Intrauterine exposure to bisphenol A promotes different effects in both neonatal and adult prostate of male and female gerbils (Meriones unguiculatus)

Substances that mimic endogenous hormones may alter the cell signaling that govern prostate development and predispose it to developing lesions in adult and senile life. Bisphenol A is able to mimic estrogens, and studies have demonstrated that low levels of exposure to this compound have caused alterations during prostate development. The aim of this study was to describe the prostate development in both male and female neonatal gerbils in normal conditions and under exposure to BPA during intrauterine life, and also to analyze whether the effects of intrauterine exposure to BPA remain in adulthood. Morphological, stereological, three‐dimensional reconstruction, and immunohistochemical methods were employed. The results demonstrated that in 1‐day‐old normal gerbils, the female paraurethral glands and the male ventral lobe are morphologically similar, although its tissue components—epithelial buds (EB), periurethral mesenchyme (PeM), paraurethral mesenchyme (PaM) or ventral mesenchymal pad (VMP), and smooth muscle (SM)—have presented different immunolabeling pattern for androgen receptor (AR), and for proliferating cell nuclear antigen (PCNA). Moreover, we observed a differential response of male and female prostate to intrauterine BPA exposure. In 1‐day‐old males, the intrauterine exposure to BPA caused a decrease of AR‐positive cells in the PeM and SM, and a decrease of the proliferative status in the EB. In contrast, no morphological alterations were observed in ventral prostate of adult males. In 1‐day‐old females, BPA exposure promoted an increase of estrogen receptor alpha (ERα) positive cells in PeM and PaM, a decrease of AR‐positive cells in EB and PeM, besides a reduction of cell proliferation in EB. Additionally, the adult female prostate of BPA‐exposed animals presented an increase of AR‐ and PCNA‐positive cells. These results suggest that the prostate of female gerbils were more susceptible to the intrauterine BPA effects, since they became more proliferative in adult life. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1740–1750, 2016.

[1]  S. Taboga,et al.  Prepubertal exposure to bisphenol‐A induces ERα upregulation and hyperplasia in adult gerbil female prostate , 2015, International journal of experimental pathology.

[2]  S. Taboga,et al.  Budding process during the organogenesis of the ventral prostatic lobe in mongolian gerbil , 2014, Microscopy research and technique.

[3]  N. Gharbi,et al.  Bisphenol A and human chronic diseases: current evidences, possible mechanisms, and future perspectives. , 2014, Environment international.

[4]  S. Taboga,et al.  Progesterone as a morphological regulatory factor of the male and female gerbil prostate , 2013, International journal of experimental pathology.

[5]  Ruili Huang,et al.  Bisphenol A affects androgen receptor function via multiple mechanisms. , 2013, Chemico-biological interactions.

[6]  J. M. Torres,et al.  Bisphenol A Exposure during Adulthood Alters Expression of Aromatase and 5α-Reductase Isozymes in Rat Prostate , 2013, PloS one.

[7]  S. Taboga,et al.  Prenatal testosterone exposure as a model for the study of endocrine-disrupting chemicals on the gerbil prostate , 2012, Experimental biology and medicine.

[8]  Sher Singh,et al.  Epigenetic Effects of Environmental Chemicals Bisphenol A and Phthalates , 2012, International journal of molecular sciences.

[9]  M. Wong,et al.  Bisphenol A (BPA) in China: a review of sources, environmental levels, and potential human health impacts. , 2012, Environment international.

[10]  R. Ge,et al.  Inhibitors of Testosterone Biosynthetic and Metabolic Activation Enzymes , 2011, Molecules.

[11]  P. Kelly,et al.  Misplaced Skene's Glands: Glandular Elements in the Lower Female Genital Tract That Are Variably Immunoreactive With Prostate Markers and That Encompass Vaginal Tubulosquamous Polyp and Cervical Ectopic Prostatic Tissue , 2011, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[12]  A. Haitel,et al.  The human female prostate-immunohistochemical study with prostate-specific antigen, prostate-specific alkaline phosphatase, and androgen receptor and 3-D remodeling. , 2011, The journal of sexual medicine.

[13]  G. Prins,et al.  Disruption of androgen receptor signaling in males by environmental chemicals , 2011, The Journal of Steroid Biochemistry and Molecular Biology.

[14]  C. Richter,et al.  Journal of Steroid Biochemistry and Molecular Biology Estrogenic Environmental Chemicals and Drugs: Mechanisms for Effects on the Developing Male Urogenital System , 2022 .

[15]  S. Taboga,et al.  Exposure to ethinylestradiol during prenatal development and postnatal supplementation with testosterone causes morphophysiological alterations in the prostate of male and female adult gerbils , 2011, International journal of experimental pathology.

[16]  S. Taboga,et al.  Tissue changes in senescent gerbil prostate after hormone deprivation leads to acquisition of androgen insensitivity , 2010, International journal of experimental pathology.

[17]  S. Taboga,et al.  Disorders related with ageing in the gerbil female prostate (Skene’s paraurethral glands) , 2010, International journal of experimental pathology.

[18]  G. Risbridger,et al.  Aromatase and regulating the estrogen:androgen ratio in the prostate gland , 2010, The Journal of Steroid Biochemistry and Molecular Biology.

[19]  P. Hunt,et al.  The Bisphenol A Experience: A Primer for the Analysis of Environmental Effects on Mammalian Reproduction1 , 2009, Biology of reproduction.

[20]  S. Taboga,et al.  Hormonal Oscillations During the Estrous Cycle Influence the Morphophysiology of the Gerbil (Meriones unguiculatus) Female Prostate (Skene Paraurethral Glands)1 , 2008, Biology of reproduction.

[21]  J. Toppari.  Environmental Endocrine Disrupters , 2008, Sexual Development.

[22]  Laura N. Vandenberg,et al.  Perinatal exposure to the xenoestrogen bisphenol-A induces mammary intraductal hyperplasias in adult CD-1 mice. , 2008, Reproductive toxicology.

[23]  S. Taboga,et al.  Antiestrogen Therapies Affect Tissue Homeostasis of the Gerbil (Meriones unguiculatus) Female Prostate and Ovaries1 , 2008, Biology of reproduction.

[24]  B. Timms.  Prostate development: a historical perspective. , 2008, Differentiation; research in biological diversity.

[25]  G. Risbridger,et al.  Estrogen-regulated development and differentiation of the prostate. , 2008, Differentiation; research in biological diversity.

[26]  G. Prins,et al.  Perinatal exposure to oestradiol and bisphenol A alters the prostate epigenome and increases susceptibility to carcinogenesis. , 2008, Basic & clinical pharmacology & toxicology.

[27]  W. Grin,et al.  The female prostate revisited: perineal ultrasound and biochemical studies of female ejaculate. , 2007, The journal of sexual medicine.

[28]  C. Richter,et al.  In vivo effects of bisphenol A in laboratory rodent studies. , 2007, Reproductive toxicology.

[29]  G. Prins,et al.  Developmental estrogen exposures predispose to prostate carcinogenesis with aging. , 2007, Reproductive toxicology.

[30]  Frederick S vom Saal,et al.  Estrogenic chemicals in plastic and oral contraceptives disrupt development of the fetal mouse prostate and urethra. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[31]  J C Fiala,et al.  Reconstruct: a free editor for serial section microscopy , 2005, Journal of microscopy.

[32]  S. Madersbacher,et al.  Benign prostatic hyperplasia: age-related tissue-remodeling , 2005, Experimental Gerontology.

[33]  H. F. Carvalho,et al.  Structure, histochemistry, and ultrastructure of the epithelium and stroma in the gerbil (Meriones unguiculatus) female prostate. , 2003, Tissue & cell.

[34]  S. Chattopadhyay,et al.  Antiandrogenic effects of bisphenol A and nonylphenol on the function of androgen receptor. , 2003, Toxicological sciences : an official journal of the Society of Toxicology.

[35]  Rajvir Dahiya,et al.  Hormonal, cellular, and molecular control of prostatic development. , 2003, Developmental biology.

[36]  E. Portiansky,et al.  Morphological characterization of the female prostate (Skene's gland or paraurethral gland) of Lagostomus maximus maximus. , 2002, Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft.

[37]  O. Grace,et al.  The role of smooth muscle in regulating prostatic induction. , 2002, Development.

[38]  H. Satoh,et al.  Morphological and Immunohistochemical Characteristics of the Heterogeneous Prostate-Like Glands (Paraurethral Gland) Seen in Female Brown-Norway Rats , 2001, Toxicologic pathology.

[39]  A. Thomson.  Role of androgens and fibroblast growth factors in prostatic development. , 2001, Reproduction.

[40]  S. Oishi,et al.  Disposition of orally administered 2,2-Bis(4-hydroxyphenyl)propane (Bisphenol A) in pregnant rats and the placental transfer to fetuses. , 2000, Environmental health perspectives.

[41]  R. Cattley,et al.  Pubertal development and reproductive functions of Crl:CD BR Sprague-Dawley rats exposed to bisphenol A during prenatal and postnatal development. , 2000, Toxicological sciences : an official journal of the Society of Toxicology.

[42]  G. Cunha,et al.  Stromal-epithelial interactions and heterogeneity of proliferative activity within the prostate. , 1986, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[43]  H. Helminen,et al.  A histoquantitative study on the effects of castration on the rat ventral prostate lobe. , 1981, Journal of anatomy.

[44]  R. Shehata.  Female prostate and urethral glands in the home rat, Rattus norvegicus. , 1980, Acta anatomica.

[45]  E. Weibel,et al.  Principles and methods for the morphometric study of the lung and other organs. , 1963, Laboratory investigation; a journal of technical methods and pathology.

[46]  E. Witschi,et al.  Genetics of the Female Prostate in Rats. , 1947, Genetics.

[47]  S. Taboga,et al.  Prenatal exposure to testosterone masculinises the female gerbil and promotes the development of lesions in the prostate (Skene's gland). , 2015, Reproduction, fertility, and development.

[48]  Kurunthachalam Kannan,et al.  Serum bisphenol A pharmacokinetics and prostate neoplastic responses following oral and subcutaneous exposures in neonatal Sprague-Dawley rats. , 2011, Reproductive toxicology.

[49]  荒瀬 栄樹.  Endocrine disrupter bisphenol A increases in situ estrogen production in the mouse urogenital sinus , 2011 .

[50]  V. Jakubovská,et al.  Ultrastructure of the normal adult human female prostate gland (Skene’s gland) , 2000, Anatomy and Embryology.