title: Cellular and molecular effect of MEHP Involving LXRα in human fetal testis and ovary.
abstract: BACKGROUND
  Phthalates have been shown to have reprotoxic effects in rodents and human during fetal life. Previous studies indicate that some members of the nuclear receptor (NR) superfamilly potentially mediate phthalate effects. This study aimed to assess if expression of these nuclear receptors are modulated in the response to MEHP exposure on the human fetal gonads in vitro.
  
  
  RESULTS
  Testes and ovaries from 7 to 12 gestational weeks human fetuses were exposed to 10(-4)M MEHP for 72 h in vitro. Transcriptional level of NRs and of downstream genes was then investigated using TLDA (TaqMan Low Density Array) and qPCR approaches. To determine whether somatic or germ cells of the testis are involved in the response to MEHP exposure, we developed a highly efficient cytometric germ cell sorting approach. In vitro exposure of fetal testes and ovaries to MEHP up-regulated the expression of LXRα, SREBP members and of downstream genes involved in the lipid and cholesterol synthesis in the whole gonad. In sorted testicular cells, this effect is only observable in somatic cells but not in the gonocytes. Moreover, the germ cell loss induced by MEHP exposure, that we previously described, is restricted to the male gonad as oogonia density is not affected in vitro.
  
  
  CONCLUSIONS
  We evidenced for the first time that phthalate increases the levels of mRNA for LXRα, and SREBP members potentially deregulating lipids/cholesterol synthesis in human fetal gonads. Interestingly, this novel effect is observable in both male and female whereas the germ cell apoptosis is restricted to the male gonad. Furthermore, we presented here a novel and potentially very useful flow cytometric cell sorting method to analyse molecular changes in germ cells versus somatic cells.
authors.affiliation: University Paris Diderot, Sorbonne Paris Cité, Laboratory of Development of the Gonads, Unit of Stem Cells and Radiation, Fontenay-aux-Roses, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Muczynski
authors.forename: Charlotte
authors.initials: C
authors.lastname: Lecureuil
authors.forename: Sébastien
authors.initials: S
authors.lastname: Messiaen
authors.forename: Marie-Justine
authors.initials: MJ
authors.lastname: Guerquin
authors.forename: Thierry
authors.initials: T
authors.lastname: N'tumba-Byn
authors.forename: Delphine
authors.initials: D
authors.lastname: Moison
authors.forename: Wassim
authors.initials: W
authors.lastname: Hodroj
authors.forename: Hinde
authors.initials: H
authors.lastname: Benjelloun
authors.forename: Jan
authors.initials: J
authors.lastname: Baijer
authors.forename: Gabriel
authors.initials: G
authors.lastname: Livera
authors.forename: René
authors.initials: R
authors.lastname: Frydman
authors.forename: Alexandra
authors.initials: A
authors.lastname: Benachi
authors.forename: René
authors.initials: R
authors.lastname: Habert
authors.forename: Virginie
authors.initials: V
authors.lastname: Rouiller-Fabre
mesh_terms: D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000633:toxicity; D004785:Environmental Pollutants / Q000633:toxicity; D005260:Female; D005333:Fetus / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D066298:In Vitro Techniques; D008055:Lipids / Q000096:biosynthesis; D000071518:Liver X Receptors; D008297:Male; D057093:Orphan Nuclear Receptors / Q000235:genetics*; D010053:Ovary / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010063:Ovum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013094:Spermatozoa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013737:Testis / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D004785:Environmental Pollutants; D008055:Lipids; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D004051:Diethylhexyl Phthalate; C016599:mono-(2-ethylhexyl)phthalate