State Key Laboratory of Reproductive Medicine, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, 210029, People's Republic of China.
J Ovarian Res. 2019 Jul 19;12(1):65. doi: 10.1186/s13048-019-0541-1.
Premature ovarian insufficiency (POI) is characterized by early loss of ovarian function that affects women before the age of 40. We aim to explore the protective effects of transcutaneous electrical acupoint stimulation (TEAS) against irradiation-induced ovarian damage in mice.
C57BL6 mice were randomly divided into control and irradiation (IR) groups. Then, control group was divided into two treatment subgroups: mock TEAS treatment (control-) and TEAS treatment (control+). IR group was divided into four subgroups according to the time of treatment started: mock TEAS treatment initiated at 2 days after irradiation (IR 2D-), TEAS treatment initiated at 2 days after irradiation (IR 2D+), mock TEAS treatment initiated at 1 week after irradiation (IR 1 W-), and TEAS treatment initiated at 1 week after irradiation (IR 1 W+). The radiation model mice were exposed to single whole body X-ray irradiation (4 Gy), and the control mice received 0 Gy. TEAS stimulation (2 Hz, 1 mA, 30 min/day) was given once a day for six consecutive days per week for 2 weeks. Estrous cycle, ovarian weight, serum AMH level and follicle counts were evaluated. Then, proliferation markers, apoptotic markers and oxidative stress markers were examined.
Compared with the control group, the estrous cycle was disordered, and the ovarian weight, serum AMH, and primordial, primary and secondary follicles counts decreased (all P < 0.01) in the IR 2D- and IR 1 W- groups. In the irradiation with early TEAS treatment group (IR 2D+), the estrous cycle improved, the AMH level and primordial follicular significantly increased compared to the irradiation with mock group (IR 2D-). However, there were no significant differences in the estrous cycle, AMH level and follicle counts between IR 1 W- and IR 1 W+ groups. Moreover, IR 2D+ mice reduced the expression of Bax protein and increased the levels of Bcl-2 and PCNA compared to the IR 2D- group. Furthermore, the early TEAS treated mice showed significantly lower levels of oxidative stress and number of TUNEL (+) granulosa cells than that in the IR 2D- group.
This study is first to evaluate TEAS as a potential therapy to attenuate irradiation-induced ovarian failure through inhibiting primordial follicles loss, increasing serum AMH secretion, inducing antioxidant, and anti-apoptotic systems.
卵巢早衰(POI)的特征是卵巢功能过早丧失,影响 40 岁以下的女性。本研究旨在探讨经皮穴位电刺激(TEAS)对小鼠照射诱导的卵巢损伤的保护作用。
将 C57BL6 小鼠随机分为对照组和照射(IR)组。然后,对照组又分为假 TEAS 处理(对照-)和 TEAS 处理(对照+)亚组。IR 组根据开始治疗的时间进一步分为四个亚组:照射后 2 天开始假 TEAS 处理(IR 2D-)、照射后 2 天开始 TEAS 处理(IR 2D+)、照射后 1 周开始假 TEAS 处理(IR 1W-)和照射后 1 周开始 TEAS 处理(IR 1W+)。将辐射模型小鼠暴露于单次全身 X 射线照射(4Gy),对照组小鼠接受 0Gy。TEAS 刺激(2Hz,1mA,30min/d)每周连续 6 天,每天 1 次,共 2 周。评估动情周期、卵巢重量、血清 AMH 水平和卵泡计数。然后,检测增殖标志物、凋亡标志物和氧化应激标志物。
与对照组相比,IR 2D-和 IR 1W-组动情周期紊乱,卵巢重量、血清 AMH 和原始、初级和次级卵泡计数减少(均 P<0.01)。在早期 TEAS 治疗组(IR 2D+)中,与假照射组(IR 2D-)相比,动情周期改善,AMH 水平和原始卵泡明显增加。然而,IR 1W-和 IR 1W+组之间的动情周期、AMH 水平和卵泡计数无显著差异。此外,与 IR 2D-组相比,IR 2D+小鼠 Bax 蛋白表达减少,Bcl-2 和 PCNA 水平增加。此外,早期 TEAS 处理的小鼠显示出明显较低的氧化应激水平和 TUNEL(+)颗粒细胞数量,与 IR 2D-组相比。
本研究首次评估了 TEAS 通过抑制原始卵泡丢失、增加血清 AMH 分泌、诱导抗氧化和抗凋亡系统,作为一种潜在的治疗方法来减轻照射诱导的卵巢衰竭。