The aim of the present study was to assess and compare the individual adverse effects of bisphenol A (BPA) and octylphenol (OP) on the reproductive system of prepubertal male rats. Rats were exposed to BPA and OP at doses of 125 and 250 mg/kg/day, by gavage, for 90 days. At the end of the study, the testes, epididymis, prostate gland, and seminal vesicle were removed and examined histopathologically. Also, 3-β-hydroxysteroid dehydrogenase expressions were analyzed and serum testosterone and luteinizing hormone (LH) levels were measured. Sperm head count of caput epididymis was performed using a hemocytometer. Seminiferous and epididymal round tubules were evaluated for tubule diameter, lumen diameter, and height of tubule epithelium. There were significant increases in relative testes weights in BPA125, OP125, and OP250 groups compared with the control. Atrophic tubules, pyknotic tubules, combined tubules, congestion, vacuolization of Sertoli cell, cell debris in the lumen, tubules without sperm, and degeneration of tubules were noted in the tissue specimens obtained from the treatment groups compared with the control group. Sperm head counts were decreased in all treatment groups except for the low-dose BPA group. Testosterone (T) levels decreased in the BPA and high-dose OP treatment groups. LH levels increased in BPA treatment groups and the low-dose OP treatment group and decreased in the high-dose OP group. Epithelial height of high-dose BPA and OP treatment groups increased compared with the control group. Furthermore tubular height of low-dose BPA and high-dose OP groups increased with respect to control levels. In the OP250 treatment group, thyroxine hormone level was increased compared to other groups. Also, in the OP125 treatment group, triiodothyronine hormone level was increased compared with other groups.
The results of this study showed that BPA and OP affect the steroidogenic enzyme expression and T production in Leydig cells. In conclusion, BPA and OP have adverse effects on the male reproductive system of prepubertal rats.
AdemolloNFerraraFDeliseM. (2008) Nonylphenol and octylphenol in human breast milk. Environment International34: 984–87.
2.
AhelMGigerW (1993) Aqueous solubility of alkyl-phenols and alkylphenol polyethoxylates. Chemosphere8: 1461–1470.
3.
AkingbemiBTSottasCMKoulovaAI. (2004) Inhibition of testicular steroidogenesis by the xenoestrogen bisphenol A is associated with reduced pituitary luteinizing hormone secretion and decreased steroidogenic enzyme gene expression in rat Leydig cells. Endocrinology145: 592–603.
4.
AydoğanMBarlasN (2006) Effects of maternal 4-tert-octylphenol exposure on the reproductive tract of male rats at adulthood. Reproductive Toxicology22: 455–460.
5.
BaiYChangFZhouR. (2011) Increase of anteroventral periventricular kisspeptin neurons and generation of E2-induced LH-surge system in male rats exposed perinatally to environmental dose of bisphenol-A. Endocrinology152: 1562–1571.
6.
BarlasNAydoğanM (2009) Histopathologic effects of maternal 4-tert-octylphenol exposure on liver, kidney and spleen of rats at adulthood. Archives of Toxicology83: 341–349.
7.
BianQQianJXuL. (2006) The toxic effect of 4-tert-octylphenol on the reproductive system of male rat. Food and Chemical Toxicology44: 1355–1361.
8.
BoockforFRBlakeCA (1997) Chronic administration of 4-tert-octylphenol to adult male rats causes shrinkage of the testes and male accessory sex organs, disrupts spermatogenesis, and increases the incidence of sperm deformities. Biology of Reproduction57: 267–277.
9.
CardosoNPandolfiMLavalleJ. (2011) Probable gamma-aminobutyric acid involvement in bisphenol A effect at the hypothalamic level in adult male rats. Journal of Physiology and Biochemistry67: 559–567.
10.
CéspedesRLacorteSGinebredaA. (2008) Occurrence and fate of alkylphenols and alkylphenol ethoxylates in sewage treatment plants and impact on receiving waters along the Ter River (Catalonia, NE Spain). Environmental Pollution153: 384–392.
11.
D’CruzSCJubendradassRJayakanthanM. (2012) Bisphenol A impairs insulin signaling and glucose homeostasis and decreases steroidogenesis in rat testis: an in vivo and in silico study. Food and Chemical Toxicology50: 1124–1133.
12.
DekantWColnotT (2013) Endocrine effects of chemicals: aspects of hazard identification and human health risk assessment. Toxicology Letters223: 280–286.
13.
European Council for Alkylphenols and Derivatives and the Alkylphenols and Ethoxylates Research Council (2012) Comments on the REACH Annex XV Report: Proposal for identification of a substance as a CMR Cat. 1A or 1B, PBT or vPvB, or a substance of an equivalent level of concern: 4-nonylphenol, branched and linear, 17 October 2012.
14.
GámezJMPenalbaRCardosoN. (2015) Exposure to a low dose of bisphenol A impairs pituitary-ovarian axis in prepubertal rats: effects on early folliculogenesis. Environmental Toxicology and Pharmacology39: 9–15.
15.
GoreAC (2001) Environmental toxicant effects on neuroendocrine function. Endocrinology14: 235–246.
16.
HerathCBWanzhuJWatanabeG. (2004) Adverse effects of environmental toxicants, octylphenol and bisphenol A, on male reproductive functions in pubertal rats. Endocrinology25: 163–172.
17.
HowdeshellKLHotchkissAKThayerKA. (1999) Exposure to bisphenol A advances puberty. Nature401: 763–764.
18.
ImaidaKShiraiT (2000) Endocrine-disrupting chemicals and carcinogenesis-breast, testis and prostate cancer. Nippon Rinsho58: 2527–2532.
19.
JagerCBornmanMSOosthuizenJM (1999) The effect of p-nonylphenol on the fertility potential of male rats after gestational, lactational and direct exposure. Andrologia31: 107–113.
20.
KanekoMOkadaRYamamotoK. (2008) Bisphenol A acts differently from and independently of thyroid hormone in suppressing thyrotropin release from the bullfrog pituitary. General and Comparative Endocrinology155: 574–580.
21.
KimSKLeeHJYangH. (2004) Prepubertal exposure to 4-tert-octylphenol induces apoptosis of testicular germ cells in adult rat. Archives of Andrology50: 427–441.
22.
KimHHKwakDHYonJM. (2007) Differential expression of 3beta-hydroxysteroid dehydrogenase mRNA in rat testes exposed to endocrine disruptors. Journal of Reproductive Development53: 465–471.
23.
KnaakJBSullivanLJ (1966) Metabolism of bisphenol A in the rat. Toxicology and Applied Pharmacology8: 175–184.
24.
KrishnanAVStathisPPermuthSF. (1993) Bisphenol-A: an estrogenic substance is released from polycarbonate flasks during autoclaving. Endocrinology132: 2279–2286.
25.
KumaranSKavithaCRameshM. (2011) Toxicity studies of nonylphenol and octylphenol: hormonal, hematological and biochemical effects in Clarias gariepinus. Journal of Applied Toxicology31: 752–776.
26.
LiuJWangRHuangB. (2011) Distribution and bioaccumulation of steroidal and phenolic endocrine disrupting chemicals in wild fish species from Dianchi Lake, China. Environmental Pollution159: 2815–2822.
27.
LukeMCoffeyD (1994) The male sex accessory tissues. In: KnobilENeillJ (eds) The Physiology of Reproduction. 2nd ed. New York: Raven Press, pp. 1435–1487.
28.
ManfoFPJubendradassRNantiaEA. (2014) Adverse effects of bisphenol A on male reproductive function. Reviews of Environmental Contamination and Toxicology228: 57–82.
29.
MatherJPSaezJMHaourF (1981) Primary cultures of Leydig cells from rat, mouse and pig: advantages of porcine cells from the study of gonadotropin regulation of Leydig cell function. Steroids38: 35–44.
30.
MayerTBennieDRosaF. (2007) Occurrence of alkylphenolic substances in a Great Lakes coastal marsh, Cootes Paradise, ON, Canada. Environmental Pollution3: 683–690.
31.
NagaoTYoshimuraSSaitoY. (2001) Reproductive effects in male and female rats from neonatal exposure to p-octylphenol. Reproductive Toxicology15: 683–692.
32.
NagelSCVom SaalFSThayerKA. (1997) Relative binding affinity-serum modified access (RBA-SMA) assay predicts the relative in vivo bioactivity of the xenoestrogens bisphenol A and octylphenol. Environmental Health Perspective105: 70–76.
33.
NakamuraDYanagibaYDuanZ. (2010) Bisphenol A may cause testosterone reduction by adversely affecting both testis and pituitary systems similar to estradiol. Toxicology Letters194: 16–25.
34.
NanjappaMKSimonLAkingbemiBT (2012) The industrial chemical bisphenol A (BPA) interferes with proliferative activity and development of steroidogenic capacity in rat Leydig cells. Biology of Reproduction86: 1–12.
35.
PreslockJP (1980) A review of in vitro testicular steroidogenesis in rodents, monkeys and humans. Journal of Steroid Biochemistry8: 965–975.
36.
SadowskiRNParkPNeeseSL. (2014) Effects of perinatal bisphenol A exposure during early development on radial arm maze behavior in adult male and female rats. Neurotoxicology and Teratology42: 17–24.
37.
SvechnikovKVSultanaTSoderO (2001) Age-dependent stimulation of Leydig cell steroidogenesis by interleukin-1 isoforms. Molecular and Cell Endocrinology2: 193–201.
38.
TakahashiOOishiS (2001) Testicular toxicity of dietary 2,2-bis (4-hydroxyphenyl) propane (bisphenol A) in F344 rats. Archives of Toxicology75: 42–45.
39.
ToheiASudaSTayaK. (2001) Bisphenol A inhibits testicular functions and increases luteinizing hormone secretion in adult male rats. Experimental Biology and Medicine226: 216–221.
40.
U.S. Department of Health and Human Services (1982) NTP Technical Report on the Carcinogenesis Bioassay of Bisphenol A (CAS no. 80-05-7) in F344 Rats and B6C3F1 Mice (Feed Study). National Toxicology Program-80-35, NIH Publication No. 82–1771. Bethesda, MD: U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health.
41.
U.S. Environmental Protection Agency (2010) Bisphenol A Action Plan, (CASRN 80-05-7) [CA Index Name: Phenol, 4,4’-(1-methylethylidene)bis- ], pp. 1–22, 15 April 2010.
42.
UpmeierADegenGHDielP. (2000) Toxicokinetics of bisphenol A in female DA/Han rats after a single i.v. and oral administration. Archives of Toxicology74: 431–436.
43.
Vom SaalFSCookePSBuchananDL. (1998) A physiologically based approach to the study of bisphenol A and other estrogenic chemicals on the size of reproductive organs, daily sperm production and behavior. Toxicology and Industrial Health14: 239–260.
44.
WatanabeHSuzukiAKobayashiM. (2003) Analysis of temporal changes in the expression of estrogen-regulated genes in the uterus. Journal of Molecular Endocrinology30: 347–358.
45.
WhiteRJoblingSHoareSA. (1994) Environmentally persistent alkylphenolic compounds are estrogenic. Endocrinology135: 175–182.
46.
YıldızNBarlasN (2013) Hepatic and renal functions in growing male rats after bisphenol A and octylphenol exposure. Human and Experimental Toxicology32: 675–686.
47.
YoshidaMKatsudaSTakenakaA. (2001) Effects of neonatal exposure to a high-dose p-tert-octylphenol on the male reproductive tract in rats. Toxicology Letters121: 21–33.
48.
ZhaoJLYingGGWangL. (2009) Determination of phenolic endocrine disrupting chemicals and acidic pharmaceuticals in surface water of the pearl rivers in south china by gas chromatography-negative chemical ionization-mass spectrometry. Science of the Total Environment407: 962–974.
