Department of Histology and Embryology, School of Medicine, Akdeniz University, 07070, Antalya, Turkey.
Department of Obstetrics, Gynecology and Reproductive Sciences, School of Medicine, Yale University, New Haven, CT, USA.
J Assist Reprod Genet. 2023 May;40(5):1117-1134. doi: 10.1007/s10815-023-02754-7. Epub 2023 Mar 1.
The foremost drawback of ovarian tissue cryopreservation and re-transplantation (OTCT) technique is the rapid loss of the primordial follicle (PF) pool. In recent studies, we have demonstrated that post-transplantation burnout of the PFs occurs due to the altered expression of the activatory and inhibitory proteins that control PF reserve, and rapamycin prevented it.
Here, we investigated whether anti-Mullerian hormone administration in the bilateral oophorectomy and transplantation group and internal AMH in the unilateral oophorectomy and transplantation group protect follicle reserve by regulating the expression of the molecules that control follicle growth after OTCT in mice.
After 14 days of OTCT, PF reserve is significantly reduced in both unilateral oophorectomy and transplantation and bilateral oophorectomy and transplantation groups, while anti-Mullerian hormone treatment attenuates PF loss after bilateral oophorectomy and transplantation. The expression of KitL, Bmp-15, and p27 decreased after unilateral oophorectomy and transplantation and bilateral oophorectomy and transplantation, yet recombinant anti-Mullerian hormone treatment did not restore the expression of these proteins in the BLO-T group.
Exogenous recombinant anti-Mullerian hormone administration in the BLO-T group preserved the expressions of Tsc1 and Gdf-9 in PF and p-s6k and Gdf-9 in growing follicles after OTCT. Nonetheless, recombinant anti-Mullerian hormone administration did not affect granulosa cell proliferation and death rates in the growing follicles. These findings suggest a novel hormonal replacement strategy for fertility preservation by restoring anti-Mullerian hormone to regulate Tsc1 and p-s6k, thereby linking this hormone with the mTOR pathway and Gdf-9 signaling.
卵巢组织冷冻保存和再移植(OTCT)技术的主要缺点是原始卵泡(PF)池的迅速丧失。在最近的研究中,我们已经证明,PF 储备的激活和抑制蛋白表达的改变导致移植后的 PF 耗竭,而雷帕霉素可以预防这种情况。
在这里,我们研究了在双侧卵巢切除术和移植组中给予抗苗勒管激素(AMH)以及在单侧卵巢切除术和移植组中给予内源性 AMH 是否通过调节控制 OTCT 后卵泡生长的分子的表达来保护卵泡储备。
在 OTCT 后 14 天,单侧卵巢切除术和移植组以及双侧卵巢切除术和移植组的 PF 储备明显减少,而抗苗勒管激素治疗减轻了双侧卵巢切除术和移植后的 PF 丢失。KitL、Bmp-15 和 p27 的表达在单侧卵巢切除术和移植组以及双侧卵巢切除术和移植组中降低,而重组抗苗勒管激素治疗并没有恢复 BLO-T 组中这些蛋白的表达。
在 BLO-T 组中给予外源性重组抗苗勒管激素治疗,在 OTCT 后保留了 PF 中的 Tsc1 和 Gdf-9 以及生长卵泡中的 p-s6k 和 Gdf-9 的表达。然而,重组抗苗勒管激素治疗并没有影响生长卵泡中的颗粒细胞增殖和死亡率。这些发现表明了一种新的激素替代策略,通过恢复抗苗勒管激素来调节 Tsc1 和 p-s6k,从而将这种激素与 mTOR 通路和 Gdf-9 信号联系起来,以保存生育能力。