Perfluorooctanoic acid-induced inhibition of placental prolactin-family hormone and fetal growth retardation in mice.
Perfluorooctanoic acid (PFOA) is a persistent pollutant worldwide and even found in human cord blood and breast milk. Some animal studies have reported that PFOA causes developmental toxicity such as fetal weight loss, but the mechanism is still unclear. This study focused on developmental toxicity of PFOA, particularly impacts of PFOA on placental endocrine function such as placental prolactin (PRL)-family hormone gene expression and fetal growth in mouse. Time-mated CD-1 mice were dosed by gavage with 0, 2, 10 and 25 mg/kg B.W/day of PFOA (n-10) dissolved with de-ionized water from gestational day (GD) 11-16. During treatment, body weight of each pregnant mouse was measured daily. On day 16, caesarean sections were performed and developmental data were observed. Three placentas from three different pregnant mice were assigned to each of the following experiments. The mRNA levels of mouse placental lactogen (mPL)-II, prolactin like protein (mPLP)-E, -F and Pit-1α and β isotype mRNAs, a transacting factor of mPLs and mPLPs genes, were analyzed using northern blot, in situ hybridization and RT-PCR, respectively. Maternal body weight gain was significantly declined from GD 13 in the PFOA treated groups compared to control. Developmental data such as fetal and placental weights were significantly decreased in accordance with PFOA dosage. Number of dead fetuses and post-implantation losses were significantly increased in the PFOA-exposed groups. In addition, placental efficiency (fetal weight/placental weight) was significantly reduced in PFOA treated groups in accordance with PFOA dosage. Histopathologic changes were observed in placenta. Dose dependent necrotic changes were observed in both 10 mg and 25 mg PFOA treated groups. Cell frequency of glycogen trophoblast cell and parietal trophoblast giant cell were decreased dose dependently in the junctional zone. In the labyrinth zone, sinusoidal trophoblast giant cell frequency was decreased in the 25 mg PFOA treated group. Also, morphological change such as crushed nuclear (atrophy) of trophoblast cells was observed in 25 mg PFOA treated group. Finally, mRNA levels of the mPL-II, mPLP-E, -F and Pit-1α and β were significantly reduced in the PFOA treated groups dose dependently. In addition, the changing pattern between mPL-II, mPLP-E, -F mRNA levels and fetal body weight showed positive relationship. In conclusion, the inhibitory effects of PFOA on the placental prolactin-family hormone genes expression may be secondary effects to insufficient trophoblast cell type differentiation and/or increased trophoblast cell necrosis. The impacts of PFOA on placental development and endocrine function reduced the placental efficiency and partly contributed to the fetal growth retardation in the mouse.
Institute of Environmental and Occupational Medicine & Department of Occupational and Environmental Medicine, College of Medicine, Inje University, South Korea.
Chun Hui
CH
Suh
Nam Kyoo
NK
Cho
Chae Kwan
CK
Lee
Chang Hee
CH
Lee
Dae Hwan
DH
Kim
Jeong Ho
JH
Kim
Byung Chul
BC
Son
Jong Tae
JT
Lee
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002210:Caprylates / Q000009:adverse effects*; D002452:Cell Count; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D005317:Fetal Growth Retardation / Q000139:chemically induced*; D020567:Fetal Weight / Q000187:drug effects; D005466:Fluorocarbons / Q000009:adverse effects*; D051379:Mice; D010920:Placenta / Q000187:drug effects / Q000473:pathology; D010926:Placental Hormones / Q000037:antagonists & inhibitors*; D010928:Placental Lactogen / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism; D050817:Transcription Factor Pit-1 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects
D002210:Caprylates; D016207:Cytokines; D005466:Fluorocarbons; D010926:Placental Hormones; D010928:Placental Lactogen; D011257:Pregnancy Proteins; D050817:Transcription Factor Pit-1; C494185:Pou1f1 protein, mouse; C423011:Prlpe protein, mouse; C502151:Prlpf protein, mouse; C023036:perfluorooctanoic acid