Mechanisms of Spermatogenic Dysfunction and Sperm Quality Degradation Induced by Propylthiouracil via Endoplasmic Reticulum Stress in Rats and Interventional Effect of Shugan Bushen Yulin Decoction
10.13422/j.cnki.syfjx.20241639
- VernacularTitle:丙硫氧嘧啶通过内质网应激损害大鼠生精功能和精子质量的机制及疏肝补肾毓麟汤的干预作用
- Author:
Yuhao MENG
1
;
Xiaocui JIANG
2
;
Min XIAO
2
;
Chaoyang WANG
1
Author Information
1. School of Basic Medical Sciences， Hubei University of Chinese Medicine， Wuhan 430065， China
2. Hubei Shizhen Laboratory， Wuhan 430065， China
- Publication Type:Journal Article
- Keywords:
Shugan Bushen Yulin decoction;
propylthiouracil;
endoplasmic reticulum stress;
protein kinase RNA-like endoplasmic reticulum kinase （PERK）/eukaryotic translation initiation factor 2α kinase （EIF2α）/activating transcription factor 4 （ATF4） signaling pathway;
sperm quality
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(9):79-89
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the mechanisms through which Shugan Bushen Yulin decoction ameliorates spermatogenic dysfunction and sperm quality degradation caused by propylthiouracil （PTU） via the endoplasmic reticulum stress pathway in rats. MethodsSixty male rats were randomly assigned into six groups： a control group， a model group， low- （6.75 g·kg-1）， medium- （13.5 g·kg-1）， and high-dose （27 g·kg-1） Shugan Bushen Yulin decoction groups， and an L-carnitine （0.27 g·kg-1） group， with ten rats in each group. Other groups except the control group were administrated with PTU （10 mg·kg-1） by gavage for 12 consecutive days. After the completion of modeling， rats were administrated with corresponding agents or normal saline （control group） via gavage for 28 consecutive days. Twenty-four hours after the last administration， rats were sacrificed， and the body and organ （testis， epididymis， and seminal vesicle） weights were measured to calculate the organ indices. Hematoxylin-eosin staining was employed to observe the pathological changes in the testes and epididymis， and the testicular spermatogenic function of rats was scored. Enzyme-linked immunosorbent assay was employed to measure the levels of thyroid-stimulating hormone （TSH）， triiodothyronine （T3）， thyroxine （T4）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， testosterone （T）， estradiol （E2）， and malondialdehyde （MDA） and the activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in the rat serum. Terminal deoxynucleotidyl transferase dUTP nick end labeling was adopted to assess the rate of testicular cell apoptosis. Western blot was conducted to determine the expression levels of glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， phosphorylated protein kinase RNA-like endoplasmic reticulum kinase （p-PERK）， protein kinase RNA-like endoplasmic reticulum kinase （PERK）， phosphorylated eukaryotic translation initiation factor 2α kinase （p-EIF2α）， eukaryotic translation initiation factor 2α kinase （EIF2α）， and activating transcription factor 4 （ATF4） in the testicular tissue of rats. ResultsCompared with the control group， the model group exhibited reductions in volumes and indexes of testes， epididymides， and seminal vesicles （P<0.01）， pathological damage of testes and epididymides， and declines in spermatogenic function and sperm density and motility （P<0.01）. In addition， the model group demonstrated elevated serum levels of TSH and MDA， lowered levels of T3， T4， FSH， LH， T， and E2， decreased activities of SOD and GSH-Px （P<0.05， P<0.01）， an increased apoptosis rate of testicular cells （P<0.01）， and up-regulated expression of GRP78， CHOP， p-PERK/PERK， p-EIF2α/EIF2α， and ATF4 in the testicular tissue （P<0.01）. Compared with the model group， Shugan Bushen Yulin decoction at different doses improved the morphology and indexes of testes， epididymides， and seminal vesicles （P<0.05）， restored the spermatogenic function （P<0.05， P<0.01）， increased the sperm density and motility （P<0.05， P<0.01）， and decreased the percentage of apoptotic testicular cells （P<0.05）. Furthermore， the decoction lowered the serum level of MDA， elevated the serum levels of FSH， LH， T， and E2， and increased the activities of SOD and GSH-Px （P<0.05， P<0.01）. Moreover， the expression levels of GRP78， CHOP， p-PERK/PERK， p-EIF2α/EIF2α， and ATF4 in the testicular tissue were down-regulated （P<0.05， P<0.01）. ConclusionShugan Bushen Yulin decoction can ameliorate the spermatogenic dysfunction and sperm quality degradation induced by PTU in a rat model of hypothyroidism by repairing the testicular oxidative damage and regulating the PERK/EIF2α/ATF4 signaling pathway， thereby alleviating spermatogenic cell apoptosis.
