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Early prostate development and its association with late-life prostate disease

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Abstract

The development of the prostate is an emerging priority area for prostate biologists. Early changes in prostate development permanently alter prostate morphology and function and an understanding of the permanent nature of early events that may influence the onset of late-life disease is vital. Two of the inherent problems involve associating exposure in early life with outcome in late life or maturity and accounting for the influence of genetic, environmental, dietary or metabolic factors during the intervening period. Any one of these factors, alone or in combination, might lead to an explanation of the discrepancies found in the literature regarding the influence of early changes to the prostate in later life. Therefore, it is important to establish a causal link between the hormonal changes that occur during the fetal/neonatal period and that imprint the gland and the onset of late-life pathology. In order to achieve this goal, several technical challenges need to be overcome to permit the objective assessment of prostate branching morphogenesis. Stereological techniques now allow the quantification of several parameters of branching morphogenesis and the identification of specific early changes that are permanent and irreversible with a late-life outcome. This methodology provides the means to determine the action of a range of genes or hormone/growth factors that have been implicated in prostate development and disease.

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References

  • Abbott BD, Lin TM, Rasmussen NT, Albrecht RM, Schmid JGE, Peterson RE (2003) Lack of expression of EGF and TGF-alpha in the fetal mouse alters formation of prostatic epithelial buds and influences the response to TCDD. Toxicol Sci 76:427–436

    Article  PubMed  Google Scholar 

  • Almahbobi G, Hedwards S, Fricout G, Jeulin D, Bertram JF, Risbridger GP (2005) Computer-based detection of neonatal changes to branching morphogenesis reveals different mechanisms of and predicts prostate enlargement in mice haplo-insufficient for bone morphogenetic protein 4. J Pathology 206:52–61

    Article  Google Scholar 

  • Arai Y (1970) Nature of metaplasia in rat coagulating glands induced by neonatal treatment with estrogen. Endocrinology 86:918–920

    PubMed  Google Scholar 

  • Arai Y, Mori T, Suzuki Y, Bern HA (1983) Long-term effects of perinatal exposure to sex steroids and diethylstilbestrol on the reproductive system of male mammals. In: Bourne GH, Danielle JF (eds) International review of cytology, vol. 84. Academic Press, New York, pp 235–268

    Google Scholar 

  • Ashby J, Tinwell H, Haseman J (1999) Lack of effects for low dose levels of bisphenol A and diethylstilbestrol on the prostate gland of CF1 mice exposed in utero. Regul Toxicol Pharmacol 30:156–166

    Article  PubMed  Google Scholar 

  • Ball WD (1974) Development of the rat salivary glands. 3. Mesenchymal specificity in the morphogenesis of the embryonic submaxillary and sublingual glands of the rat. J Exp Zool 188:277–288

    Article  PubMed  Google Scholar 

  • Bibbo M, Gill WB, Azizi F, Blough R, Fang VS, Rosenfield RL, Schumacher GF, Sleeper K, Sonek MG, Wied GL (1977) Follow-up study of male and female offspring of DES-exposed mothers. Obstet Gynecol 49:1–8

    PubMed  Google Scholar 

  • Bigsby R, Chapin RE, Daston GP, Davis BJ, Gorski J, Gray LE, Howdeshell KL, Zoeller RT, Saal FS vom (1999) Evaluating the effects of endocrine disruptors on endocrine function during development. Environ Health Perspect 107 (Suppl 4):613–618

    Google Scholar 

  • Chahoud I (2003) Correspondence: adverse health effects of bisphenol A: Chahoud’s response. Environ Health Perspect 111:A383

    Google Scholar 

  • Chang WY, Birch L, Woodham C, Gold LI, Prins GS (1999) Neonatal estrogen exposure alters the transforming growth factor-b signaling system in the developing rat prostate and blocks the transient p21cip/waf1 expression associated with epithelial differentiation. Endocrinology 140:2801–2813

    Article  PubMed  Google Scholar 

  • Crelin ES (1975) Development of the lower respiratory system. Ciba Clinical Symposia 27:3–28

    Google Scholar 

  • Cullen-McEwen LA, Fricout G, Harper IS, Jeulin D, Bertram JF (2002) Quantitation of 3D ureteric branching morphogenesis in cultured embryonic mouse kidney. Int J Dev Biol 46:1049–1055

    PubMed  Google Scholar 

  • Davies JA (2002) Do different branching epithelia use a conserved developmental mechanism? Bioessays 24:937–948

    Article  PubMed  Google Scholar 

  • Donjacour AA, Cunha GR (1988) The effect of androgen deprivation on branching morphogenesis in the mouse prostate. Dev Biol 128:1–14

    Article  PubMed  Google Scholar 

  • Durbeej M, Ekblom P (1997) Dystroglycan and laminins: glycoconjugates involved in branching epithelial morphogenesis. Exp Lung Res 23:109–118

    PubMed  Google Scholar 

  • Fisher CE, Michael L, Barnett MW, Davies JA (2001) Erk MAP kinase regulates branching morphogenesis in the developing mouse kidney. Development 128:4329–4338

    PubMed  Google Scholar 

  • Fricout G, Cullen-McEwen L, Harper IS, Jeulin D, Bertram JF (2001) A quantitative method for analysing 3D branching in embryonic kidneys: development of a technique and preliminary data. Image Anal Stereol 20:36–41

    Google Scholar 

  • Gill WB, Schumacher GF, Bibbo M, Straus FH II, Schoenberg HW (1979) Association of diethylstilbestrol exposure in utero with cryptorchidism, testicular hypoplasia and semen abnormalities. J Urol 122:36–39

    PubMed  Google Scholar 

  • Harris SE, Harris MA, Mahy P, Wozney J, Feng JQ, Mundy GR (1994) Expression of bone morphogenetic protein messenger RNAs by normal rat and human prostate and prostate cancer cells. Prostate 24:204–211

    PubMed  Google Scholar 

  • Hayashi N, Sugimura Y, Kawamura J, Donjacour AA, Cunha GR (1991) Morphological and functional heterogeneity in the rat prostatic gland. Biol Reprod 45:308–321

    Article  PubMed  Google Scholar 

  • Herbst AL, Ulfelder H, Poskanzer DC (1971) Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med 284:878–881

    PubMed  Google Scholar 

  • Hogan BL (1999) Morphogenesis. Cell 96:225–233

    PubMed  Google Scholar 

  • Howdeshell KL, Hotchkiss AK, Thayer KA, Vandenburgh JG, Saal FS vom (1999) Exposure to bisphenol A advances puberty. Nature 401:763–764

    Article  PubMed  Google Scholar 

  • Jung HS, Francis-West PH, Widelitz RB, Jiang TX, Ting-Berreth S, Tickle C, Wolpert L, Chuong CM (1998) Local inhibitory action of BMPs and their relationships with activators in feather formation: implications for periodic patterning. Dev Biol 196:11–23

    PubMed  Google Scholar 

  • Ko K, Theobald HM, Peterson RE (2002) In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in the C57BL/6J mouse prostate: lobe-specific effects on branching morphogenesis. Toxicol Sci 70:227–237

    Article  PubMed  Google Scholar 

  • Krasnow MA, Nelson WJ (2002) Tube morphogenesis. Trends Cell Biol 12:351

    Article  PubMed  Google Scholar 

  • Lamm MLG, Podlasek CA, Barnett DH, Lee J, Clemens JQ, Hebner CM, Bushman W (2001) Mesenchymal factor bone morphogenetic protein 4 restricts ductal budding and branching morphogenesis in the developing prostate. Dev Biol 232:301–314

    PubMed  Google Scholar 

  • Larsen M, Hoffman MP, Sakai T, Neibaur JC, Mitchell JM, Yamada KM (2003) Role of PI 3-kinase and PIP3 in submandibular gland branching morphogenesis. Dev Biol 255:178–191

    Article  PubMed  Google Scholar 

  • Lin TM, Rasmussen NT, Moore RW, Albrecht RM, Peterson RE (2003) Region-specific inhibition of prostatic epithelial bud formation in the urogenital sinus of C57BL/6 mice exposed in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Sci 76:171–181

    Article  PubMed  Google Scholar 

  • Marker PC, Stephan JP, Lee J, Bald L, Mather JP, Cunha GR (2001) Fucosyltransferase1 and H-type complex carbohydrates modulate epithelial cell proliferation during prostatic branching morphogenesis. Dev Biol 233:95–108

    Article  PubMed  Google Scholar 

  • Marker PC, Dahiya R, Cunha GR (2003) Spontaneous mutation in mice provides new insight into the genetic mechanisms that pattern the seminal vesicles and prostate gland. Dev Dyn 226:643–653

    Article  PubMed  Google Scholar 

  • McLachlan JA (1977) Prenatal exposure to diethylstilbestrol in mice: toxicological studies. J Toxicol Environ Health 2:527–537

    PubMed  Google Scholar 

  • McNeal JE (1978) Origin and evolution of benign prostatic enlargement. Invest Urol 15:340–345

    PubMed  Google Scholar 

  • Melnick R, Lucier G, Wolfe M, Hall R, Stancel G, Prins G, Gallo M, Reuhl K, Ho SM, Brown T, Moore J, Leakey J, Haseman J, Kohn M (2002) Summary of the National Toxicology Program’s report of the endocrine disruptors low-dose peer review. Environ Health Perspect 110:427–431

    PubMed  Google Scholar 

  • Miyazaki Y, Oshima K, Fogo A, Hogan BL, Ichikawa I (2000) Bone morphogenetic protein 4 regulates the budding site and elongation of the mouse ureter. J Clin Invest 105:863–873

    PubMed  Google Scholar 

  • Naslund MJ, Coffey DS (1986) The differential effects of neonatal androgen, estrogen and progesterone on adult rat prostate growth. J Urol 136:1136–1140

    PubMed  Google Scholar 

  • Piacsek BE, Hostetter MW (1984) Neonatal androgenization in the male rat: evidence for central and peripheral defects. Biol Reprod 30:344–351

    PubMed  Google Scholar 

  • Prins GS (1992) Neonatal estrogen exposure induces lobe-specific alterations in adult rat prostate androgen receptor expression. Endocrinology 130:3703–3714

    Article  PubMed  Google Scholar 

  • Prins GS (1997) Developmental estrogenization of the prostate gland. In: Naz R (ed) Prostate basic and clinical aspects. CRC, New York, pp 245–263

    Google Scholar 

  • Prins GS, Birch L (1995) The developmental pattern of androgen receptor expression in rat prostate lobes is altered after neonatal exposure to estrogen. Endocrinology 136:1303–1314

    Article  PubMed  Google Scholar 

  • Prins GS, Birch L (1997) Neonatal estrogen exposure up-regulates estrogen receptor expression in the developing and adult rat prostate lobes. Endocrinology 138:1801–1809

    Article  PubMed  Google Scholar 

  • Prins GS, Marmer M, Woodham C, Chang W, Kuiper G, Gustafsson JA, Birch L (1998) Estrogen receptor-beta messenger ribonucleic acid ontogeny in the prostate of normal and neonatally estrogenized rats. Endocrinology 139:874–883

    Article  PubMed  Google Scholar 

  • Prins GS, Birch L, Couse JF, Choi I, Katzenellenbogen B, Korach KS (2001) Estrogen imprinting of the developing prostate gland is mediated through stromal estrogen receptor alpha: studies with alphaERKO and betaERKO mice. Cancer Res 61:6089–6097

    PubMed  Google Scholar 

  • Putz O, Schwartz CB, Kim S, LeBlanc GA, Cooper RL, Prins GS (2001) Neonatal low- and high-dose exposure to estradiol benzoate in the male rat. I. Effects on the prostate gland. Biol Reprod 65:1496–1505

    Article  PubMed  Google Scholar 

  • Pylkkanen L, Santti R, Newbold R, McLachlan JA (1991) Regional differences in the prostate of the neonatally estrogenized mouse. Prostate 18:117–129

    PubMed  Google Scholar 

  • Raatikainen-Ahokas A, Hytonen M, Tenhunen A, Sainio K, Sariola H (2000) BMP-4 affects the differentiation of metanephric mesenchyme and reveals an early anterior–posterior axis of the embryonic kidney. Dev Dyn 217:146–158

    Article  PubMed  Google Scholar 

  • Rajfer J, Coffey DS (1978) Sex steroid imprinting of the immature prostate. Long-term effects. Invest Urol 16:186–190

    PubMed  Google Scholar 

  • Rajfer J, Coffey DS (1979) Effects of neonatal steroids on male sex tissues. Invest Urol 17:3–8

    PubMed  Google Scholar 

  • Risbridger GP, Wang H, Frydenberg M, Cunha G (2001) The metaplastic effects of estrogen on mouse prostate epithelium: proliferation of cells with basal cell phenotype. Endocrinology 142:2443–2450

    PubMed  Google Scholar 

  • Roman BL, Timms BG, Prins GS, Peterson RE (1998) In utero and lactational exposure of the male rat to 2,3,7,8-tetrachlorodibenzo-p-dioxin impairs prostate development. 2. Effects on growth and cytodifferentiation. Toxicol Appl Pharmacol 150:254–270

    Article  PubMed  Google Scholar 

  • Ruan W, Powell-Braxton L, Kopchick JJ, Kleinberg DL (1999) Evidence that insulin-like growth factor I and growth hormone are required for prostate gland development. Endocrinology 140:1984–1989

    Article  PubMed  Google Scholar 

  • Saal FS vom (1989) Sexual differentiation in litter-bearing mammals: influence of sex of adjacent fetuses in utero. J Anim Sci 67:1824–1840

    PubMed  Google Scholar 

  • Saal F vom, Montano M, Wang M (1992) Chemically-induced alterations in sexual and functional development: the wildlife/human connection. In: Colburn T, Clement C (eds) Sexual differentiation in mammals. Princeton Scientific, Princeton, pp 17–83

    Google Scholar 

  • Saal FS vom, Timms BG, Montano MM, Palanza P, Thayer KA, Nagel SC, Dhar MD, Ganjam VK, Parmigiani S, Welshons WV (1997) Prostate enlargement in mice due to fetal exposure to low doses of estradiol or diethylstilbestrol and opposite effects at high doses. Proc Natl Acad Sci USA 94:2056–2061

    Article  PubMed  Google Scholar 

  • Singh J, Handelsmann DJ (1999) Imprinting by neonatal sex steroids on the structure and function of the mature mouse prostate. Biol Reprod 61:200–208

    PubMed  Google Scholar 

  • Sugimura Y, Cunha GR, Donjacour AA (1986) Morphogenesis of ductal networks in the mouse prostate. Biol Reprod 34:961–971

    PubMed  Google Scholar 

  • Sugimura Y, Cunha GR, Yonemura CU, Kawamura J (1988) Temporal and spatial factors in diethylstilbestrol-induced squamous metaplasia of the developing human prostate. Human Pathol 19:133–139

    Google Scholar 

  • Thayer KA, Ruhlen RL, Howdeshell KL, Buchanan DL, Cooke PS, Preziosi D, Welshons WV, Haseman J, Saal FS vom (2001) Altered prostate growth and daily sperm production in male mice exposed prenatally to subclinical doses of 17alpha-ethinyl oestradiol. Hum Reprod 16:988–996

    Article  PubMed  Google Scholar 

  • Timms BG, Mohs TJ, Didio LJ (1994) Ductal budding and branching patterns in the developing prostate. J Urol 151:1427–432

    PubMed  Google Scholar 

  • Timms BG, Petersen SL, Saal FS vom (1999) Prostate gland growth during development is stimulated in both male and female rat fetuses by intrauterine proximity to female fetuses. J Urol 161:1694–1701

    Article  PubMed  Google Scholar 

  • Timms BG, Peterson RE, Saal FS vom (2002) 2,3,7,8-Tetrachlorodibenzo-p-dioxin interacts with endogenous estradiol to disrupt prostate gland morphogenesis in male rat fetuses. Toxicol Sci 67:264–274

    Article  PubMed  Google Scholar 

  • Tinwell H, Haseman J, Lefevre PA, Wallis N, Ashby J (2002) Normal sexual development of two strains of rat exposed in utero to low doses of bisphenol A. Toxicol Sci 68:339–348

    Article  PubMed  Google Scholar 

  • Weaver M, Yingling JM, Dunn NR, Bellusci S, Hogan BL (1999) Bmp signaling regulates proximal–distal differentiation of endoderm in mouse lung development. Development 126:4005–4015

    PubMed  Google Scholar 

  • Whitehead ED (1981) DES story; review and report. N Y State J Med 81:869–989

    PubMed  Google Scholar 

  • Whitehead ED, Leiter E (1981) Genital abnormalities and abnormal semen analyses in male patients exposed to diethylstilbestrol in utero. J Urol 125:47–50

    PubMed  Google Scholar 

  • Yonemura CY, Cunha GR, Sugimura Y, Mee SL (1995) Temporal and spatial factors in diethylstilbestrol-induced squamous metaplasia in the developing human prostate. II. Persistent changes after removal of diethylstilbestrol. Acta Anat 153:1–11

    PubMed  Google Scholar 

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Acknowledgements

We thank all the staff and students in the Centre for Urological Research and Monash Department of Anatomy and Cell Biology for their support of this work and for providing illustrations.

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  1. Centre for Urological Research, Monash Institute of Medical Research, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria, 3168, Australia

    G. P. Risbridger, G. A. Almahbobi & R. A. Taylor

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  1. G. P. Risbridger
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  2. G. A. Almahbobi
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  3. R. A. Taylor
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Correspondence to G. P. Risbridger.

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This study is supported by an NH&MRC program grant number 973218.

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Risbridger, G.P., Almahbobi, G.A. & Taylor, R.A. Early prostate development and its association with late-life prostate disease. Cell Tissue Res 322, 173–181 (2005). https://doi.org/10.1007/s00441-005-1121-9

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