Cytokine-Rich Serum Outperforms Platelet-Rich Plasma in Shielding Rat Ovaries from Reperfusion Damage

Ovarian torsion is one of the most time-critical emergencies in gynecology. When an ovary twists on its supporting ligaments, blood supply is cut off, and the organ begins to die within hours. Yet the cruel irony of the condition is that the surgery itself, detorsion, which restores blood flow, can inflict a second wave of damage known as ischemia-reperfusion injury. As oxygen floods back into starved tissue, a cascade of reactive oxygen species, inflammatory signaling, and programmed cell death can destroy follicles that had survived the initial ischemia, threatening fertility in patients who are often young women of reproductive age. A new study published in Reproductive Sciences by Erol Karakaş and colleagues now offers a fresh perspective on how this damage might be blunted, and the results point to an unexpected frontrunner among regenerative blood-derived therapies.

The research team set out to compare two biological treatments that have generated considerable excitement in reproductive medicine: platelet-rich plasma, widely known as PRP, and a less familiar preparation called autologous cytokine-rich serum, or ACRS. Both are derived from a patient’s own blood, which makes them attractive from a safety standpoint because they minimize the risk of immune rejection or disease transmission. PRP is prepared by concentrating platelets, the tiny cell fragments that orchestrate clotting, in a small volume of plasma. When activated, these platelets release a payload of growth factors, including vascular endothelial growth factor and platelet-derived growth factor, that stimulate tissue repair, new blood vessel formation, and cell survival. ACRS, by contrast, is produced by incubating whole blood in a special container that encourages white blood cells to secrete a broad spectrum of anti-inflammatory cytokines into the serum, which is then harvested for injection.

To test how the two preparations stack up against each other, the researchers turned to a well-established animal model. Forty-two female Wistar albino rats were randomly assigned to seven experimental groups: a healthy control group, groups receiving PRP or ACRS alone, an ischemia-reperfusion group, two treatment groups in which the animals underwent ovarian torsion and then received one of the two therapies, and a donor group that supplied the blood products. The injury was induced by twisting the ovary for two hours, a duration chosen to produce substantial but not total tissue destruction, followed by surgical detorsion to restore perfusion. Immediately after blood flow returned, the animals received either PRP or ACRS. This design allowed the team to isolate the specific contribution of each treatment to tissue rescue in the critical window that follows reperfusion.

The damage caused by ischemia and reperfusion was unmistakable under the microscope. Ovaries subjected to torsion and detorsion without treatment showed severe histopathological changes: widespread degeneration of ovarian follicles, the structures that house developing eggs; congestion of blood vessels; hemorrhage into the tissue; edema, or fluid accumulation; alterations in the connective tissue of the ovarian stroma; and infiltration by inflammatory cells. The molecular analysis told the same grim story. Immunohistochemical staining revealed elevated levels of cleaved Caspase-3, a protein that serves as a molecular executioner in apoptosis, or programmed cell death, confirming that follicular cells were actively dying. At the same time, immunoreactivity for anti-Müllerian hormone, or AMH, a marker of the ovarian follicle reserve and a key indicator of reproductive potential, was diminished, reflecting the loss of viable follicles.

Against this backdrop of destruction, both therapies delivered meaningful protection. Rats treated with PRP or ACRS after detorsion showed significantly less histological injury, reduced apoptotic activity, and better preservation of their follicle populations compared with untreated animals. The finding is consistent with a growing body of literature on PRP in reproductive medicine. Previous experimental work had already demonstrated that PRP can protect the rat ovary from ischemia-reperfusion damage, and clinical studies have explored intraovarian PRP injection in women with poor ovarian reserve and primary ovarian insufficiency, with some reports of improved ovarian function and assisted reproduction outcomes. The present study extends this evidence by directly benchmarking PRP against a competing blood-derived product under identical injury conditions.

The most striking result, however, was that ACRS consistently outperformed PRP across several key measures. Ovaries treated with the cytokine-rich serum showed better preservation of primordial follicles, the dormant reserve of eggs that represents a woman’s lifelong reproductive potential, as well as better preservation of tertiary follicles, the mature fluid-filled structures closest to ovulation. The number of atretic follicles, which are follicles undergoing degeneration, was lower in the ACRS group. At the molecular level, ACRS-treated ovaries displayed higher AMH immunoreactivity, signaling a better-maintained follicle reserve, and lower cleaved Caspase-3 immunoreactivity, indicating that fewer cells were undergoing apoptosis. The treatment also boosted immunoreactivity for VEGFA, the primary driver of angiogenesis, suggesting that ACRS may promote the revascularization needed to sustain recovering tissue after reperfusion.

Why might a serum rich in cytokines beat a concentrate rich in platelets? The authors’ findings suggest that the answer may lie in the breadth and balance of the signaling molecules each preparation delivers. PRP is dominated by platelet-derived growth factors that primarily stimulate proliferation and repair, whereas ACRS contains a cocktail of cytokines secreted by leukocytes that includes potent anti-inflammatory mediators. Because reperfusion injury is fundamentally an inflammatory and oxidative event, driven by an overexuberant immune response to restored oxygen supply, a therapy tuned to dampen inflammation may be particularly well suited to the moment of detorsion. The elevated VEGFA signal observed with ACRS also hints at enhanced angiogenic support, which could help re-establish the microvascular network that ischemia disrupts, delivering oxygen and nutrients to salvageable follicles before they cross the point of no return.

Not every measured parameter separated the two treatments. Immunoreactivity for alpha-smooth muscle actin, or α-SMA, a marker associated with myofibroblast activity and stromal fibrosis, did not differ significantly among the groups. This suggests that neither therapy dramatically altered the fibrotic remodeling component of the injury response in this model, at least within the timeframe studied. It is a reminder that regenerative therapies are not uniform panaceas; they modulate specific biological pathways, and their effects can be selective. The absence of a difference in α-SMA also provides a useful internal control, indicating that the differences the team did observe in follicle survival, apoptosis, AMH, and VEGFA were genuine treatment effects rather than a global artifact of the experimental procedure.

The implications for clinical practice are tantalizing but must be tempered by the usual caveats of translational research. This was a rat study, and rodent ovaries differ from human ovaries in follicle dynamics, lifespan, and response to injury. The two-hour torsion window, while clinically relevant, does not capture the full spectrum of delays patients experience before reaching surgery. Moreover, the treatments were administered immediately after detorsion, whereas in real-world settings, diagnosis and intervention often involve delays. Nonetheless, the study addresses a genuine unmet need. Fertility preservation after ovarian torsion currently relies almost entirely on swift surgical detorsion, with few adjunctive options supported by strong evidence. If the protective effects of ACRS translate to humans, a single autologous injection at the time of surgery could become a practical addition to the operative protocol, using blood drawn from the patient herself.

The work also adds to a broader shift in regenerative medicine toward personalized, blood-derived biologics. ACRS has previously been investigated for degenerative joint disease, where autologous conditioned serum has shown promise in modulating cartilage metabolism and inflammation, and PRP has been applied across orthopedics, dermatology, and gynecology. The idea that different blood-derived preparations, each with a distinct molecular signature, can be matched to specific pathological processes represents a maturing of the field beyond the early enthusiasm for PRP as a one-size-fits-all remedy. For ischemic ovarian pathologies, whether caused by torsion, transplantation of ovarian tissue, or chemotherapy, the Karakaş study suggests that the cytokine-rich fraction of autologous blood may hold particular promise. Larger animal studies and, ultimately, carefully designed clinical trials will be needed to determine whether the histological and molecular advantages of ACRS over PRP translate into preserved fertility in patients, but this research provides a compelling experimental foundation for that next step.

Subject of Research: Comparative protective effects of cytokine-rich serum and platelet-rich plasma against ovarian ischemia-reperfusion injury in rats

Article Title: Comparative Therapeutic Effects of Cytokine-Rich Serum and Platelet-Rich Plasma in a Rat Model of Ovarian Ischemia-Reperfusion Injury

Article References: Karakaş, E., Erol, H., Ermiş, M., Akçakavak, G., Aslan, N. E., & Karataş, Ö. (2026). Comparative Therapeutic Effects of Cytokine-Rich Serum and Platelet-Rich Plasma in a Rat Model of Ovarian Ischemia-Reperfusion Injury. Reproductive Sciences. https://doi.org/10.1007/s43032-026-02223-3

Image Credits: AI Generated

DOI: 10.1007/s43032-026-02223-3

Keywords: ovarian torsion, ischemia-reperfusion injury, platelet-rich plasma, cytokine-rich serum, fertility preservation, ovarian follicles, anti-Müllerian hormone, apoptosis, angiogenesis, regenerative medicine, reproductive medicine, rat model