重金属镉诱导雄性生殖功能损伤的机制

doi:10.3969/j.issn.1006-5725.2024.07.002

Abstract

Abstract:

Cadmium is one of the heavy metals with severe reproductive toxicity， whose half-life lasts 20 to 40 years. Cadmium could induce dysfunction of testis and epididymis for its significant accumulation in human testis， and the amount， motility parameters and morphology of sperm change abnormally. The adverse change could also extend to male offspring and cause the impairment of their reproductive system. There has been no clear mechanism of how cadmium induces dysfunction of male reproductive system， and treatment for the adverse influence on male reproductive system by cadmium has not yet been found. Therefore， this problem has been discussed in reproductive and environmental field for a long time. A number of previous investigations showed that cadmium could damage male fertility by followed pathways， including interfering with hormone secretion， inducing oxidative stress， activating inflammation and apoptosis， and causing energy metabolism disorder， etc. In order to enlighten new ideas for therapeutic targets of male reproductive function damage induced by cadmium， we systematically reviewed and summarized the findings of previous publications in this paper.

Key words: cadmium, reproductive system, testis, epididymis, sperm

CLC Number:

R992

Liantong WANG,Meiqi REN,Liqin WEN,Xiao SHI,Song. QUAN. Mechanisms of male reproductive function damage induced by heavy metal cadmium[J]. The Journal of Practical Medicine, 2024, 40(7): 887-892.

References 48

1	EGGER A E， GRABMANN G， GOLLMANN-TEPEKÖYLÜ C， et al. Chemical imaging and assessment of cadmium distribution in the human body ［J］. Metallomics， 2019， 11（12）： 2010-9. doi:10.1039/c9mt00178f doi: 10.1039/c9mt00178f
2	YANG Q， LI Z， LU X， et al. A review of soil heavy metal pollution from industrial and agricultural regions in China： Pollution and risk assessment ［J］. Sci Total Environ， 2018， 642： 690-700. doi:10.1016/j.scitotenv.2018.06.068 doi: 10.1016/j.scitotenv.2018.06.068
3	GAO Y， HONG J， GUO Y， et al. Assessment spermatogenic cell apoptosis and the transcript levels of metallothionein and p53 in Meretrix meretrix induced by cadmium ［J］. Ecotoxicol Environ Saf， 2021， 217： 112230. doi:10.1016/j.ecoenv.2021.112230 doi: 10.1016/j.ecoenv.2021.112230
4	MARETTOVA E， MARETTA M， LEGATH J. Toxic effects of cadmium on testis of birds and mammals： a review ［J］. Anim Reprod Sci， 2015， 155： 1-10. doi:10.1016/j.anireprosci.2015.01.007 doi: 10.1016/j.anireprosci.2015.01.007
5	ABARIKWU S O， ORUITEMEKA S， UWADILEKE I A， et al. Oral administration of cadmium depletes intratesticular and epididymal iron levels and inhibits lipid peroxidation in the testis and epididymis of adult rats ［J］. J Trace Elem Med Biol， 2018， 48： 213-223. doi:10.1016/j.jtemb.2018.04.011 doi: 10.1016/j.jtemb.2018.04.011
6	LIU D， WAN J， LIU Z， et al. Determination of cadmium induced acute and chronic reproductive toxicity with Raman spectroscopy ［J］. Lasers Med Sci， 2020， 35（9）： 1919-1926. doi:10.1007/s10103-020-02976-6 doi: 10.1007/s10103-020-02976-6
7	FANG Y， XIANG Y， LU X， et al. Epigenetic dysregulation of Mdr1b in the blood-testis barrier contributes to dyszoospermia in mice exposed to cadmium ［J］. Ecotoxicol Environ Saf， 2020， 190： 110142. doi:10.1016/j.ecoenv.2019.110142 doi: 10.1016/j.ecoenv.2019.110142
8	VENDITTI M， RHOUMA M BEN， ROMANO M Z， et al. Evidence of melatonin ameliorative effects on the blood-testis barrier and sperm quality alterations induced by cadmium in the rat testis ［J］. Ecotoxicol Environ Saf， 2021， 226： 112878. doi:10.1016/j.ecoenv.2021.112878 doi: 10.1016/j.ecoenv.2021.112878
9	YU W， XU Z， GAO Q， et al. Protective role of wogonin against cadmium induced testicular toxicity： Involvement of antioxidant， anti-inflammatory and anti-apoptotic pathways ［J］. Life Sci， 2020， 258： 118192. doi:10.1016/j.lfs.2020.118192 doi: 10.1016/j.lfs.2020.118192
10	MOMENI H R， ESKANDARI N. Curcumin protects the testis against cadmium-induced histopathological damages and oxidative stress in mice ［J］. Hum Exp Toxicol， 2020， 39（5）： 653-661. doi:10.1177/0960327119895564 doi: 10.1177/0960327119895564
11	ARAB H H， GAD A M， REDA E， et al. Activation of autophagy by sitagliptin attenuates cadmium-induced testicular impairment in rats： Targeting AMPK/mTOR and Nrf2/HO-1 pathways ［J］. Life Sci， 2021， 269： 119031. doi:10.1016/j.lfs.2021.119031 doi: 10.1016/j.lfs.2021.119031
12	ABDEL LATIF H， ABDEL KHALEK R， ABDELGALIL W， et al. Nanocurcumin versus mesenchymal stem cells in ameliorating the deleterious effects in the cadmium-induced testicular injury： A crosstalk between oxidative and apoptotic markers ［J］. Andrologia， 2020， 52（10）： e13760. doi:10.1111/and.13760 doi: 10.1111/and.13760
13	DUBÉ E， CYR D G. The blood-epididymis barrier and human male fertility ［J］. Adv Exp Med Biol， 2012， 763： 218-236. doi:10.1007/978-1-4614-4711-5_11 doi: 10.1007/978-1-4614-4711-5_11
14	LAMAS C A， CUQUETTO-LEITE L， NASCIMENTO DA SILVA E DO， et al. Grape juice concentrate alleviates epididymis and sperm damage in cadmium-intoxicated rats ［J］. Int J Exp Pathol， 2017， 98（2）： 86-99. doi:10.1111/iep.12227 doi: 10.1111/iep.12227
15	SHI X， FU L. Piceatannol inhibits oxidative stress through modification of Nrf2-signaling pathway in testes and attenuates spermatogenesis and steroidogenesis in rats exposed to cadmium during adulthood ［J］. Drug Des Devel Ther， 2019， 13： 2811-2824. doi:10.2147/dddt.s198444 doi: 10.2147/dddt.s198444
16	AMIRJANNATY S， GASHTI N G， MOJTAHEDI A， et al. An In vitro Study on the Protective Effect of Melatonin on Human Sperm Parameters Treated by Cadmium ［J］. J Hum Reprod Sci， 2022， 15（1）： 21-26. doi:10.4103/jhrs.jhrs_151_21 doi: 10.4103/jhrs.jhrs_151_21
17	WANG L， LI Y， FU J， et al. Cadmium inhibits mouse sperm motility through inducing tyrosine phosphorylation in a specific subset of proteins ［J］. Reprod Toxicol， 2016， 63： 96-106. doi:10.1016/j.reprotox.2016.05.018 doi: 10.1016/j.reprotox.2016.05.018
18	LI R， LUO X， LI L， et al. The Protective Effects of Melatonin Against Oxidative Stress and Inflammation Induced by Acute Cadmium Exposure in Mice Testis ［J］. Biol Trace Elem Res， 2016， 170（1）： 152-164. doi:10.1007/s12011-015-0449-6 doi: 10.1007/s12011-015-0449-6
19	MA D， HOU Y， DU L， et al. Oxidative damages and ultrastructural changes in the sperm of freshwater crab Sinopotamon henanense exposed to cadmium ［J］. Ecotoxicol Environ Saf， 2013， 98： 244-249. doi:10.1016/j.ecoenv.2013.08.004 doi: 10.1016/j.ecoenv.2013.08.004
20	AKINOLA A O， OYEYEMI A W， DARAMOLA O O， et al. Effects of the methanol root extract of Carpolobia lutea on sperm indices， acrosome reaction， and sperm DNA integrity in cadmium-induced reproductive toxicity in male Wistar rats ［J］. JBRA Assist Reprod， 2020， 24（4）： 454-465.
21	SHI X， CHAN C P S， MAN G K Y， et al. Associations between blood metal/ metalloid concentration and human semen quality and sperm function： A cross-sectional study in Hong Kong ［J］. J Trace Elem Med Biol， 2021， 65： 126735. doi:10.1016/j.jtemb.2021.126735 doi: 10.1016/j.jtemb.2021.126735
22	罗英，徐楗荧，林小民，等. 精子DNA碎片率与男性不育及其配偶早期复发性流产的关系［J］. 实用医学杂志， 2021， 37（16）： 2133-2136. doi:10.3969/j.issn.1006-5725.2021.16.020 doi: 10.3969/j.issn.1006-5725.2021.16.020
23	ZHAO X， CHENG Z， ZHU Y I， et al. Effects of paternal cadmium exposure on the sperm quality of male rats and the neurobehavioral system of their offspring ［J］. Exp Ther Med， 2015， 10（6）： 2356-2360. doi:10.3892/etm.2015.2777 doi: 10.3892/etm.2015.2777
24	ZHANG T， GAO X， LUO X， et al. The effects of long-term exposure to low doses of cadmium on the health of the next generation of mice ［J］. Chem Biol Interact， 2019， 312： 108792. doi:10.1016/j.cbi.2019.108792 doi: 10.1016/j.cbi.2019.108792
25	NAN Y， YI S J， ZHU H L， et al. Paternal cadmium exposure increases the susceptibility to diet-induced testicular injury and spermatogenic disorders in mouse offspring ［J］. Chemosphere， 2020， 246： 125776. doi:10.1016/j.chemosphere.2019.125776 doi: 10.1016/j.chemosphere.2019.125776
26	SAINTILNORD W N， TENLEP S Y N， PRESTON J D， et al. Chronic Exposure to Cadmium Induces Differential Methylation in Mice Spermatozoa ［J］. Toxicol Sci， 2021， 180（2）： 262-276. doi:10.1093/toxsci/kfab002 doi: 10.1093/toxsci/kfab002
27	MU Y， HU X， YANG P， et al. The effects of cadmium on the development of Drosophila and its transgenerational inheritance effects ［J］. Toxicology， 2021， 462： 152931. doi:10.1016/j.tox.2021.152931 doi: 10.1016/j.tox.2021.152931
28	PIERRON F， LORIOUX S， HEROIN D， et al. Transgenerational epigenetic sex determination： Environment experienced by female fish affects offspring sex ratio ［J］. Environ Pollut， 2021， 277： 116864. doi:10.1016/j.envpol.2021.116864 doi: 10.1016/j.envpol.2021.116864
29	NNA V U， UJAH G A， MOHAMED M， et al. Cadmium chloride-induced testicular toxicity in male wistar rats； prophylactic effect of quercetin， and assessment of testicular recovery following cadmium chloride withdrawal ［J］. Biomed Pharmacother， 2017， 94： 109-123. doi:10.1016/j.biopha.2017.07.087 doi: 10.1016/j.biopha.2017.07.087
30	YAO Y， WAN Y， SHI X， et al. Letrozole protects against cadmium-induced inhibition of spermatogenesis via LHCGR and Hsd3b6 to activate testosterone synthesis in mice ［J］. Reprod Biol Endocrinol， 2022， 20（1）： 43. doi:10.1186/s12958-022-00915-4 doi: 10.1186/s12958-022-00915-4
31	FANG Y， ZHANG L， DONG X， et al. Downregulation of vdac2 inhibits spermatogenesis via JNK and P53 signalling in mice exposed to cadmium ［J］. Toxicol Lett， 2020， 326： 114-122. doi:10.1016/j.toxlet.2020.03.011 doi: 10.1016/j.toxlet.2020.03.011
32	文艺，杨强震，李思思，等. NAC抑制镉离子诱导的小鼠精子DLD酪氨酸磷酸化作用［J］. 上海交通大学学报（农业科学版）， 2019，37（2）： 37-46.
33	刘居理，陈胜辉，李琳，等. 精子膜及线粒体活性氧对男性生育力的影响及其在辅助生殖技术中的应用［J］. 实用医学杂志， 2023， 39（21）： 2704-2708. doi:10.3969/j.issn.1006-5725.2023.21.003 doi: 10.3969/j.issn.1006-5725.2023.21.003
34	BASHIR N， SHAGIRTHA K， MANOHARAN V， et al. The molecular and biochemical insight view of grape seed proanthocyanidins in ameliorating cadmium-induced testes-toxicity in rat model： implication of PI3K/Akt/Nrf-2 signaling ［J］. Biosci Rep， 2019， 39（1）：BSR20180515. doi:10.1042/bsr20180515 doi: 10.1042/bsr20180515
35	ZHOU J， ZENG L， ZHANG Y， et al. Cadmium exposure induces pyroptosis in testicular tissue by increasing oxidative stress and activating the AIM2 inflammasome pathway ［J］. Sci Total Environ， 2022， 847： 157500. doi:10.1016/j.scitotenv.2022.157500 doi: 10.1016/j.scitotenv.2022.157500
36	MANCUSO F， ARATO I， BELLUCCI C， et al. Zinc restores functionality in porcine prepubertal Sertoli cells exposed to subtoxic cadmium concentration via regulating the Nrf2 signaling pathway ［J］. Front Endocrinol （Lausanne）， 2023， 14： 962519. doi:10.3389/fendo.2023.962519 doi: 10.3389/fendo.2023.962519
37	WANG Y， WU J， ZHANG M， et al. Cadmium exposure during puberty damages testicular development and spermatogenesis via ferroptosis caused by intracellular iron overload and oxidative stress in mice ［J］. Environ Pollut， 2023， 325： 121434. doi:10.1016/j.envpol.2023.121434 doi: 10.1016/j.envpol.2023.121434
38	WANG M， WANG X F， LI Y M， et al. Cross-talk between autophagy and apoptosis regulates testicular injury/recovery induced by cadmium via PI3K with mTOR-independent pathway ［J］. Cell Death Dis， 2020， 11（1）： 46. doi:10.1038/s41419-020-2246-1 doi: 10.1038/s41419-020-2246-1
39	JI Y L， WANG H， ZHAO X F， et al. Crosstalk between endoplasmic reticulum stress and mitochondrial pathway mediates cadmium-induced germ cell apoptosis in testes ［J］. Toxicol Sci， 2011， 124（2）： 446-459. doi:10.1093/toxsci/kfr232 doi: 10.1093/toxsci/kfr232
40	WANG S， REN X， HU X， et al. Cadmium-induced apoptosis through reactive oxygen species-mediated mitochondrial oxidative stress and the JNK signaling pathway in TM3 cells， a model of mouse Leydig cells ［J］. Toxicol Appl Pharmacol， 2019， 368： 37-48. doi:10.1016/j.taap.2019.02.012 doi: 10.1016/j.taap.2019.02.012
41	YI L， SHANG X J， LV L， et al. Cadmium-induced apoptosis of Leydig cells is mediated by excessive mitochondrial fission and inhibition of mitophagy ［J］. Cell Death Dis， 2022， 13（11）： 928. doi:10.1038/s41419-022-05364-w doi: 10.1038/s41419-022-05364-w
42	LEE S W， KIM B， SEONG J B， et al. ATF6 is a critical regulator of cadmium-mediated apoptosis in spermatocytes ［J］. Toxicol Sci， 2023， 194（2）： 167-177. doi:10.1093/toxsci/kfad055 doi: 10.1093/toxsci/kfad055
43	FOUAD A A， ABDEL-AZIZ A M， HAMOUDA A A H. Diacerein Downregulates NLRP3/Caspase-1/IL-1beta and IL-6/STAT3 Pathways of Inflammation and Apoptosis in a Rat Model of Cadmium Testicular Toxicity ［J］. Biol Trace Elem Res， 2020， 195（2）： 499-505. doi:10.1007/s12011-019-01865-6 doi: 10.1007/s12011-019-01865-6
44	SADASIVAM M， RAMATCHANDIRIN B， BALAKRISHNAN S， et al. TNF-α-mediated suppression of Leydig cell steroidogenesis involves DAX-1 ［J］. Inflamm Res， 2015， 64（7）： 549-556. doi:10.1007/s00011-015-0835-8 doi: 10.1007/s00011-015-0835-8
45	FOUAD A A， JRESAT I. Captopril and telmisartan treatments attenuate cadmium-induced testicular toxicity in rats ［J］. Fundam Clin Pharmacol， 2013， 27（2）： 152-160. doi:10.1111/j.1472-8206.2011.00974.x doi: 10.1111/j.1472-8206.2011.00974.x
46	GUNNARSSON D， SVENSSON M， SELSTAM G， et al. Pronounced induction of testicular PGF（2 alpha） and suppression of testosterone by cadmium-prevention by zinc ［J］. Toxicology， 2004， 200（1）： 49-58. doi:10.1016/j.tox.2004.03.003 doi: 10.1016/j.tox.2004.03.003
47	DONG W， ZHANG K， LIU G， et al. Puerarin prevents cadmium-induced disorder of testicular lactic acid metabolism in rats by activating 5' AMP-activated protein kinase （AMPK）/sirtuin 1 （SIRT1） signaling pathway ［J］. Environ Toxicol， 2021， 36（5）： 945-957. doi:10.1002/tox.23096 doi: 10.1002/tox.23096
48	COSTA R DA， BOTANA D， PINERO S， et al. Cadmium inhibits motility， activities of plasma membrane Ca（2+）-ATPase and axonemal dynein-ATPase of human spermatozoa ［J］. Andrologia， 2016， 48（4）： 464-469. doi:10.1111/and.12466 doi: 10.1111/and.12466

[1]	Xi HU,Yan LI,Yang. LIU. Recent advances on the application of deep learning in assisted reproductive technology [J]. The Journal of Practical Medicine, 2024, 40(7): 893-897.
[2]	Bing′er WU,Qing LI,Kerong YANG,Jian ZHANG,Yi YU,Lei LEI,Bo. HU. Impact of spermidine on proliferation and apoptosis in diffuse large B⁃cell lymphoma cell lines [J]. The Journal of Practical Medicine, 2024, 40(22): 3130-3137.
[3]	Dechao LI,Mingjin ZHANG,Yibi LAN,Chunlei MA,Weijin. FU. Expression of allograft inflammatory factor⁃1 in the testicular model of diabetes mellitus rats [J]. The Journal of Practical Medicine, 2024, 40(1): 65-71.
[4]	Juli LIU,Shenghui CHEN,Lin LI,Wenliang YAO,Lijuan YANG,Yanwen RAO. Effects of sperm membrane and mitochondrial reactive oxygen species on male fertility and its application in assisted reproductive technology [J]. The Journal of Practical Medicine, 2023, 39(21): 2704-2708.
[5]	LUO Yang, PENG Fang, LI Lei, LIU Wenbo, LIU Hanyan.. Effects of assisted oocyte activation with ionomycin in thepatients with previous fertilization failure after ICSI [J]. The Journal of Practical Medicine, 2022, 38(9): 1060-1069.
[6]	WU Shenghao, HU Yangyang, LIU Xiaoming.. A comparison of pregnancy and neonatal outcomes in patients with obstructive azoospermia after fresh ver⁃ sus frozen ⁃ thawed blastocyst transfer [J]. The Journal of Practical Medicine, 2022, 38(9): 1065-1069.
[7]	WANG Ming, SA Rula, WANG Chaoqi, YAN Zhen.. miR ⁃let ⁃7c improves sperm quality mediating differentiation of spermatogonial stem cell in mice [J]. The Journal of Practical Medicine, 2022, 38(20): 2524-2530.
[8]	ZHAO Yinyin, QIU Xianxian, XIAO Yuehai, JIANG Kehua, LUO Dajin, SUN Fa. . Research progress of the influence of PM2.5 on male reproductive system [J]. The Journal of Practical Medicine, 2021, 37(9): 1222-1226.
[9]	ZHANG Chunlei, DING Haoshuai, KANG Yafen, MENG Dongdong, XU Dongbo, YANG Qi, ZHOU Fenghai, CHANG Dehui. . Respective and joint values of mycobacterium tuberculosis⁃specific cellular immunity test and tuberculosis antibody test in diagnosis of male genital system tuberculosis [J]. The Journal of Practical Medicine, 2021, 37(20): 2670-2674.
[10]	LIANG Jiaying, ZENG Weihong, ZHANG Jie, LAI Youxing, HUANG Zhicheng, ZHENG Yichun.. Heterogeneous Nuclear Ribonucleoprotein U expression in patients with severe oligoasthenospermia and its effect on clinical outcome of intracytoplasmic sperm injection [J]. The Journal of Practical Medicine, 2021, 37(19): 2468-2472.
[11]	FAN Xiaomeng, ZHU Hongwei, ZHU Zhimin, QIU Aiping, LIU Yongsheng. . Clinical application value of highly selective spermatic vein ligation under the outer ring microscope [J]. The Journal of Practical Medicine, 2021, 37(16): 2124-2128.
[12]	LUO Ying, XU Jianying, LIN Xiaomin, JIN Long, QU Shihao.. Correlation between sperm DNA fragmentation index and male infertility or early recurrent abortion occurred in the subjects′ spouses [J]. The Journal of Practical Medicine, 2021, 37(16): 2133-2136.
[13]	SUN Xian, JIANG Hong, LIU Yingchun, NI Feng, ZHU Jie. . R711.6 Clinical application value of oocyte vitrification [J]. The Journal of Practical Medicine, 2021, 37(11): 1423-1427.

Mechanisms of male reproductive function damage induced by heavy metal cadmium

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References 48

Related Articles 13

Recommended Articles

Metrics

Comments