Comparative Effects of Di(n-Butyl) Phthalate Exposure on Fetal Germ Cell Development in the Rat and in Human Fetal Testis Xenografts.
Background: Phthalate exposure induces germ cell effects in the fetal rat testis. Although experimental models have shown that the human fetal testis is insensitive to the steroidogenic effects of phthalates, the effects on germ cells have been less explored. Objectives: We sought to identify the ef...
| Publicado en: | Environmental Health Perspectives Vol. 123; no. 3; pp. 223 - 231 |
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| Autores principales: | , , , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
National Institute of Environmental Health Sciences
Mar2015
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=103766846&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 103766846 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00916765 3B5 jtl: Environmental Health Perspectives issn: 00916765 maglogo: N pubinfo: dt: Mar2015 vid: 123 iid: 3 pid: 56539 pub: National Institute of Environmental Health Sciences place: Research Triangle Park, North Carolina artinfo: ui: 103766846 101312864 10.1289/ehp.1408248 103766846 ppf: 223 ppct: 8 formats: fmt: @attributes: type: P tig: atl: Comparative Effects of Di(n-Butyl) Phthalate Exposure on Fetal Germ Cell Development in the Rat and in Human Fetal Testis Xenografts. aug: au: Driesche, Sander Van Den McKinnell, Chris Calarrão, Ana Kennedy, Laura Hutchison, Gary R. Hrabalkova, Lenka Jobling, Matthew S. Macpherson, Sheila Anderson, Richard A. Sharpe, Richard M. Mitchell, Rod T. affil: Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom sug: subj: Acids, Carbocyclic Adverse Effects Germ Cells Drug Effects Testis Drug Effects Xenografts Human Animal Studies Rats Immunohistochemistry Polymerase Chain Reaction Fluorescent Antibody Technique Cell Culture Techniques Descriptive Statistics Data Analysis Software One-Way Analysis of Variance Post Hoc Analysis Gene Expression T-Tests Funding Source ab: Background: Phthalate exposure induces germ cell effects in the fetal rat testis. Although experimental models have shown that the human fetal testis is insensitive to the steroidogenic effects of phthalates, the effects on germ cells have been less explored. Objectives: We sought to identify the effects of phthalate exposure on human fetal germ cells in a dynamic model and to establish whether the rat is an appropriate model for investigating such effects. Methods: We used immunohistochemistry, immunofluorescence, and quantitative real-time polymerase chain reaction to examine Sertoli and germ cell markers on rat testes and human fetal testis xenografts after exposure to vehicle or di(n-butyl) phthalate (DBP). Our study included analysis of germ cell differentiation markers, proliferation markers, and cell adhesion proteins. Results: In both rat and human fetal testes, DBP exposure induced similar germ cell effects, namely, germ cell loss (predominantly undifferentiated), induction of multinucleated gonocytes (MNGs), and aggregation of differentiated germ cells, although the latter occurred rarely in the human testes. The mechanism for germ cell aggregation and MNG induction appears to be loss of Sertoli cell–germ cell membrane adhesion, probably due to Sertoli cell microfilament redistribution. Conclusions: Our findings provide the first comparison of DBP effects on germ cell number, differentiation, and aggregation in human testis xenografts and in vivo in rats. We observed comparable effects on germ cells in both species, but the effects in the human were muted compared with those in the rat. Nevertheless, phthalate effects on germ cells have potential implications for the next generation, which merits further study. Our results indicate that the rat is a human-relevant model in which to explore the mechanisms for germ cell effects. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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