Diminished ovarian reserve induced by X-ray radiation-induced abscopal effects in mice: an experimental study
10.3760/cma.j.cn101441-20220117-00027
- VernacularTitle:X射线辐射远端效应诱发小鼠卵巢储备功能下降的实验研究
- Author:
Ying ZHOU
1
;
Yanyan GUO
;
Yan LI
;
Shuting YE
;
Bumei ZHANG
;
Xiaopei LI
;
Jianmei WANG
;
Yongrui DU
Author Information
1. 天津医科大学第二医院计划生育科&辅助生殖中心,天津 300211
- Publication Type:Journal Article
- Keywords:
Radiotherapy;
Ovarian reserve;
Fertility;
Abscopal effect;
Primordial follicles
- From:
Chinese Journal of Reproduction and Contraception
2023;43(7):703-712
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect and possible mechanism of the X-ray radiation-induced abscopal effects (X-RIAEs) on the ovarian reserve of mice.Methods:Totally sixteen female C57BL/6J mice aged 6-8 weeks with regular estrous cycle were randomly divided into the sham group ( n=8) and irradiation group ( n=8). After anesthesia, the mice in the irradiation group were irradiated with 8 Gy X-ray on the local area of the chest every day for 3 d, while the mice in the sham group were not irradiated. After irradiation 21 d, the estrous cycle, serum hormones, serum pro-inflammatory factors, and ovarian morphological changes were detected. Ribonucleic acid sequencing (RNA-seq) was used to detect the expression of transcriptional levels in mouse ovarian tissues. The differentially expressed genes (DEGs) were screened and analyzed by gene ontology-biological process (GO_BP). Real-time quantitative polymerase chain reaction (RT-qPCR) verified the sequencing results. The expression and localization of spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein 1 (SOHLH1) and neutrophil elastase (NE) in ovarian tissues were detected by immunohistochemistry (IHC). Results:Compared with mice in the sham group, the irradiation group had a disordered estrous cycle, reduced primordial follicles[10.50 (1.25, 12.75) vs. 60.00 (30.00, 90.25), P<0.001] and growing follicles [(4.50 (2.50, 9.00) vs. 18.50 (18.00, 20.75), P<0.001], significantly increased atretic follicles [56.00 (45.25, 98.75) vs. 12.50 (5.25, 20.25), P<0.001]. The levels of serum estradiol [(70.28±5.27) pmol/L] and anti-Müllerian hormone [(104.00±6.98) μg/L] in the irradiation group were significantly lower than those in the sham group [(97.58±7.25) pmol/L, P=0.016; (129.70±8.39) μg/L, P=0.046], but the follicle-stimulating hormone (FSH) level in the irradiation group was not significantly different from that in the sham group ( P>0.05). Compared with the sham group, the serum levels of TNF-α [(488.30±36.20) μg/L vs. (31.61±12.89) μg/L, P<0.001] and IL-1β [(62.37±2.50) μg/L vs. (52.75±2.06) μg/L, P=0.018] in the irradiation group were significantly increased, and the serum level of interleukin (IL)-6 in the irradiation group was also increased compared with the sham group, but the difference was not statistically significant ( P>0.05). The results of GO_BP analysis showed that the down-regulated DGEs were mainly involved in the process of follicular development, and the up-regulated DGEs were involved in the inflammation process. The results of RT-qPCR were consistent with those of sequencing. The immunohistochemistry results showed that the positive expression area of SOHLH1 in the irradiation group [(23.18±4.00)%] was significantly lower than that of the sham group [(65.90±6.28)%, P=0.005], while the positive expression area of NE [(30.73±4.00)%] was significantly higher than that of the sham group [(14.47±2.22)%, P=0.024]. Conclusion:X-RIAEs can induce an inflammatory reaction in ovarian tissue and inhibit the growth and development of ovarian follicles in mice, which leads to a decrease in ovarian reserve.