Department of Obstetrics and Gynecology, Reproductive Medical Center, Peking University International Hospital, Beijing, China.
HLA Laboratory, Beijing Red Cross Blood Center, Beijing, China.
Mol Reprod Dev. 2024 Feb;91(2):e23731. doi: 10.1002/mrd.23731.
Premature ovarian insufficiency (POI) patients experience a decline in ovarian function and a reduction in serum reproductive hormones, leading to a significant impact on the outcomes of assisted reproductive technology. Despite the absence of an effective clinical treatment to restore fertility in POI patients, recent research has indicated that cord blood plasma (CBP) derived from human umbilical cord blood (hUCB) may offer therapeutic benefits for various degenerative diseases. The primary aim of this study is to explore approaches for enhancing ovarian function and serum reproductive hormones through the administration of CBP in a murine model. Initially, hUCB was utilized to obtain CBP (CBP), which was subsequently analyzed for cytokine and growth factor profiles in comparison to adult blood plasma (ABP) by use of flow cytometry. Subsequently, POI mouse models were established through the induction of 4-vinylcyclohexene diepoxide, followed by the injection of CBP into the tail. At 7, 14, and 21 days posttreatment, mouse ovaries and blood were collected, and their estrus cycle, body weight, and ovarian weights were evaluated using precise electronic balance. Finally, ovarian morphology and follicle number were assessed through HE staining, while serum levels of anti-Müllerian hormone (AMH), estradiol (E2) and follicle-stimulating hormone (FSH) were determined by ELISA. Our study revealed that individuals with CBP exhibited significantly lower concentrations of proinflammatory cytokines, including IL-β (p < 0.01) and IL-2 (p < 0.05), while displaying elevated levels of anti-inflammatory cytokines and chemokines, such as IL-2, IL-4, IL-6, IL-8, IL-12P70, IL-17A, IP-10, interferon-γ, and tumor necrosis factor-α (p < 0.01). Furthermore, CBP demonstrated remarkably higher levels of growth factors, including transforming growth factor-β1, vascular endothelial growth factor, and insulin-like growth factor-1 (p < 0.01) than ABP. Notably, our investigation also revealed that CBP restored the content of serum reproductive hormones, such as AMH, E2, and FSH (p < 0.05), and increased the number of primordial and primary follicles (p < 0.01) and decreased the number of luteal and atretic follicles (p < 0.01) in vivo. Our findings suggested that CBP-secreted cytokines and growth factors could be restored POI ovarian function, enhanced serum reproductive hormones and rescued follicular development in vivo. These findings further support the potential of CBP as a promising strategy in clinical applications for POI related infertility.
卵巢早衰（POI）患者的卵巢功能下降，血清生殖激素减少，这对辅助生殖技术的结局有显著影响。尽管目前还没有有效的临床治疗方法来恢复 POI 患者的生育能力，但最近的研究表明，来源于人脐血的脐带血血浆（CBP）可能对各种退行性疾病具有治疗益处。本研究的主要目的是探索通过向小鼠模型中注射 CBP 来增强卵巢功能和血清生殖激素的方法。首先，我们使用人脐血（hUCB）获得 CBP（CBP），并通过流式细胞术分析其细胞因子和生长因子谱与成人血血浆（ABP）的比较。随后，通过诱导 4-乙烯环己烯二环氧物建立 POI 小鼠模型，然后将 CBP 注射到尾巴中。在治疗后 7、14 和 21 天，收集小鼠卵巢和血液，使用精密电子天平评估其发情周期、体重和卵巢重量。最后，通过 HE 染色评估卵巢形态和卵泡数量，通过 ELISA 法测定血清抗苗勒管激素（AMH）、雌二醇（E2）和卵泡刺激素（FSH）水平。我们的研究表明，CBP 组个体的促炎细胞因子（如 IL-β（p<0.01）和 IL-2（p<0.05））浓度显著降低，而抗炎细胞因子和趋化因子（如 IL-2、IL-4、IL-6、IL-8、IL-12P70、IL-17A、IP-10、干扰素-γ和肿瘤坏死因子-α（p<0.01））水平升高。此外，CBP 组的生长因子（如转化生长因子-β1、血管内皮生长因子和胰岛素样生长因子-1（p<0.01））水平显著高于 ABP 组。值得注意的是，我们的研究还表明，CBP 恢复了血清生殖激素（如 AMH、E2 和 FSH（p<0.05））的含量，增加了原始卵泡和初级卵泡的数量（p<0.01），减少了黄体和闭锁卵泡的数量（p<0.01）。我们的研究结果表明，CBP 分泌的细胞因子和生长因子可能恢复了 POI 的卵巢功能，增强了血清生殖激素，挽救了体内卵泡的发育。这些发现进一步支持了 CBP 作为治疗 POI 相关不孕的一种有前途的临床应用策略的潜力。
