science, marking a major advancement in fertility research.
Mature egg cells, or oocytes, are essential for fertilization in assisted reproductive technologies.
However, some ‘denuded’ oocytes, or those lacking the protective granulosa cell layer, fail to mature.
Now, researchers at Shinshu University have developed a method to culture mature oocytes from these denuded oocytes in the lab.
The new approach holds promise for overcoming significant challenges in reproductive science, marking a major advancement in fertility research.
Assisted reproductive technology (ART) is a fertility treatment where eggs are removed from the ovaries, combined with sperm outside the human body, and the resulting embryos are placed in the uterus.
Typically, eggs or oocytes grow within fluid-filled sacs called follicles in the ovary.
Granulosa cells (GCs) surround the developing egg and provide essential nutrients and hormones.
However, early-stage follicles have only a thin GC layer, and during isolation for fertility treatments, these cells may detach from the egg, leaving behind “denuded” oocytes, which are unable to mature and cannot be used in ART.
Now, in a study published online on 21 August 2024 in Biology of Reproduction, Assistant Professor Kanako Morohaku and her team at Shinshu University have identified a novel method to produce viable, embryo-forming eggs from denuded oocytes taken from “preantral” follicles in mice.
Preantral follicles represent an earlier developmental stage, unlike the more mature antral follicles typically used in ART.
While previous research focused on antral follicles, there have been limited attempts to obtain viable eggs from preantral follicles.
To address this issue, the researchers isolated denuded oocytes and GCs from mice, which were then grown together in a U-shaped lab dish for eight days.
This led to the formation of granulosa cell-oocyte complexes, or GOCs, which allowed the oocytes to interact with supporting cells again.
In a previous study, the team found that oocyte quality was affected by the oxygen concentration under which GOCs were cultured.
Hence, these oocytes were cultured with GCs under high (20 per cent) and low (5 per cent) concentrations of oxygen to observe the difference in oocyte growth.
They observed that low oxygen levels significantly improved the development of GOCs and stimulated the formation of transzonal projections, thin cellular connections necessary for oocyte growth.
After eight days, these reassembled GOCs were cultured on a collagen-coated membrane for four additional days, leading to the maturation of oocytes into fertilizable eggs.
To test their viability, the researchers fertilized the eggs and transferred 126 embryos into female mice, following which they obtained six live pups.
Mr Tomohiro Koham is a PhD student and one of the authors.
He said: “To the best of our knowledge, our new culture protocol is the first to successfully obtain offspring from preantral follicle-derived denuded oocytes grown by reconstructing GOCs in vitro.”
The researchers suggest that this new method could also benefit large animals like cattle and pigs, where typical egg maturation techniques often fail due to the unique structure of their ovaries.
Additionally, the approach could help converse endangered species by supporting ex vivo (outside an organism’s body) production, offering a new way to preserve genetic resources.
Image: Kanako Morohaku at Shinshu University
Onto Health has acquired Levy Health, a fertility software company providing precision diagnostics and patient intake for reproductive medicine.
The acquisition, fuelled by Onto Health’s US$20m Series A fundraise in April, supports its plan to build scalable, tech-enabled infrastructure for reproductive medicine.
Onto founder Roohi Jeelani, MD, called it the first of several moves in the company’s expansion strategy in a LinkedIn post, adding that there was “more coming soon”.
She said: “This isn’t just an acquisition, it’s proof of how we’re building Onto: physician-led, tech-enabled, and built to scale without losing the personal touch fertility patients deserve.”
Headquartered in Chicago, Onto Health combines evidence-based fertility care with artificial intelligence-driven diagnostics, clinical automation and longevity science.
AI-driven diagnostics use software to analyse patient information and support clinical decision-making, rather than replace clinicians.
Levy Health, founded in Berlin with US offices in San Francisco, helps medical providers identify endocrine disorders more quickly and helps clinics streamline fertility workups.
Endocrine disorders affect the body’s hormone system, which can influence ovulation, menstrual cycles and fertility.
Co-founder Caroline Mitterdorfer said joining Onto would expand Levy Health’s fertility care tools to more clinics and patients, helping physicians focus on patient care.
Onto opened its first clinic in Chicago in February, with plans for three more in the greater Chicago area.
The company said in April that it would use its new funding, led by Artis and Humania, to support additional operations in the US and expand into the Gulf Cooperation Council.
The Gulf Cooperation Council includes six Arab states bordering the Persian Gulf.
Softening ageing ovaries could help women remain fertile for longer, early animal research suggests.
Fertility declines with age for several reasons, including poorer egg quality, fewer ovarian follicles and the gradual stiffening of ovarian tissue.
Existing fertility treatments, including hormone therapy and in vitro fertilisation, mainly address hormonal imbalances or help eggs mature or become fertilised.
Scientists are now examining whether changing the physical structure of the ovaries could provide another route for future fertility treatments.
Stuart A. Cook, of the Cardiovascular and Metabolic Disorders Programme at Duke-National University of Singapore Medical School, published an accompanying commentary on the research.
Researchers led by Shixuan Wang at Huazhong University of Science and Technology in Wuhan, China, collected healthy ovarian tissue from younger, middle-aged and older women.
They also examined samples from patients with polycystic ovary syndrome, known as PCOS, premature ovarian insufficiency, or POI, and endometriosis.
PCOS is a hormonal condition that can disrupt ovulation. POI occurs when the ovaries stop working normally before the age of 40, while endometriosis causes tissue similar to the womb lining to grow elsewhere in the body.
Tests of protein levels and gene activity found higher levels of the inflammatory protein interleukin-11, or IL-11, in ageing and diseased ovaries.
In laboratory experiments, the researchers exposed ovarian fibroblasts to IL-11. Fibroblasts are cells that produce connective tissue.
The protein caused the cells to produce excess collagen, a structural material that can build up during scarring and make tissue stiffer.
The researchers then genetically modified mice so they could not respond to IL-11. The animals developed less ovarian stiffening and maintained better ovarian function as they aged.
Similar results were seen in mouse models of PCOS and POI caused by chemotherapy.
In the final part of the experiment, older mice and rats were injected with a nanoparticle treatment containing small interfering RNA, or siRNA, designed to switch off IL-11.
The treatment made the animals’ ovaries less stiff and improved fertility.
Pregnancy rates among older mice rose from 25 per cent to 50 per cent, while average litter sizes also increased.
More rats treated with the therapy became pregnant and produced larger litters.
The approach remains highly speculative and will require considerably more research before its safety or effectiveness in women can be established.
However, the researchers said blocking the inflammatory pathway could eventually form the basis of new fertility treatments.
They said: “We propose that anti-IL-11 therapy represents a promising translational strategy for delaying ovarian ageing.”
W Group has opened applications for W Accelerate with Merck KGaA and M Ventures, inviting reproductive and maternal health startups, scaleups and spinouts to pitch for direct access to global pharma partnership and strategic investment.
Selected companies will pitch on 5th October, competing for the chance to accelerate their growth through commercial partnerships, investment, or both.
This is the third time Merck KGaA, a global leader in reproductive health, has partnered with W Group on the programme, which exists to close the innovation and investment gap in women’s health by connecting the sector’s most promising startups directly with the corporates and investors positioned to scale them.
What Merck KGaA and M Ventures are looking for
This year’s call is focused on breakthrough solutions in female infertility, fertility preservation, adenomyosis, endometriosis, polyendocrine metabolic ovarian syndrome (PMOS), ovarian insufficiency, preeclampsia and pregnancy comorbidities.
New for this round, applicants choose between three pathways depending on what they need from the programme:
- The Partnership Lane, for companies seeking commercial collaborations and strategic relationships
- The Investment Lane, for founders looking to connect with investors and secure funding to scale
- The Dual Lane, for innovators pursuing both partnership and investment opportunities
How the Accelerate event works
Selected companies get a 1:1 pitch practice session ahead of time, then a private 30-minute session with Merck KGaA and M Ventures leadership on the day itself, small-group sessions with regulatory and investment strategy experts, an “Ask Merck Anything” roundtable, and a VIP networking reception.
Key dates
- Open call launches: 8th July
- Open call closes: 2nd September
- Notification of successful companies: 11th September
- Pitch day: 5th October
Applications are open now at wplatform.typeform.com/to/KGzviBQM.
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