Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2019

Open Access 01-12-2019 | Estradiol | Research

Comparative study of environmental pollutants bisphenol A and bisphenol S on sexual differentiation of anteroventral periventricular nucleus and spermatogenesis

Authors: Naham John, Humaira Rehman, Suhail Razak, Mehwish David, Waheed Ullah, Tayyaba Afsar, Ali Almajwal, Iftikhar Alam, Sarwat Jahan

Published in: Reproductive Biology and Endocrinology | Issue 1/2019

Login to get access

Abstract

Background

Bisphenol A is well known endocrine-disrupting chemical while Bisphenol S was considered a safe alternative. The present study aims to examine the comparative effects of xenobiotic bisphenol-A (BPA) and its substitute bisphenol-S (BPS) on spermatogenesis and development of sexually dimorphic nucleus population of dopaminergic neurons in the anteroventral periventricular nucleus (AVPV) of the hypothalamus in male pups.

Methods

Sprague Dawley rat’s pups were administered subcutaneously at the neonatal stage from postnatal day PND1 to PND 27. Thirty animals were divided into six experimental groups (6 animals/group). The first group served as control and was provided with normal olive oil. The four groups were treated with 2 μg/kg and 200 μg/kg of BPA and BPS, respectively. The sixth group was given with 50 μg/kg of estradiol dissolved in olive oil as a standard to find the development of dopaminergic tyrosine hydroxylase neurons in AVPV regions. Histological analysis for testicular tissues and immunohistochemistry for brain tissues was performed.

Results

The results revealed adverse histopathological changes in testis after administration of different doses of BPA and BPS. These degenerative changes were marked by highly significant (p < 0.001) decrease in tubular and luminal diameters of seminiferous tubule and epithelial height among bisphenols treated groups as compared to control. Furthermore, significantly increased (p < 0.001) TH-ir cell bodies in the AVPV region of the brain with 200 μg/kg dose of BPA and BPS was evident.

Conclusion

It is concluded that exposure of BPA and BPS during a critical developmental period can structural impairments in testes and affects sexual differentiation of a dimorphic dopaminergic population of AVPV region of hypothalamus in the male brain.
Literature
1.
Anway MD, Skinner MK. Epigenetic transgenerational actions of endocrine disruptors. Endocrinology. 2006;147:s43–9.CrossRef
2.
Arnich N, Canivenc-Lavier M-C, Kolf-Clauw M, Coffigny H, Cravedi J-P, Grob K, Macherey A-C, Masset D, Maximilien R, Narbonne J-F. Conclusions of the French food safety agency on the toxicity of bisphenol A. Int J Hyg Environ Health. 2011;214:271–5.CrossRef
3.
Braun JM, Kalkbrenner AE, Calafat AM, Bernert JT, Ye X, Silva MJ, Barr DB, Sathyanarayana S, Lanphear BP. Variability and predictors of urinary bisphenol a concentrations during pregnancy. Environ Health Perspect. 2011;119:131–40.CrossRef
4.
Bu L, Lephart ED. AVPV neurons containing estrogen receptor-beta in adult male rats are influenced by soy isoflavones. BMC Neurosci. 2007;8:13–20.
5.
Calafat AM, Ye X, Wong L-Y, Reidy JA, Needham LL. Exposure of the US population to bisphenol a and 4-tertiary-octylphenol: 2003–2004. Environ Health Perspect. 2008;116:139.CrossRef
6.
Caserta D, Mantovani A, Marci R, Fazi A, Ciardo F, La Rocca C, Maranghi F, Moscarini M. Environment and women’s reproductive health. Hum Reprod Update. 2011;17:418–33.CrossRef
7.
Catanese MC, Vandenberg LN. Bisphenol S (BPS) alters maternal behavior and brain in mice exposed during pregnancy/lactation and their daughters. Endocrinology. 2016;158:516–30.
8.
Chen Y, Shu L, Qiu Z, Lee DY, Settle SJ, Hee SQ, Telesca D, Yang X, Allard P. Exposure to the BPA-substitute bisphenol S causes unique alterations of germline function. PLoS Genet. 2016;12:e1006223–32.CrossRef
9.
Colledge WH. Kisspeptins and GnRH neuronal signalling. Trends Endocrinol Metab. 2009;20:115–21.CrossRef
10.
Coulier L, Bradley EL, Bas RC, Verhoeckx KCM, Driffield M, Harmer N, Castle L. Analysis of reaction products of food contaminants and ingredients: bisphenol a diglycidyl ether (BADGE) in canned foods. J Agric Food Chem. 2010;58:4873–82.CrossRef
11.
Eladak S, Grisin T, Moison D, Guerquin M-J, N’Tumba-Byn T, Pozzi-Gaudin S, Benachi A, Livera G, Rouiller-Fabre V, Habert R. A new chapter in the bisphenol a story: bisphenol S and bisphenol F are not safe alternatives to this compound. Fertil Steril. 2015;103:11–21.CrossRef
12.
Forger NG, Rosen GJ, Waters EM, Jacob D, Simerly RB, De Vries GJ. Deletion of Bax eliminates sex differences in the mouse forebrain. Proc Natl Acad Sci U S A. 2004;101:13666–71.CrossRef
13.
Gámez JM, Penalba R, Cardoso N, Ponzo O, Carbone S, Pandolfi M, Scacchi P, Reynoso R. Low dose of bisphenol a impairs the reproductive axis of prepuberal male rats. J Physiol Biochem. 2014;70:239–46.CrossRef
14.
Gore AC. Neuroendocrine systems as targets for environmental endocrine-disrupting chemicals. Fertil Steril. 2008;89:e101.CrossRef
15.
Gregoraszczuk EL, Ptak A. Endocrine-disrupting chemicals: some actions of POPs on female reproduction. Int J Endocrinol. 2013;2013–20.
16.
Henley DV, Korach KS. Endocrine-disrupting chemicals use distinct mechanisms of action to modulate endocrine system function. Endocrinology. 2006;147:s25–32.CrossRef
17.
Hong J, Chen F, Wang X, Bai Y, Zhou R, Li Y, Chen L. Exposure of preimplantation embryos to low-dose bisphenol A impairs testes development and suppresses histone acetylation of StAR promoter to reduce production of testosterone in mice. Mol Cell Endocrinol. 2016;427:101–11.CrossRef
18.
Jacob DA, Temple JL, Patisaul HB, Young LJ, Rissman EF. Coumestrol antagonizes neuroendocrine actions of estrogen via the estrogen receptor α. Exp Biol Med. 2001;226:301–6.CrossRef
19.
Jahnukainen K, Chrysis D, Hou M, Parvinen M, Eksborg S, Söder O. Increased apoptosis occurring during the first wave of spermatogenesis is stage-specific and primarily affects midpachytene spermatocytes in the rat testis. Biol Reprod. 2004;70:290–6.CrossRef
20.
Ji K, Hong S, Kho Y, Choi K. Effects of bisphenol S exposure on endocrine functions and reproduction of zebrafish. Environ Sci Technol. 2013;47:8793–800.CrossRef
21.
Jin P, Wang X, Chang F, Bai Y, Li Y, Zhou R, Chen L. Low dose bisphenol a impairs spermatogenesis by suppressing reproductive hormone production and promoting germ cell apoptosis in adult rats. J Biomed Res. 2013;27:135.PubMed
22.
Kavlock RJ, Daston GP, DeRosa C, Fenner-Crisp P, Gray LE, Kaattari S, Lucier G, Luster M, Mac MJ, Maczka C. Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the US EPA-sponsored workshop. Environ Health Perspect. 1996;104:715.PubMedPubMedCentral
23.
Kazim SF, del Carmen Cardenas-Aguayo M, Arif M, Blanchard J, Fayyaz F, Grundke-Iqbal I, Iqbal K. Sera from children with autism induce autistic features which can be rescued with a CNTF small peptide mimetic in rats. PLoS One. 2015;10:e0118627.CrossRef
24.
Kinch CD, Ibhazehiebo K, Jeong J-H, Habibi HR, Kurrasch DM. Low-dose exposure to bisphenol A and replacement bisphenol S induces precocious hypothalamic neurogenesis in embryonic zebrafish. Proc Natl Acad Sci. 2015;112:1475–80.CrossRef
25.
Kuruto-Niwa R, Nozawa R, Miyakoshi T, Shiozawa T, Terao Y. Estrogenic activity of alkylphenols, bisphenol S, and their chlorinated derivatives using a GFP expression system. Environ Toxicol Pharmacol. 2005;19:121–30.CrossRef
26.
Liao C, Kannan K. Concentrations and profiles of bisphenol A and other bisphenol analogues in foodstuffs from the United States and their implications for human exposure. J Agric Food Chem. 2013;61:4655–62.CrossRef
27.
Liao C, Liu F, Alomirah H, Loi VD, Mohd MA, Moon H-B, Nakata H, Kannan K. Bisphenol S in urine from the United States and seven Asian countries: occurrence and human exposures. Environ Sci Technol. 2012;46:6860–6.CrossRef
28.
Liu C, Duan W, Zhang L, Xu S, Li R, Chen C, He M, Lu Y, Wu H, Yu Z. Bisphenol A exposure at an environmentally relevant dose induces meiotic abnormalities in adult male rats. Cell Tissue Res. 2014;355:223–32.CrossRef
29.
Ma S, Shi W, Wang X, Song P, Zhong X. Bisphenol a exposure during pregnancy alters the mortality and levels of reproductive hormones and genes in offspring mice. Biomed Res Int. 2017;2017.
30.
McCaffrey KA, Jones B, Mabrey N, Weiss B, Swan SH, Patisaul HB. Sex specific impact of perinatal bisphenol A (BPA) exposure over a range of orally administered doses on rat hypothalamic sexual differentiation. Neurotoxicology. 2013;36:55–62.CrossRef
31.
Molina-Molina J-M, Amaya E, Grimaldi M, Sáenz J-M, Real M, Fernández MF, Balaguer P, Olea N. In vitro study on the agonistic and antagonistic activities of bisphenol-S and other bisphenol-A congeners and derivatives via nuclear receptors. Toxicol Appl Pharmacol. 2013;272:127–36.CrossRef
32.
Naciff JM, Hess KA, Overmann GJ, Torontali SM, Carr GJ, Tiesman JP, Foertsch LM, Richardson BD, Martinez JE, Daston GP. Gene expression changes induced in the testis by transplacental exposure to high and low doses of 17α-ethynyl estradiol, genistein, or bisphenol A. Toxicol Sci. 2005;86:396–416.CrossRef
33.
Naderi M, Wong MYL, Gholami F. Developmental exposure of zebrafish (Danio rerio) to bisphenol-S impairs subsequent reproduction potential and hormonal balance in adults. Aquat Toxicol. 2014;148:195–203.CrossRef
34.
Ogonuki N, Inoue K, Hirose M, Miura I, Mochida K, Sato T, Mise N, Mekada K, Yoshiki A, Abe K. A high-speed congenic strategy using first-wave male germ cells. PLoS One. 2009;4:e4943.CrossRef
35.
Orikasa C, Sakuma Y. Possible involvement of preoptic estrogen receptor β positive cells in luteinizing hormone surge in the rat. Domest Anim Endocrinol. 2003;25:83–92.CrossRef
36.
Patisaul HB, Fortino AE, Polston EK. Neonatal genistein or bisphenol-A exposure alters sexual differentiation of the AVPV. Neurotoxicol Teratol. 2006;28:111–8.CrossRef
37.
Phrakonkham P, Viengchareun S, Belloir C, Lombès M, Artur Y, Canivenc-Lavier M-C. Dietary xenoestrogens differentially impair 3T3-L1 preadipocyte differentiation and persistently affect leptin synthesis. J Steroid Biochem Mol Biol. 2008;110:95–103.CrossRef
38.
Rajasärkkä J, Koponen J, Airaksinen R, Kiviranta H, Virta M. Monitoring bisphenol A and estrogenic chemicals in thermal paper with yeast-based bioreporter assay. Anal Bioanal Chem. 2014;406:5695–702.CrossRef
39.
Ramsay DJ, Booth D. Thirst: physiological and psychological aspects: Springer Science & Business Media; 2012.
40.
Richter CA, Birnbaum LS, Farabollini F, Newbold RR, Rubin BS, Talsness CE, Vandenbergh JG, Walser-Kuntz DR, vom Saal FS. In vivo effects of bisphenol A in laboratory rodent studies. Reprod Toxicol. 2007;24:199–224.CrossRef
41.
Rubin BS. Bisphenol A: an endocrine disruptor with widespread exposure and multiple effects. J Steroid Biochem Mol Biol. 2011;127:27–34.CrossRef
42.
Rubin BS, Lenkowski JR, Schaeberle CM, Vandenberg LN, Ronsheim PM, Soto AM. Evidence of altered brain sexual differentiation in mice exposed perinatally to low, environmentally relevant levels of bisphenol A. Endocrinology. 2006;147:3681–91.CrossRef
43.
Rubin BS, Murray MK, Damassa DA, King JC, Soto AM. Perinatal exposure to low doses of bisphenol A affects body weight, patterns of estrous cyclicity, and plasma LH levels. Environ Health Perspect. 2001;109:675.CrossRef
44.
Sakaue M, Ohsako S, Ishimura R, Kurosawa S, Kurohmaru M, Hayashi Y, Aoki Y, Yonemoto J, Tohyama C. Bisphenol-A affects spermatogenesis in the adult rat even at a low dose. J Occup Health. 2001;43:185–90.CrossRef
45.
Salian S, Doshi T, Vanage G. Neonatal exposure of male rats to bisphenol A impairs fertility and expression of sertoli cell junctional proteins in the testis. Toxicology. 2009;265:56–67.CrossRef
46.
Schlesser HN. Effect of endocrine disruptors on the male mouse reproductive system: University of Illinois at Urbana-Champaign; 2009.
47.
Semaan SJ, Kauffman AS. Sexual differentiation and development of forebrain reproductive circuits. Curr Opin Neurobiol. 2010;20:424–31.CrossRef
48.
Simerly RB, Swanson LW, Gorski RA. The distribution of monoaminergic cells and fibers in a periventricular preoptic nucleus involved in the control of gonadotropin release: immunohistochemical evidence for a dopaminergic sexual dimorphism. Brain Res. 1985;330:55–64.CrossRef
49.
Simerly RB, Zee MC, Pendleton JW, Lubahn DB, Korach KS. Estrogen receptor-dependent sexual differentiation of dopaminergic neurons in the preoptic region of the mouse. Proc Natl Acad Sci. 1997;94:14077–82.CrossRef
50.
Song S, Zhang L, Zhang H, Wei W, Jia L. Perinatal BPA exposure induces hyperglycemia, oxidative stress and decreased adiponectin production in later life of male rat offspring. Int J Environ Res Public Health. 2014;11:3728–42.CrossRef
51.
Soto AM, Brisken C, Schaeberle C, Sonnenschein C. Does cancer start in the womb? Altered mammary gland development and predisposition to breast cancer due to in utero exposure to endocrine disruptors. J Mammary Gland Biol Neoplasia. 2013;18:199–208.CrossRef
52.
Takemura H, Ma J, Sayama K, Terao Y, Zhu BT, Shimoi K. In vitro and in vivo estrogenic activity of chlorinated derivatives of bisphenol A. Toxicology. 2005;207:215–21.CrossRef
53.
Uenoyama Y, Pheng V, Tsukamura H, Maeda K. The roles of kisspeptin revisited: inside and outside the hypothalamus. J Reprod Dev. 2016;62:537–45.CrossRef
54.
Ullah H, Jahan S, Ain QU, Shaheen G, Ahsan N. Effect of bisphenol S exposure on male reproductive system of rats: a histological and biochemical study. Chemosphere. 2016;152:383–91.CrossRef
55.
Wolstenholme JT, Rissman EF, Connelly JJ. The role of bisphenol A in shaping the brain, epigenome and behavior. Horm Behav. 2011;59:296–305.CrossRef
56.
Ye X, Wong L-Y, Kramer J, Zhou X, Jia T, Calafat AM. Urinary concentrations of bisphenol A and three other bisphenols in convenience samples of US adults during 2000–2014. Environ Sci Technol. 2015;49:11834–39.CrossRef
57.
Zup SL, Carrier H, Waters EM, Tabor A, Bengston L, Rosen GJ, Simerly RB, Forger NG. Overexpression of bcl-2 reduces sex differences in neuron number in the brain and spinal cord. J Neurosci. 2003;23:2357–62.CrossRef
Metadata
Title
Comparative study of environmental pollutants bisphenol A and bisphenol S on sexual differentiation of anteroventral periventricular nucleus and spermatogenesis
Authors
Naham John
Humaira Rehman
Suhail Razak
Mehwish David
Waheed Ullah
Tayyaba Afsar
Ali Almajwal
Iftikhar Alam
Sarwat Jahan
Publication date
01-12-2019
Publisher
BioMed Central
Keyword
Estradiol
Published in
Reproductive Biology and Endocrinology / Issue 1/2019
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-019-0491-x

Other articles of this Issue 1/2019

Reproductive Biology and Endocrinology 1/2019 Go to the issue

Research

Letrozole supplementation during controlled ovarian stimulation in expected high responders: a pilot randomized controlled study

Research

Proteomic alterations underlie an association with teratozoospermia in obese mice sperm

Research

Possible involvement of the RARRES2/CMKLR1-system in metabolic and reproductive parameters in Holstein dairy cows

Research

MicroRNA-451 is downregulated in the follicular fluid of women with endometriosis and influences mouse and human embryonic potential

Research

The risk of secondary sex ratio imbalance and increased monozygotic twinning after blastocyst transfer: data from the Japan Environment and Children’s Study

Research

The impact of follicle-flushing during oocyte collection on embryo development of in-vitro fertilization