Effect of different doses of quinestrol on organs, sperm density, reproductive hormones and CYP3A4 enzyme levels of male and female mice

WANG Yujie; LIU Yuhang; QIN Jiao; LIU Yutong; NIE Haiyan; LIU Quansheng

doi:10.16829/j.slxb.150441

2021 , Vol. 41 >Issue 2: 202 - 213

DOI: https://doi.org/10.16829/j.slxb.150441

ORIGINAL PAPERS

Effect of different doses of quinestrol on organs, sperm density, reproductive hormones and CYP3A4 enzyme levels of male and female mice

WANG Yujie ,
LIU Yuhang ,
QIN Jiao ,
LIU Yutong ,
NIE Haiyan ,
LIU Quansheng

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1 College of Life Science and Technology, Central South University of Forestry and Technology, Changsha 410004, China;
2 Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou 510260, China;
3 College of Agriculture, South China Agriculture University, Guangzhou 510642, China

Received date: 2020-05-23

Online published: 2021-04-02

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Abstract

To investigate the effects of varied-dose quinestrol on the weight of organs,concentration of reproductive hormones in serum,and content of CYP3A4 enzyme in intestine and liver,Swiss mice were treated with 0.008 mg/kg,0.04 mg/kg,0.2 mg/kg,1.0 mg/kg,and 5.0 mg/kg of quinestrol for 3 consecutive days and dissected on the day 7 after the first dose.In female mice,the liver weight increased with the dose increasing,and the liver weight of mice in the dose of 5.0 mg/kg increased 89.7% than that of the control.Small intestine,kidney and spleen were changed significantly,but there was no evident dose effect.The uterus showed different degrees of edema in female mice treated by 0.2 mg/kg,1.0 mg/kg,and 5.0 mg/kg of quinestrol.The luteinizing hormone and estradiol concentrations in serum were no significant change among varied groups of female mice.However,the follicle-stimulating hormone concentration significantly increased in female mice treated with 1.0 mg/kg quinestrol compared with the control.CYP3A4 enzyme content of liver in female treated by 1.0 mg/kg and 5.0 mg/kg of quinestrol increased significantly by 59.1% and 102.9%,respectively.In male mice,quinestrol at different doses showed a significant impact on the liver and spleen,which increased by 23.3% and 130% in mice treated by 5.0 mg/kg of quinestrol,but no significant change was observed in small intestine and kidney.Quinestrol had no significant dose effect on testes,however epididymis decreased significantly in male treated with 5.0 mg/kg quinestrol.Sperm density and total sperm count decreased by 43.9% and 70.5% at the dose of 1.0 mg/kg and 5.0 mg/kg compared with the control male,respectively.Luteinizing hormone and testosterone concentration in serum decreased significantly in high dosage groups.CYP3A4 content in per g tissues and total content in liver increased by 7.1% and 30% in male treated with 5 mg/kg quinestrol,respectively.In conclusion,quinestrol has inhibitory effects on reproduction of male and female mice,but the effective dose on female is lower than male.The response of liver and CYP3A4 to quinestrol in female was more sensitive than that in male,which indicated more quickly metabolism speed to quinestrol in female mice.

Key words： CYP3A4; Fertility control; Hormone; Mice; Quinestrol

Cite this article

WANG Yujie , LIU Yuhang , QIN Jiao , LIU Yutong , NIE Haiyan , LIU Quansheng . Effect of different doses of quinestrol on organs, sperm density, reproductive hormones and CYP3A4 enzyme levels of male and female mice[J]. ACTA THERIOLOGICA SINICA, 2021 , 41(2) : 202 -213 . DOI: 10.16829/j.slxb.150441

References

Amory J K,Page S T,Bremner W J.2006.Drug insight:recent advances in male hormonal contraception.Nature Clinical Practice Endocrinology & Metabolism,2(1):32-41.
Barka T,Popper H.1967.Liver enlargement and drug toxicity.Medicine,46(2):103-117.
Brooks J E,Bowerman A M.1971.Estrogenic steroid used to inhibit reproduction in wild Norway rats.Journal of Wildlife Management,35(3):444-449.
Chen Y,Su Q Q,Liu Q S.2017.Effects of quinestrol on the vocal behavior of mice during courtship interactions.Physiology & Behavior,173:216-222.
Cheng N Z,Shu Y,Liu Z Q,Wang L S,Ou Yang D S,Zhou H H.2000.Role of cytochrome P450 in estradiol metabolism in vitro.Acta Pharmacologica Sinica,22(2):148-154.
Ennis B,Stumpf W.1988.Differential induction of progestin-binding sites in uterine cell types by estrogen and antiestrogen.Endocrinology,123(4):1747-1753.
Farber E,Segaloff A.1955.Effect of androgens and growth and other hormones on ethionine fatty liver in rats.The Journal of Biological Chemistry,216(2):471-478.
Giannina T,Meli A.1969.Prolonged oestrogenic activity in rats after single oral administration of ethinyloestradiol-3-cyclopentyl ether.Journal of Pharmacy and Pharmacology,21(4):271-272.
Gioia I A,Lencioni L J,Koch O R.1978.Effects of quinestrol on hepatic function in the rat.Contraception,18(3):277-286.
Gioia I A,Lencioni L J,Tozzini R.1975.The effect of quinestrol on fertility,estrous cycle and endocrine glands in the rat.International Journal of Fertility,20(4):239-244.
Hammond D K,Zhu B T,Wang M Y,Ricci M J,Liehr J G.1997.Cytochrome P450 metabolism of estradiol in hamster liver and kidney.Toxicology and Applied Pharmacology,145(1):54-60.
Hayes F J,Seminara S B,Suzzunne D,Boepple P A,Crowley W F.2000.Aromatase inhibition in the human male reveals a hypothalamic site of estrogen feedback.The Journal of Clinical Endocrinology & Metabolism,85(9):3027-3035.
Hrycay E G,Bandiera S M.2015.Monooxygenase,Peroxidase and Peroxygenase Properties and Mechanisms of Cytochrome P450.Advances in Experimental Medicine and Biology.Springer International Publishing,Switzerland.
Huo X F,Wang D,Liang H C,Shi D Z,Zhang H Q,Liang J J.2006.A preliminary study on the anti-fertility effect of two sterilants to clawed jirds(Meriones unguiculatus).Acta Agrestia Sinica,14(2):184-187.(in Chinese)
Kazi A,Koos R.2007.Estrogen-induced activation of hypoxia-inducible factor-1α,vascular endothelial growth factor expression,and edema in the uterus are mediated by the phosphatidylinositol 3-kinase/Akt pathway.Endocrinology,148(5):2363-2374.
Kunz W,Schaude G,Schmid W,Siess M.1966.Stimulation of liver growth by drugs.I.Morphological analysis.Proceedings of the European Society for the Study of Drug Toxicity,7:113-137.
Li J,Chen F N,Chen Y X,Wang Z X,Dong Y L,Cao J,Si L F,Liu Z J,Zhao Z Q.2017.The study of protection of folacin against quinestrol induced reproductive toxicity in male rat.Acta Veterinaria et Zootechnica Sinica,48(2):351-358.(in Chinese)
Li J,Chen F N,Li C,Chen Y X.2014.Quinestrol induces sperma-togenic apoptosis in vivo via increasing pro-apoptotic proteins in adult male mice.Tissue and Cell,46(5):318-325.
Li J,Chen Y X,Chen F N,Wang Z X,Cao J,Dong Y L,Chen S L.2015.Effects of quinestrol on number and distribution of mast cells in epididymis and gonad in mice.Progress in Veterinary Medicine,36(12):94-97.(in Chinese)
Liu M,Luo R,Wang H,Cao G,Wang Y.2017.Recovery of fertility in quinestrol-treated or diethylstilbestrol-treated mice:implications for rodent management.Integrative Zoology,12(3):250-259.
Liu M,Qu J P,Yang M,Wang Z L,Wang Y L,Zhang Y M,Zhang Z B.2012.Effects of quinestrol and levonorgestrel on populations of plateau pikas,Ochotona curzoniae,in the Qinghai-Tibetan Plateau.Pest Management Science,68(4):592-601.
Liu M,Wan X R,Yin Y M,Li Y X,Sun F,Zhang Z B,Yang H X.2012.Subfertile effects of quinestrol and levonorgestrel in male rats.Reproduction,Fertility and Development,24(2):297-308.
Liu Q S,Qin J,Chen Q,Wang D,Shi D Z.2013.Fertility control of Rattus nitidus using quinestrol:effects on reproductive organs and social behavior.Integrative Zoology,8(S1):9-17.
Lv X H,Shi D Z.2011.The effects of quinestrol as a contraceptive in mongolian gerbils(Meriones unguiculatus).Experimental Animals,60(5):489-496.
Massawe A W,Makundi R H,Zhang Z B,Mhamphi G,Liu M,Li H J,Belmain S R.2018.Effect of synthetic hormones on reproduction in Mastomys natalensis.Journal of Pest Science,91(1):157-168.
Meli A,Steinetz B G,Beach V L,Wolff A,Giannina T.1965.Biological and chromatographic evidence for the storage of ethynylestradiol-3-cyclopentyl ether in rat brain.Experimental Biology and Medicine,119(3):602-606.
Meli A.1963.The mechanism by which 3-etherification with cyclopentyl alcohol enhances the oral activity of ethynylestradiol.Steroids,2(4):417-424.
Mischler T W,Gawlak D.1970.The biological profile of 8-aza quinestrol.Journal of Reproduction and Fertility,22(1):49-56.
Mischler T W,Welaj P,Nemith P.1971.Biological evaluation of two estrogenic steroids as possible rodent chemosterilants.Journal of Wildlife Management,35(3):449-454.
O'Donnell L,Robertson K M,Jones M E,Simpson E R.2001.Estrogen and spermatogenesis.Endocrine Reviews,22(3):289-318.
Qin J,Liu Q S,Shu J,Guo M F.2011.Palatability of anti-fertility baits containing quinestrol and mifepristone on Rattus losea.Guangdong Agricultural Sciences,38(20):84-86.(in Chinese)
Rivera R,Yacobson I,Grimes D.1999.The mechanism of action of hormonal contraceptives and intrauterine contraceptive devices.American Journal of Obstetrics and Gynecology,181(5):1263-1269.
Rockwell L C,Pillai S,Olson C E,Koos R D.2002.Inhibition of vascular endothelial growth factor/vascular permeability factor action blocks estrogen-induced uterine edema and implantation in rodents.Biology of Reproduction,67(6):1804-1810.
Rubin B L,Dorfman A S,Black L,Dorfman R I.1951.Bioassay of estrogens using the mouse uterine response.Endocrinology,49(4):429-439.
Shanghai First Medical College Pharmacology Research Group.1978.Pharmacological effects of oral long-acting contraceptive compound quinestrol bulletin.New Medicine,9(5):233-234.(in Chinese)
Shen W,Guo Y W,Shi D Z,Wang D,Hai S Z.2011.Anti-fertility effect of quinestrol in male Mongolian gerbils(Meriones unguiculatus) and its reversibility.Acta Theriologica Sinica,31(2):171-178.(in Chinese)
Shen W,Shi D Z,Wang D,Guo Y W.2012.Inhibitive effects of quinestrol on male testes in Mongolian gerbils(Meriones unguiculatus).Research in Veterinary Science,93(2):907-913.
Shi Y H,Wang B S,Sun H,Ji Z H,Wang Z L.2018.Effects of levonorgestrel and quinestrol on reproduction of Brandt's voles.Journal of Henan Agricultural Sciences,47(3):82-86.(in Chinese)
Sissan M A G,Menon V P,Leelamma S.1995.Effects of low-dose oral contraceptive oestrogen and progestin on lipid peroxidation in rats.Journal of International Medical Research,23(4):272-278.
Su Q Q,Chen Y,Qin J,Li H J,Liu M,Zhang Z B,Liu Q S.2019.Ratio-dependent effects of quinestrol and levonorgestrel compounds(EP-1) on reproductive parameters of adult male Swiss mice.Pesticide Biochemistry and Physiology,160:181-186.
Su Q Q,Chen Y,Qin J,Wang T L,Wang D H,Liu Q S.2016.Effects of mifepristone and quinestrol on the fertility of female Brandt's voles(Lasiopodomys brandtii) in different reproductive phases.Animal Biology,66(2):133-143.
Su Q Q,Chen Y,Qin J,Wang T L,Wang D H,Liu Q S.2017.Responses in reproductive organs,steroid hormones and CYP450 enzymes in female Mongolian gerbil(Meriones unguiculatus) over time after quinestrol treatment.Pesticide Biochemistry and Physiology,143:122-126.
Van Waterschoot R,Lagas J,Wagenaar E,Van der Kruijssen,Van Herwaarden A,Song J Y,Rooswinkel R,Van Tellingen O,Rosing H,Beijene J,Schinkel A.2009.Absence of both cytochrome P450 3A and P-glycoprotein dramatically increases docetaxel oral bioavailability and risk of intestinal toxicity.Cancer Research,69(23):8996-9002.
Wang D W,Li N,Liu M,Huang B H,Liu Q,Liu X H.2011.Behavioral evaluation of quinestrol as a sterilant in male Brandt's voles.Physiology & Behavior,104(5):1024-1030.
Wang H,Shao Y Y,Chen S,Ping X T,Pan Q,Zhao M R,Qian J.2016.Research progress of quinestrol.Journal of Zhejiang University of Technology,44(1):84-87.(in Chinese)
Wang T T,Guo Y W,Wang D,Hai S Z.2015.Suppression effects of quinestrol on the reproduction of Brandt's voles(Lasiopodomys brandtii).Acta Theriologica Sinica,35(1):87-94.(in Chinese)
Yang J R,Wang Y,Zhang M W,Jiang L F,Shi J,Liu J,Hasibaolidao,Liu Z X.2018.Effect of quinestrol on the reproduction of Meriones unguriculataus in the farming-pastoral transitional zone of Inner Mongolia.Sichuan Journal of Zoology,37(2):207-210.(in Chinese)
Yuan Z P,Tong S M.1985.Morphologic changes in rat endometrium and liver following the administration of a long-acting oral contraceptive-quinestrol.Reproduction & contraception,5(2):22-25.(in Chinese)
Zhang Z B.2000.Mathematical models of wildlife management by contraception.Ecological Modelling,132(1):105-113.
Zhang Z B.2015.A review on anti-fertility effects of levonorgestrel and quinestrol(EP-1) compounds and its components on small rodents.Acta Theriologica Sinica,35(2):203-210.(in Chinese)
Zhao M R,Liu M,Li D,Wan X R,Hinds L A,Wang Y L,Zhang Z B.2007.Anti-fertility effect of levonorgestrel and quinestrol in Brandt's voles(Lasiopodomys brandtii).Integrative Zoology,2(4):260-268.
Zhou X J,Yang Y C,Wang Y,Zhang M W,Li B,Peng Z.2015.The effect of levonorgestrel-quinestrol on female fertility in Microtus fortis.Acta Theriologica Sinica,35(2):176-183.(in Chinese)
上海第一医学院药理学教研室.1978.口服长效避孕药复方炔雌醚的药理作用简报.新医学,9(5):233-234.
王涛涛,郭永旺,王登,海淑珍.2015.炔雌醚对布氏田鼠繁殖的抑制效果.兽类学报,35(1):87-94.
王鸿,邵燕燕,陈苏,平夏婷,潘秋,赵美蓉,钱捷.2016.炔雌醚的研究进展.浙江工业大学学报,44(1):84-87.
李健,陈福宁,陈耀星,王子旭,董玉兰,曹静,司丽芳,刘志军,赵战勤.2017.叶酸对炔雌醚致雄性大鼠生殖损伤的保护作用研究.畜牧兽医学报,48(2):351-358.
李健,陈耀星,陈福宁,王子旭,曹静,董玉兰,陈树林.2015.炔雌醚对小鼠附睾与副性腺肥大细胞数量和分布的影响.动物医学进展,36(12):94-97.
杨进荣,王勇,张美文,姜路帆,师军,刘锦,哈斯宝力道,刘志霄.2018.炔雌醚对内蒙古农牧交错带长爪沙鼠种群繁殖的影响.四川动物,37(2):207-210.
沈伟,郭永旺,施大钊,王登,海淑珍.2011.炔雌醚对雄性长爪沙鼠不育效果及其可逆性.兽类学报,31(2):171-178.
张知彬.2015.左炔诺孕酮和炔雌醚复合物(EP-1) 及组分对鼠类不育效果的研究进展.兽类学报,35(2):203-210.
周训军,杨玉超,王勇,张美文,李波,彭真.2015.左炔诺孕酮和炔雌醚复合不育剂(EP-1) 对雌性东方田鼠生殖的影响.兽类学报,35(2):176-183.
施玉华,王白石,孙红,季志鸿,王振龙.2018.左炔诺孕酮和炔雌醚对布氏田鼠繁殖的影响.河南农业科学,47(3):82-86.
秦姣,刘全生,舒骏,郭明昉.2011.两种不育剂药饵对黄毛鼠的适口性比较.广东农业科学,38(20):84-86.
袁治平,童夙明.1985.长效避孕药炔雌醚对大白鼠子宫内膜和肝脏的形态学影响.生殖与避孕,5(2):22-25.
霍秀芳,王登,梁红春,施大钊,张焕强,梁继军.2006.两种不育剂对长爪沙鼠的作用.草地学报,14(2):184-187.

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