title: Maternal Fenvalerate Exposure Induces Fetal Intrauterine Growth Restriction Through Disrupting Placental Thyroid Hormone Receptor Signaling.
abstract: Fenvalerate is an environmental endocrine disruptor that disrupts testosterone and estradiol synthesis. Nevertheless, whether fenvalerate disturbs placental TR signaling remains unclear. The aim of this study was to investigate whether maternal fenvalerate exposure causes fetal intrauterine growth restriction (IUGR) and to explore the role of placental thyroid hormone receptor (TR) signaling. Pregnant mice except controls were orally administered to fenvalerate (0.2, 2.0, or 20 mg/kg) daily throughout pregnancy. As expected, fetal weight was lowered in dams that were administered with 20.0 mg/kg of fenvalerate. Moreover, the rate of IUGR was elevated not only in male fetuses but also in female fetuses of dams exposed to 20.0 mg/kg of fenvalerate. Histopathology showed that the internal space of blood vessels in the labyrinth layer was smaller in placentas of mice exposed to fenvalerate. Mechanistic study found no significant difference on TT4 level in maternal serum, although TT3 level in maternal serum was slightly reduced in dams exposed to 2.0 mg/kg of fenvalerate. Interestingly, placental TRα1 and TRβ1 mRNAs were reduced in mice exposed to fenvalerate. Moreover, nuclear translocation of placental TRβ1 was suppressed in fenvalerate-exposed mice. Further analysis showed that placental Vegfα and Igf2, several target genes of TR signaling, were down-regulated in fenvalerate-exposed mice. In addition, mRNA level of placental CD36, Snat1, and Snat2, 3 nutrient transporters, were reduced in fenvalerate-exposed mice. These results suggest that maternal fenvalerate exposure induces fetal IUGR through disrupting placental TR signaling. These results provide a novel mechanistic explanation for fenvalerate-induced fetal IUGR.
authors.affiliation: Department of Maternal, Child, & Adolescent Health, Anhui Medical University, Hefei, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Maternal, Child, & Adolescent Health, Anhui Medical University, Hefei, China.
authors.forename: Ji-Jie
authors.initials: JJ
authors.lastname: Liu
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Maternal, Child, & Adolescent Health, Anhui Medical University, Hefei, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Fu
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei, China.
authors.forename: Ru
authors.initials: R
authors.lastname: Shen
authors.affiliation: Department of Maternal, Child, & Adolescent Health, Anhui Medical University, Hefei, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Histology and Embryology, Anhui Medical University, Hefei, China.
authors.forename: Yuan-Hua
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Maternal, Child, & Adolescent Health, Anhui Medical University, Hefei, China.|mengxiuhong@163.com
authors.forename: Xiu-Hong
authors.initials: XH
authors.lastname: Meng
authors.affiliation: Department of Toxicology, Anhui Medical University, Hefei, China.|xudex@126.com. Tel.: +86 551 65167923. Fax: +86 551 65161179.
authors.forename: De-Xiang
authors.initials: DX
authors.lastname: Xu
mesh_terms: D000818:Animals; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005317:Fetal Growth Retardation / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D008813:Mice, Inbred ICR; D009570:Nitriles / Q000633:toxicity*; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011256:Pregnancy Outcome; D011722:Pyrethrins / Q000633:toxicity*; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D015398:Signal Transduction; D013963:Thyroid Hormones / Q000097:blood
chemical_list: D052244:Endocrine Disruptors; D009570:Nitriles; D011722:Pyrethrins; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; C017690:fenvalerate
keywords: endocrine disruption; fenvalerate; intrauterine growth restriction (IUGR); thyroid hormone receptors (TRs)