Effects of maternal acrolein exposure during pregnancy on testicular testosterone production in fetal rats

Yang,Yuzhuo; Zhang,Zhe; Zhang,Hongliang; Hong,Kai; Tang,Wenhao; Zhao,Lianming; Lin,Haocheng; Liu,Defeng; Mao,Jiaming; Wu,Han; Jiang,Hui

doi:10.3892/mmr.2017.6624

Effects of maternal acrolein exposure during pregnancy on testicular testosterone production in fetal rats

Authors:
- Yuzhuo Yang
- Zhe Zhang
- Hongliang Zhang
- Kai Hong
- Wenhao Tang
- Lianming Zhao
- Haocheng Lin
- Defeng Liu
- Jiaming Mao
- Han Wu
- Hui Jiang
View Affiliations

Affiliations: Department of Urology, Peking University Third Hospital, Beijing 100191, P.R. China, Reproductive Medicine Center, Peking University Third Hospital, Beijing 100191, P.R. China
Published online on: May 25, 2017 https://doi.org/10.3892/mmr.2017.6624
Pages: 491-498
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Acrolein has been reported to have diverse toxic effects on various organs, including the reproductive system. However, little is known regarding the effects of maternal acrolein exposure on testicular steroidogenesis in male offspring. The present study investigated the effects of acrolein on fetal testosterone production and associated genes. Pregnant Sprague‑Dawley rats were intraperitoneally injected with vehicle (normal saline) or 1, 2 or 5 mg/kg acrolein from gestational day (GD) 14‑20, and fetal testes were examined on GD 21. Fetal body and testicular weights were markedly reduced in pups following exposure to high doses of acrolein (5 mg/kg) in late pregnancy. Notably, in utero exposure of 5 mg/kg acrolein significantly decreased the testicular testosterone level and downregulated the expression levels of steroidogenic acute regulatory protein (StAR) and 3β‑hydroxysteroid dehydrogenase (3β‑HSD), whereas the levels of other steroidogenic enzymes, including scavenger receptor class B, cholesterol side‑chain cleavage enzyme and steroid 17 alpha‑hydroxylase/17,20 lyase, were unaffected. Furthermore, the 3β‑HSD immunoreactive area in the interstitial region of the fetal testes was reduced at a 5 mg/kg dose, whereas the protein expression levels of 4‑hydroxynonenalwere dose‑dependently increased following maternal exposure to acrolein. mRNA expression levels of insulin‑like factor 3, a critical gene involved in testicular descent, were unaltered following maternal acrolein exposure. Taken together, the results of the present study suggested that maternal exposure to high doses of acrolein inhibited fetal testosterone synthesis, and abnormal expression of StAR and 3β‑HSD may be associated with impairment of the steroidogenic capacity.

View Figures

View References

1	Skakkebaek NE, Rajpert-De Meyts E and Main KM: Testicular dysgenesis syndrome: An increasingly common developmental disorder with environmental aspects. Hum Reprod. 16:972–978. 2001. View Article : Google Scholar : PubMed/NCBI
2	Schnack TH, Poulsen G, Myrup C, Wohlfahrt J and Melbye M: Familial coaggregation of cryptorchidism, hypospadias, and testicular germ cell cancer: A nationwide cohort study. J Natl Cancer Inst. 102:187–192. 2010. View Article : Google Scholar : PubMed/NCBI
3	Sharpe RM and Skakkebaek NE: Testicular dysgenesis syndrome: Mechanistic insights and potential new downstream effects. Fertil Steril. 89:(2 Suppl). e33–e38. 2008. View Article : Google Scholar : PubMed/NCBI
4	Macleod DJ, Sharpe RM, Welsh M, Fisken M, Scott HM, Hutchison GR, Drake AJ and van den Driesche S: Androgen action in the masculinization programming window and development of male reproductive organs. Int J Androl. 33:279–287. 2010. View Article : Google Scholar : PubMed/NCBI
5	Liu D, Shen L, Tao Y, Kuang Y, Cai L, Wang D, He M, Tong X, Zhou S, Sun J, et al: Alterations in gene expression during sexual differentiation in androgen receptor knockout mice induced by environmental endocrine disruptors. Int J Mol Med. 35:399–404. 2015.PubMed/NCBI
6	Araki A, Mitsui T, Miyashita C, Nakajima T, Naito H, Ito S, Sasaki S, Cho K, Ikeno T, Nonomura K and Kishi R: Association between maternal exposure to di (2-ethylhexyl) phthalate and reproductive hormone levels in fetal blood: The Hokkaido study on environment and children's health. PLoS One. 9:e1090392014. View Article : Google Scholar : PubMed/NCBI
7	Wilson VS, Lambright CR, Furr JR, Howdeshell KL and Gray Earl L Jr: The herbicide linuron reduces testosterone production from the fetal rat testis during both in utero and in vitro exposures. Toxicol Lett. 186:73–77. 2009. View Article : Google Scholar : PubMed/NCBI
8	Stevens JF and Maier CS: Acrolein: Sources, metabolism, and biomolecular interactions relevant to human health and disease. Mol Nutr Food Res. 52:7–25. 2008. View Article : Google Scholar : PubMed/NCBI
9	Cahill TM: Ambient acrolein concentrations in coastal, remote, and urban regions in California. Environ Sci Technol. 48:8507–8513. 2014. View Article : Google Scholar : PubMed/NCBI
10	Logue JM, Price PN, Sherman MH and Singer BC: A method to estimate the chronic health impact of air pollutants in U.S. residences. Environ Health Perspect. 120:216–222. 2012. View Article : Google Scholar : PubMed/NCBI
11	Moghe A, Ghare S, Lamoreau B, Mohammad M, Barve S, McClain C and Joshi-Barve S: Molecular mechanisms of acrolein toxicity: Relevance to human disease. Toxicol Sci. 143:242–255. 2015. View Article : Google Scholar : PubMed/NCBI
12	DeJarnett N, Conklin DJ, Riggs DW, Myers JA, O'Toole TE, Hamzeh I, Wagner S, Chugh A, Ramos KS, Srivastava S, et al: Acrolein exposure is associated with increased cardiovascular disease risk. J Am Heart Assoc. 3:pii: e000934. 2014. View Article : Google Scholar : PubMed/NCBI
13	Lovell MA, Xie C and Markesbery WR: Acrolein is increased in Alzheimer's disease brain and is toxic to primary hippocampal cultures. Neurobiol Aging. 22:187–194. 2001. View Article : Google Scholar : PubMed/NCBI
14	Golla U, Bandi G and Tomar RS: Molecular cytotoxicity mechanisms of allyl alcohol (acrolein) in budding yeast. Chem Res Toxicol. 28:1246–1264. 2015. View Article : Google Scholar : PubMed/NCBI
15	Slott VL and Hales BF: The embryolethality and teratogenicity of acrolein in cultured rat embryos. Teratology. 34:155–163. 1986. View Article : Google Scholar : PubMed/NCBI
16	Kenney LB, Laufer MR, Grant FD, Grier H and Diller L: High risk of infertility and long term gonadal damage in males treated with high dose cyclophosphamide for sarcoma during childhood. Cancer. 91:613–621. 2001. View Article : Google Scholar : PubMed/NCBI
17	Westlind A, Malmebo S, Johansson I, Otter C, Andersson TB, Ingelman-Sundberg M and Oscarson M: Cloning and tissue distribution of a novel human cytochrome p450 of the CYP3A subfamily, CYP3A43. Biochem Biophys Res Commun. 281:1349–1355. 2001. View Article : Google Scholar : PubMed/NCBI
18	Ekhart C, Doodeman VD, Rodenhuis S, Smits PH, Beijnen JH and Huitema AD: Influence of polymorphisms of drug metabolizing enzymes (CYP2B6, CYP2C9, CYP2C19, CYP3A4, CYP3A5, GSTA1, GSTP1, ALDH1A1 and ALDH3A1) on the pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide. Pharmacogenet Genomics. 18:515–523. 2008. View Article : Google Scholar : PubMed/NCBI
19	Ji YL, Wang H, Liu P, Zhao XF, Zhang Y, Wang Q, Zhang H, Zhang C, Duan ZH, Meng C and Xu DX: Effects of maternal cadmium exposure during late pregnant period on testicular steroidogenesis in male offspring. Toxicol Lett. 205:69–78. 2011. View Article : Google Scholar : PubMed/NCBI
20	Auerbach SS, Mahler J, Travlos GS and Irwin RD: A comparative 90-day toxicity study of allyl acetate, allyl alcohol and acrolein. Toxicology. 253:79–88. 2008. View Article : Google Scholar : PubMed/NCBI
21	Rashedinia M, Lari P, Abnous K and Hosseinzadeh H: Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity. Toxicol Appl Pharmacol. 272:199–207. 2013. View Article : Google Scholar : PubMed/NCBI
22	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
23	Tsukahara S, Nakajima D, Kuroda Y, Hojo R, Kageyama S and Fujimaki H: Effects of maternal toluene exposure on testosterone levels in fetal rats. Toxicol Lett. 185:79–84. 2009. View Article : Google Scholar : PubMed/NCBI
24	Liu F, Li XL, Lin T, He DW, Wei GH, Liu JH and Li LS: The cyclophosphamide metabolite, acrolein, induces cytoskeletal changes and oxidative stress in Sertoli cells. Mol Biol Rep. 39:493–500. 2012. View Article : Google Scholar : PubMed/NCBI
25	He X, Song W, Liu C, Chen S and Hua J: Rapamycin inhibits acrolein-induced apoptosis by alleviating ROS-driven mitochondrial dysfunction in male germ cells. Cell Prolif. 47:161–171. 2014. View Article : Google Scholar : PubMed/NCBI
26	Griswold SL and Behringer RR: Fetal Leydig cell origin and development. Sex Dev. 3:1–15. 2009. View Article : Google Scholar : PubMed/NCBI
27	O'Shaughnessy PJ, Baker PJ and Johnston H: The foetal Leydig cell-differentiation, function and regulation. Int J Androl. 29:90–108. 2006. View Article : Google Scholar : PubMed/NCBI
28	Habert R, Lejeune H and Saez JM: Origin, differentiation and regulation of fetal and adult Leydig cells. Mol Cell Endocrinol. 179:47–74. 2001. View Article : Google Scholar : PubMed/NCBI
29	Zhao B, Li L, Liu J, Li H, Zhang C1, Han P, Zhang Y, Yuan X, Ge RS and Chu Y: Exposure to perfluorooctane sulfonate in utero reduces testosterone production in rat fetal Leydig cells. PLoS One. 9:e788882014. View Article : Google Scholar : PubMed/NCBI
30	Lin H, Ge RS, Chen GR, Hu GX, Dong L, Lian QQ, Hardy DO, Sottas CM, Li XK and Hardy MP: Involvement of testicular growth factors in fetal Leydig cell aggregation after exposure to phthalate in utero. Proc Natl Acad Sci USA. 105:7218–7222. 2008. View Article : Google Scholar : PubMed/NCBI
31	Payne AH and Hales DB: Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones. Endocr Rev. 25:947–970. 2004. View Article : Google Scholar : PubMed/NCBI
32	Tyczewska M, Rucinski M, Ziolkowska A, Trejter M, Szyszka M and Malendowicz LK: Expression of selected genes involved in steroidogenesis in the course of enucleation-induced rat adrenal regeneration. Int J Mol Med. 33:613–623. 2014.PubMed/NCBI
33	Chadwick AC, Holme RL, Chen Y, Thomas MJ, Sorci-Thomas MG, Silverstein RL, Pritchard KA Jr and Sahoo D: Acrolein impairs the cholesterol transport functions of high density lipoproteins. PLoS One. 10:e01231382015. View Article : Google Scholar : PubMed/NCBI
34	Luu-The V: Assessment of steroidogenesis and steroidogenic enzyme functions. J Steroid Biochem Mol Biol. 137:176–182. 2013. View Article : Google Scholar : PubMed/NCBI
35	Ivell R and Bathgate RA: Reproductive biology of the relaxin-like factor (RLF/INSL3). Biol Reprod. 67:699–705. 2002. View Article : Google Scholar : PubMed/NCBI
36	Parent RA, Caravello HE and Hoberman AM: Reproductive study of acrolein on two generations of rats. Fundam Appl Toxicol. 19:228–237. 1992. View Article : Google Scholar : PubMed/NCBI
37	Kuwada M, Kawashima R, Nakamura K, Kojima H, Hasumi H, Maki J and Sugano S: Neonatal exposure to endocrine disruptors suppresses juvenile testis weight and steroidogenesis but spermatogenesis is considerably restored during puberty. Biochem Biophys Res Commun. 295:193–197. 2002. View Article : Google Scholar : PubMed/NCBI
38	Monroe RK and Halvorsen SW: Environmental toxicants inhibit neuronal Jak tyrosine kinase by mitochondrial disruption. Neurotoxicology. 30:589–598. 2009. View Article : Google Scholar : PubMed/NCBI
39	Shi Z, Feng Y, Wang J, Zhang H, Ding L and Dai J: Perfluorododecanoic acid-induced steroidogenic inhibition is associated with steroidogenic acute regulatory protein and reactive oxygen species in cAMP-stimulated Leydig cells. Toxicol Sci. 114:285–294. 2010. View Article : Google Scholar : PubMed/NCBI
40	Zhou L, Beattie MC, Lin CY, Liu J, Traore K, Papadopoulos V, Zirkin BR and Chen H: Oxidative stress and phthalate-induced down-regulation of steroidogenesis in MA-10 Leydig cells. Reprod Toxicol. 42:95–101. 2013. View Article : Google Scholar : PubMed/NCBI
41	Ayala A, Muñoz MF and Argüelles S: Lipid peroxidation: Production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev. 2014:3604382014. View Article : Google Scholar : PubMed/NCBI