Last month, AthenaDAO Science and Deal Flow Co-Lead Anaelle Harel attended the 1st European Ovary Workshop in Lagos, Portugal.

Breaking Free from the Sidelines

By Anaelle Harel

For too long, the ovarian research community has existed at the margins of larger conferences, relegated to specialized sessions and sidelined discussions. But the ovary is no auxiliary organ; it's a strategic orchestrator of systemic health whose influence extends far beyond reproduction. With this understanding, Dr. Christiani Amorim - AthenaDAO collaborator, and Dr. Stine Gry Kristensen created the 1st European Ovary Workshop, marking a landmark moment in reproductive biology.

Last month, I had the honor of representing AthenaDAO at this event. Over four intensive days, researchers, clinicians, and innovators mobilized forces to claim their rightful space. From lab-grown eggs to cancer-resistant ovaries, this was no fleeting assembly. It was a gathering of pioneers intent on redefining what the ovary means, a quiet assertion staking its claim at the forefront of medical research.

I arrived curious; I departed convinced its time had finally arrived.

It Takes a Village to Raise an Egg

Nowhere is the old proverb more true than in the realm of in vitro gametogenesis (IVG), the process of cultivating eggs (oocytes) in a lab using stem cells. From scientists and bioengineers to silkworms, this segment of the workshop revealed not only our progress toward growing eggs outside the body but also how advancement in ovarian science depends on bridging the gaps between domains.

Dr. Katsuhiko Hayashi, traveling from Japan, unveiled how mechanical forces govern oocyte dormancy (a state where immature eggs are kept inactive until needed). Known for his pioneering work in IVG, Hayashi, in collaboration with Dr. Mitinori Saitou, was among the first to transform stem cells into oocytes that, once fertilized, produced healthy pups in 2012. In 2023, he generated mouse oocytes from male stem cells, strategically altering chromosomes to produce pups from two fathers.

Hayashi's talk on mechanical factors highlights oocyte dormancy as a crucial detail in the quest for IVG. In a woman's ovary, dormancy safeguards the egg reserve by ensuring only a few follicles activate each cycle. In vitro, stem-cell-derived oocytes mature too rapidly and perish before reaching their full potential.

In mice, Hayashi strategically outmaneuvered this obstacle by utilizing fetal ovarian cells, mimicking the follicles that typically protect oocytes to recreate the natural dormancy mechanisms. However, scaling to human application faces ethical and practical barriers against using fetal cells. Instead, we must engineer this environment. Understanding the factors controlling dormancy is critical to ensuring eggs survive long enough to function.

Dr. Chiara Di Berardino advances with clear purpose. Her enhanced scaffolds, crafted from poly(ε-caprolactone) through electrospinning, establish a biomimetic foundation supporting early-stage follicles in the lab—not for IVG’s stem cell origins, but as a potential home for oocytes needing dormancy’s protective embrace. Dr. Valentina Di Nisio from the Karolinska Institute builds on this progress; her 'Silk-Ovaroids' poster reveals three-dimensional structures, woven from silkworm-derived protein, that faithfully recreate ovarian tissue. This is no mere shelter; it's a living home where oocytes may persist and mature.

In 2016, Hayashi demonstrated a groundbreaking possibility: eggs formed from stem cells, birthing pups in a lab. Now, researchers at the EOW work to refine these complementary visions, seeking paths of consistency and safety. The journey extends beyond humans—Dr. Andrew Pask presented his work on how techniques like IVG are being applied to de-extinct the Tasmanian tiger, a true testament to the contribution of ovarian research to global conservation efforts.

The potential of these ovarian systems extends beyond IVG's horizon. They provide hope for safer fertility preservation, offering options to many, such as cancer patients whose reproductive future faces uncertainty. This work carries a quiet, steadfast promise.

Safeguarding Future Life

In a world where motherhood still threads deep into female identity, chemotherapy's impact on fertility strikes hard, a consequence often overlooked in the urgent effort to save a life. Standard approaches like egg freezing, which demand weeks of hormone injections and planning, falter under cancer's urgency; time most patients cannot spare. At the European Ovary Workshop, these women weren't statistics; they were the north star.

Dr. Stine Gry Kristensen shared insights on Ovarian Tissue Cryopreservation (OTC), a tool that steps in where other strategies reach limits. A minor surgical procedure extracts a section of ovarian tissue, preserves it in cryogenic conditions, and reimplants it once chemotherapy has concluded. The data is encouraging: in 2017, it was shown that over 130 babies born worldwide owe their existence to this technology.

But Kristensen reminds us that challenges remain. Labs and countries employ different protocols with varied approaches; selection criteria differ, and follow-up studies are inconsistent. A systematic review led by Dr. Hajra Khattak, an organizer of the EOW, revealed a 37% pregnancy rate and a 28% live birth rate following OTC. Though promising, this data underscores the need for improved techniques.

One critical battlefront appears to be the thawing process; frozen tissue awakens sluggishly, its metabolism faltering. Ines Moniz's poster revealed fascinating potential solutions: she's testing Umbilical Cord Mesenchymal Stem Cells (UCMSCs) as supporters. These cells release growth factors and suppress inflammatory responses when cultured alongside the tissue. Her research showed improved mitochondrial function, metabolic activity, and structural integrity. Meanwhile, Dr. Rebekka Einenkel shifted focus to hormone dynamics, examining Follicle-Stimulating Hormone (FSH) and Estrogen post-thaw. Elevated FSH and depleted estrogen reduced VEGF-A, a vital component for blood vessels—suggesting improper hormone balance could compromise the tissue. Her insight? Manipulating hormone levels may enhance recovery.

This isn't merely about preserving fertility, the hope is that OTC could maintain ovarian function in women, delaying the ovarian aging that leaves them vulnerable for far too many years.

Strongholds Against Time

Ovarian aging spares no one. It marks the body's first surrender to time. Follicles diminish, oocytes weaken, and fertility retreats long before other systems falter. Yet this shift extends beyond reproduction. Hormonal depletion triggers bone vulnerability and cardiovascular strain, an accelerated transition into senescence. At EOW, this organ's decline received focused attention. Multiple presentations sought to decode its mechanisms, not only for fertility but for the broader implications for longevity.

Dr. Chen Lesnik from the University of Haifa contributes to this exploration. Her laboratory, investigating aging's mysteries, begins with the female reproductive system. She traces metabolic pathways that deteriorate with time, concentrating on mitochondria, the cell's power centers. These structures generate energy, sustain vitality, and neutralize reactive oxygen species. Oocytes harbor the body's densest mitochondrial concentrations (thousands per egg). When they falter, oxidative damage intensifies, and resilience wanes.

Lesnik's objective is clear: identify these pathways and develop interventions to support them.

Nikoleta Nikou, an AthenaDAO travel grant recipient, continues this work. Her research utilizes SkQ1, a mitochondrial-targeted antioxidant. Unlike conventional antioxidants, SkQ1 concentrates in mitochondria, neutralizing oxidative damage at its source. In mice, her findings reveal that SkQ1 strengthens the ovarian reserve. It mitigates ethanol's effects and moderates natural aging's progression.

The workshop's models expanded this investigation, each providing insights into aging's progression. Dr. Miguel Brieño-Enríquez studies the naked mole-rat (NMR), an exceptional mammal in its longevity. These wrinkled rodents survive to 30 years (ten times a mouse's lifespan). Their ovaries remain active, with follicles persisting into their third decade. Human reserves decline by midlife, but NMRs endure, their mitochondria are protected from reactive oxygen species, and DNA repair mechanisms maintain integrity. Brieno-Enriquez examines this phenomenon, questioning whether its mechanisms could inform our understanding of decline.

Learn more about Miguel’s work as he was featured in AthenaDAO’s first-ever online summit.

Meanwhile, others employ C. elegans, a nematode whose brief lifespan illuminates aging's complexity. Its short life cycle, mapped genetics, and transparent progression reveal mitochondrial degradation clearly. Where human studies would require thousands of eggs, small organisms provide answers efficiently—a practical advantage for discovery.

From Lesnik's exploration of metabolic pathways to Nikou's development of SkQ1, these research efforts advance rapidly from basic science toward interventions with potential clinical impact for preserving ovarian function and addressing age-related fertility decline.

The Ovarian Renaissance

The 1st European Ovary Workshop affirmed a truth long overlooked. The ovary is no mere footnote in human health. It orchestrates fertility, maintains systemic equilibrium, and holds keys to longevity that science is only beginning to decipher.

Though much incredible research from the conference wasn't covered in this article, over those four days I witnessed ovarian researchers from across continents unite with unprecedented collective purpose. From the conservation efforts presented by Dr. Suzannah Williams & Dr. Andrew Pask to Dr. Pauliina Damdimopoulou’s vigilant work against environmental toxicology, the sphere of ovarian research extends its influence across unexpected territories.

As funding priorities shift and cross-disciplinary collaborations form, the ovary's time in the scientific spotlight has arrived. This workshop represents not an endpoint but a beginning, an assertion that ovarian science deserves a central position in our quest to understand health. This inaugural assembly signals recognition that the ovary's wisdom may hold answers to questions we've only begun to formulate — the renaissance has begun.

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