Dosage of 4-Vinylcyclohexene Diepoxide in Induction of Premature Ovarian Insufficiency in Rats
10.13422/j.cnki.syfjx.20241005
- VernacularTitle:二氧化乙烯基环己烯致大鼠早发性卵巢功能不全模型的给药剂量探讨
- Author:
Weixin LI
1
;
Pengfei DU
1
;
Yaoyao ZHU
1
;
Chenchen SU
1
;
Huanfang XU
1
;
Li YANG
1
;
Xiaojing SONG
1
;
Yigong FANG
1
Author Information
1. Institute of Acupuncture and Moxibustion，China Academy of Chinese Medical Sciences， Beijing 100700，China
- Publication Type:Journal Article
- Keywords:
4-vinylcyclohexene diepoxide;
premature ovarian insufficiency;
animal model;
dosage study;
pregnancy outcome
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(18):72-79
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo compare the effects of different doses and withdrawal time of 4-vinylcyclohexene diepoxide （VCD） on the reproductive endocrine levels of female rats， and to explore the effective， stable， and safe dosage of VCD for constructing a premature ovarian insufficiency （POI） rat model. MethodSD rats with regular estrous cycles were randomly divided into three groups： blank group， low-dose VCD group （80 mg·kg-1·d-1）， and high-dose VCD group （160 mg·kg-1·d-1）， with 24 rats in each group. After drug intervention， samples were collected on the 15th day （D15） and the 45th day （D45） after intervention. The general condition， rate of estrous cycle disturbance， serum hormone levels， ovarian histomorphology， follicle count， pregnancy outcome， and the protein and mRNA expression of transforming growth factor （TGF）-β and Smad2/3 were assessed. ResultCompared with the blank group， the low-dose VCD group showed no significant differences in the rate of estrous cycle disturbance or serum follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and estradiol （E2） levels. Ovarian tissue was damaged. Specifically， the number of primordial and primary follicles decreased on D15 （P<0.01）， and the number of secondary follicles （P<0.01） and antral follicles （P<0.05） further decreased on D45. The litter number decreased on D15 （P<0.05）， but there was no significant difference on D45. Furthermore， TGF-β protein levels increased on D15 （P<0.05） and D45 （P<0.01）. The Smad2/3 levels increased on D45 （P<0.01）， and TGF-β and Smad2/3 mRNA levels increased on D45 （P<0.05）. Compared with the results in the blank group， the disturbance rate of the estrous cycle increased on D45 in the high-dose VCD group （P<0.01）. The serum of FSH and LH increased （P<0.01）， while E2 decreased （P<0.05）. Ovarian tissue was damaged， and the downward trend of follicles at all levels was similar to that in the low-dose VCD group. The litter number significantly decreased on D15 and D45. TGF-β and Smad2/3 protein levels increased （P<0.05，P<0.01）， and TGF-β mRNA increased on D45 （P<0.05）. ConclusionHigh-dose VCD is an ideal method for constructing a POI rat model， being effective， stable， and safe.
