Abstract

BackgroundPremature 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.MethodsC57BL6 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.ResultsCompared 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.ConclusionThis 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.

Highlights

  • Premature ovarian insufficiency (POI) is characterized by early loss of ovarian function that affects women before the age of 40

  • IR group was divided into four subgroups (n = 10 for each group) according to the time of treatment started: mock transcutaneous electrical acupoint stimulation (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+)

  • Anti mullerian hormone (AMH) is produced by the granulosa cells in late prenatal and small antral follicles, and circulating AMH reflects the number of primordial follicles [31]

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Summary

Introduction

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. Premature ovarian insufficiency (POI) is a hypergonadotropic ovarian deficiency with elevated gonadotropins and low estrogen levels that affects approximately 1% women before the age of 40 [1]. Radiation therapy is one of the important etiologies for POI, which has well-documented toxic effects on the reproductive system and the fertility of women [4]. Radiation causes damage mostly via ionization and formation of reactive oxygen species (ROS), and the increased ROS induces rapid primordial follicle loss in the ovaries [9, 10]. Finding an effective and safe protective strategy is critical for both young cancer patients and reproductive scientists

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