title: Exposure to di(2-ethyl-hexyl) phthalate (DEHP) in utero and during lactation causes long-term pituitary-gonadal axis disruption in male and female mouse offspring.
abstract: The present study examined the effects in mice of exposure to di(2-ethyl-hexyl) phthalate (DEHP) throughout pregnancy and lactation on the development and function of the pituitary-gonadal axis in male and female offspring once they have attained adulthood. Groups of two to three dams were exposed with the diet from gestational d 0.5 until the end of lactation, at 0, 0.05, 5, and 500 mg DEHP/kg · d. The experiment was repeated three times (total: seven to 10 dams per treatment). The 500-mg dose caused complete pregnancy failure, whereas exposure to doses of 0.05 and 5 mg did not affect pregnancy and litter size. In total, about 30 male and 30 female offspring per group were analyzed. Offspring of the DEHP-treated groups, compared with controls, at sexual maturity showed: 1) lower body weight (decrease 20-25%, P < 0.001); 2) altered gonad weight (testes were ∼13% lighter and ovaries ∼40% heavier; P < 0.001); 3) poor germ cell quality (semen was ∼50% less concentrated and 20% less viable, and ∼10% fewer oocytes reached MII stage, P < 0.001); 4) significant lower expression of steroidogenesis and gonadotropin-receptor genes in the gonads; and 5) up-regulated gonadotropin subunit gene expression in the pituitary. In conclusion, our findings suggest that, in maternally exposed male and female mice, DEHP acts on multiple pathways involved in maintaining steroid homeostasis. Specifically, in utero and lactational DEHP exposure may alter estrogen synthesis in both sexes. This, in turn, induces dysregulation of pituitary-gonadal feedback and alters the reproductive performance of exposed animals.
authors.affiliation: Dipartimento di Patologia Animale, Igiene e Sanità Pubblica Veterinaria-Facoltà di Medicina Veterinaria-Università degli Studi di Milano, Via Celoria 10, 20133 Milano, Italy. paola.pocar@unimi.it
authors.forename: Paola
authors.initials: P
authors.lastname: Pocar
authors.forename: Nadia
authors.initials: N
authors.lastname: Fiandanese
authors.forename: Camillo
authors.initials: C
authors.lastname: Secchi
authors.forename: Anna
authors.initials: A
authors.lastname: Berrini
authors.forename: Bernd
authors.initials: B
authors.lastname: Fischer
authors.forename: Juliane S
authors.initials: JS
authors.lastname: Schmidt
authors.forename: Kristina
authors.initials: K
authors.lastname: Schaedlich
authors.forename: Vitaliano
authors.initials: V
authors.lastname: Borromeo
mesh_terms: D000818:Animals; D004051:Diethylhexyl Phthalate / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D046149:Embryo Culture Techniques; D005260:Female; D005307:Fertilization in Vitro; D059471:In Vitro Oocyte Maturation Techniques; D007774:Lactation; D008297:Male; D051379:Mice; D010053:Ovary / Q000187:drug effects* / Q000502:physiology; D010902:Pituitary Gland / Q000187:drug effects* / Q000502:physiology; D010968:Plasticizers / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011297:Prenatal Exposure Delayed Effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000187:drug effects* / Q000502:physiology
chemical_list: D010968:Plasticizers; D004051:Diethylhexyl Phthalate