Breakthrough in Reproductive Medicine: Juntendo University's Role

A groundbreaking study led by researchers at Juntendo University in Tokyo has revealed that finerenone, an oral medication primarily prescribed for chronic kidney disease (CKD) associated with type 2 diabetes and chronic heart failure, can effectively restore fertility in women suffering from premature ovarian insufficiency (POI). Premature ovarian insufficiency, also known as primary ovarian insufficiency, is a condition affecting approximately 1 to 3.5 percent of women under the age of 40, characterized by the loss of ovarian function leading to irregular or absent menstrual cycles, elevated follicle-stimulating hormone (FSH) levels, and infertility.

This discovery, published in the prestigious journal Science on February 5, 2026 (DOI: 10.1126/science.adz4075), marks a significant advancement in drug repurposing for reproductive health. Finerenone, marketed as Kerendia, functions as a nonsteroidal mineralocorticoid receptor antagonist (MRA), selectively blocking the mineralocorticoid receptor to prevent fibrosis in target organs like the kidneys and heart. The Juntendo team, in collaboration with the University of Hong Kong, demonstrated that this mechanism similarly alleviates ovarian fibrosis, activating dormant primordial follicles and enabling mature egg development.

In Japan, where fertility rates have hovered around 1.2 births per woman amid growing societal pressures, such innovations from leading medical universities like Juntendo are pivotal. The research not only offers hope to POI patients but also underscores the prowess of Japanese higher education institutions in translational medicine, bridging basic science and clinical application.

Professor Kazuhiro Kawamura, from Juntendo University Graduate School of Medicine's Department of Obstetrics and Gynecology, spearheaded the effort. His prior invention of the in vitro activation (IVA) method in 2013 revolutionized POI treatment by surgically extracting ovarian tissue, activating follicles ex vivo, and reimplanting them. However, IVA's invasiveness—requiring laparoscopy under general anesthesia—limited its accessibility. Finerenone provides a non-invasive oral alternative, administered at 20 mg twice weekly, dramatically reducing patient burden.Explore research positions in reproductive medicine at Japanese universities like Juntendo.

Understanding Premature Ovarian Insufficiency in Japan

POI manifests through symptoms like amenorrhea for at least four months, FSH levels above 25 IU/L on two occasions, and low anti-Müllerian hormone (AMH) levels, often linked to genetic factors (e.g., FMR1 premutation), autoimmune disorders, or iatrogenic causes such as chemotherapy. In Japan, with an aging population and delayed childbearing—average maternal age now over 31—POI exacerbates the nation's low total fertility rate (TFR) of 1.26 in 2024.

Conventional treatments rely on hormone replacement therapy (HRT) for symptom relief or donor eggs for IVF, denying genetic lineage. Juntendo's approach targets residual primordial follicles (estimated 1,000-10,000 per ovary), dormant due to fibrotic ovarian stroma. By softening this stroma, finerenone reactivates folliculogenesis: primordial to primary, preantral, antral, and ovulatory stages.

• Primordial follicle pool preservation despite POI.
• Fibrosis as key barrier, akin to CKD pathology.
• Japan's expertise in gynecology research, with universities like Juntendo leading clinical trials.

This aligns with Japan's national strategy to boost fertility via advanced reproductive technologies, supported by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) funding for higher ed research.

Drug Repurposing: From Kidney Protection to Fertility Restoration

The Juntendo-HKU team employed high-throughput drug repurposing, screening 1,297 FDA-approved drugs using 10-day-old mouse ovarian cells. They monitored Kit ligand (Kitl) expression, a trigger for primordial follicle activation. Finerenone emerged as the top candidate, outperforming others in promoting growth from primordial to antral follicles in organotypic culture.

Step-by-step process:

1. Drug library screening via Kitl promoter assay.
2. In vitro ovary culture: finerenone increased antral follicles 3-fold.
3. Subcapsular transplantation: mature oocytes retrieved.

Mechanistic studies used single-cell RNA sequencing (scRNA-seq) on aged mouse ovaries, revealing finerenone's inhibition of collagen (Col1a1) production in stromal cells, reducing extracellular matrix stiffness and cell-cell signaling that suppresses folliculogenesis.Academic CV tips for reproductive researchers.

Preclinical Evidence: Mouse Models Validate Safety and Efficacy

In aged (10-12 month) C57BL/6 mice, oral finerenone (10 mg/kg, twice weekly for 3 weeks) boosted secondary follicles (p<0.01), antral follicles, and corpora lutea. Young (6-month) treated mice delivered 50% more pups than controls (8.2 vs. 5.4 average).

Safety was rigorously tested:

• IVF from treated oocytes: normal maturation (85%), fertilization (70%), blastocyst rates (40%).
• Embryo transfer: full-term pregnancy, normal litter size, offspring growth, behavior (open field, Morris water maze).
• No chromosomal aberrations or teratogenicity.

siRNA knockdown of Col1a1 mimicked effects, confirming fibrosis pathway.

Clinical Trial Results: Promising Outcomes in 14 POI Patients

The exploratory phase 1/2 trial enrolled 14 Japanese women under 40 with POI (amenorrhea >4 months, FSH >25 IU/L). Finerenone was given orally (20 mg twice weekly) for 3-7 months, monitored by monthly transvaginal ultrasound.

Key outcomes:

No serious adverse events; mild hyperkalemia managed. This contrasts sharply with historical POI IVF success rates near 0% using own eggs.Read the full Science paper.

Mechanism: Targeting Ovarian Fibrosis Like CKD

Finerenone binds selectively to mineralocorticoid receptors in ovarian stromal cells, downregulating fibrosis genes (Col1a1, Fn1). scRNA-seq showed reduced collagen-mediated inhibition of granulosa cell Kitl signaling. Lipid nanoparticle-delivered siRNAs replicated effects, proving causality.

In POI ovaries, fibrosis traps follicles; finerenone 'unlocks' them, mimicking anti-fibrotic kidney benefits. This parallels SGLT2 inhibitors' repurposing in other fields, highlighting Japan's strength in precision medicine.Japan higher ed opportunities.

Comparison to Existing POI Therapies

• IVA (Kawamura's 2013 method): 25-30% live birth rate, but surgical risks, ~10% success per cycle.
• HRT + Donor IVF: No genetic link, psychological burden.
• Finerenone: Oral, low-cost (~$50/month), 100% follicle response in trial, combinable with IVF.

Finerenone's profile suits Japan's IVF clinics, over 500 nationwide, with Juntendo training future specialists.

Implications for Japanese Fertility Landscape

Japan faces a fertility crisis: 2025 births projected at 720,000, down 5%. POI contributes, with 50,000+ affected women. This therapy could add thousands of autologous IVF cycles annually. Economically, CKD drug repurposing cuts R&D costs (finerenone approved 2021).

For higher education, Juntendo exemplifies interdisciplinary research: OB/GYN, pharmacology, bioinformatics. Attracts global talent; faculty positions in reproductive sciences booming.

Stakeholder Perspectives and Challenges

Prof. Kawamura: "We aim to optimize stimulation protocols and explore superior agents." Patient advocates praise accessibility; ethicists note need for larger RCTs. Challenges: hyperkalemia monitoring, optimal dosing, long-term offspring data.

In Japan, MHLW may fast-track approval; universities like Keio, Tokyo U. eye collaborations.

Future Outlook: Multicenter Trials and Beyond

Plans include international phase 3 trials (Japan, HK, US) this year, targeting 200+ patients. AI-optimized screening for next-gen MRAs. Impacts higher ed: more grants, PhD programs in epigenetics/fibrosis.

Actionable insights: POI patients consult specialists; researchers apply for RA roles; academics leverage for tenure.Postdoc advice.

Photo by Jackie Alexander on Unsplash

This Juntendo-led innovation positions Japanese universities at the forefront of global reproductive research. For career opportunities, visit higher-ed-jobs, rate-my-professor, higher-ed-career-advice, or university-jobs. Share your thoughts below.