title: Sertoli cell development and function in an animal model of testicular dysgenesis syndrome.
abstract: Pregnancy exposure to di(n-butyl) phthalate (DBP) in rats induces a testicular dysgenesislike syndrome (TDS) in male offspring. Earlier studies suggested altered Sertoli cell development/maturation may result, especially in testes that become cryptorchid. This study quantitatively assessed Sertoli cell numerical and functional development in DBP-exposed rats and compared (unilaterally) cryptorchid and scrotal testes. Pregnant rats were gavaged with 500 mg/kg/day DBP or corn oil from embryonic (E) Days 13.5 to 21.5. Male offspring were sampled on E21.5 or Postnatal Day 6, 10, 15, 25, or 90. Sertoli cell number in DBP-exposed males was reduced by approximately 50% at E21.5 but recovered to normal by Days 25-90, accompanied by significant changes in plasma inhibin B and testosterone levels. Sertoli cell maturational development in DBP-exposed males, assessed using five protein markers (anti-müllerian hormone, cytokeratin, androgen receptor, CDKN1B, and Nestin), was largely normal, with some evidence of delayed maturation. However, in adulthood, Sertoli cells (SC) in areas lacking germ cells (Sertoli cell-only [SCO] tubules) often exhibited immature features, especially in cryptorchid testes. Sertoli cells in DBP-exposed animals supported fewer germ cells during puberty, but this normalized in scrotal testes by adulthood. Scrotal and especially cryptorchid testes from DBP-exposed animals exhibited abnormalities (SCO tubules, focal dysgenetic areas) at all postnatal ages. Cryptorchid testes from DBP-exposed animals exhibited more Sertoli cell abnormalities at Day 25 compared with scrotal testes, perhaps indicating more severe underlying Sertoli cell malfunction in these testes. Our findings support the concept of altered Sertoli cell development in TDS, especially in cryptorchid testes, but show that maturational defects in Sertoli cells in adulthood most commonly reflect secondary dedifferentiation in absence of germ cells.
authors.affiliation: Medical Research Council Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Hutchison
authors.forename: Hayley M
authors.initials: HM
authors.lastname: Scott
authors.forename: Marion
authors.initials: M
authors.lastname: Walker
authors.forename: Chris
authors.initials: C
authors.lastname: McKinnell
authors.forename: Diana
authors.initials: D
authors.lastname: Ferrara
authors.forename: I Kim
authors.initials: IK
authors.lastname: Mahood
authors.forename: Richard M
authors.initials: RM
authors.lastname: Sharpe
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002452:Cell Count; D003456:Cryptorchidism / Q000139:chemically induced / Q000473:pathology*; D003993:Dibutyl Phthalate / Q000633:toxicity; D004195:Disease Models, Animal; D005640:Follicle Stimulating Hormone / Q000097:blood; D006059:Gonadal Dysgenesis / Q000139:chemically induced / Q000473:pathology*; D007265:Inhibins / Q000097:blood; D008297:Male; D009929:Organ Size; D010968:Plasticizers / Q000633:toxicity; D011506:Proteins / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012708:Sertoli Cells / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D013093:Spermatogonia / Q000166:cytology / Q000502:physiology; D013577:Syndrome; D013737:Testis / Q000002:abnormalities* / Q000473:pathology*; D013739:Testosterone / Q000097:blood
chemical_list: D015415:Biomarkers; D010968:Plasticizers; D011506:Proteins; D003993:Dibutyl Phthalate; D013739:Testosterone; D007265:Inhibins; D005640:Follicle Stimulating Hormone