PMID- 34508824
OWN - NLM
STAT- MEDLINE
DCOM- 20211227
LR  - 20211227
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Linking)
VI  - 462
DP  - 2021 Oct
TI  - Triadimefon suppresses fetal adrenal gland development after in utero exposure.
PG  - 152932
LID - S0300-483X(21)00255-9 [pii]
LID - 10.1016/j.tox.2021.152932 [doi]
AB  - Triadimefon is a broad-spectrum antifungal agent, which is widely used in 
      agriculture to control mold and fungal infections. It is considered an endocrine 
      disruptor. Whether triadimefon exposure can inhibit the development of fetal 
      adrenal glands and the underlying mechanism remain unclear. Thirty-two pregnant 
      female Sprague-Dawley rats were randomly divided into four groups. Dams were 
      gavaged triadimefon (0, 25, 50, and 100 mg/kg/day) daily for 10 days from 
      gestational day (GD) 12 to GD 21. Triadimefon significantly reduced the thickness 
      of the zona fasciculata of male fetuses at 100 mg/kg, although it did not change 
      the thickness of the zona glomerulosa. It significantly reduced the serum 
      aldosterone levels of male fetuses at a dose of 100 mg/kg, and significantly 
      reduced serum corticosterone and adrenocorticotropic hormone levels at doses of 
      50 and 100 mg/kg. Triadimefon significantly down-regulated the expression of 
      Agtr1, Mc2r, Star, Cyp11b1, Cyp11b2, Igf1, Nr5a1, Sod2, Gpx1, and Cat, but did 
      not affect the mRNA levels of Scarb1, Cyp11a1, Cyp21, Hsd3b1, and Hsd11b2. 
      Triadimefon markedly reduced AT1R, CYP11B2, IGF1, NR5A1, and MC2R protein levels. 
      Triadimefon significantly reduced the phosphorylation of AKT1 and ERK1/2 at 100 
      mg/kg without affecting the phosphorylation of AKT2. In contrast, it 
      significantly increased AMPK phosphorylation at 100 mg/kg. In conclusion, 
      exposure to triadimefon during gestation inhibits the development of fetal 
      adrenal cortex in male fetuses. This inhibition is possibly due to the reduction 
      of several proteins required for the synthesis of steroid hormones, and may be 
      involved in changes in antioxidant contents and the phosphorylation of AKT1, 
      ERK1/2, and AMPK.
CI  - Copyright (c) 2021. Published by Elsevier B.V.
FAU - Xu, Qiang
AU  - Xu Q
AD  - Department of Pathology, The Second Affiliated Hospital and Yuying Children's 
      Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
FAU - Chen, Quanxu
AU  - Chen Q
AD  - Department of Pathology, The Second Affiliated Hospital and Yuying Children's 
      Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
FAU - Lin, Liben
AU  - Lin L
AD  - Department of Pathology, The Second Affiliated Hospital and Yuying Children's 
      Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
FAU - Zhang, Pu
AU  - Zhang P
AD  - Department of Pathology, The Second Affiliated Hospital and Yuying Children's 
      Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
FAU - Li, Zengqiang
AU  - Li Z
AD  - Department of Anesthesiology, the Second Affiliated Hospital and Yuying 
      Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
FAU - Yu, Yige
AU  - Yu Y
AD  - Department of Anesthesiology, the Second Affiliated Hospital and Yuying 
      Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
FAU - Ma, Feifei
AU  - Ma F
AD  - Department of Anesthesiology, the Second Affiliated Hospital and Yuying 
      Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
FAU - Ying, Yingfen
AU  - Ying Y
AD  - Department of Obstetrics and Gynecology, the Second Affiliated Hospital and 
      Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
FAU - Li, Xiaoheng
AU  - Li X
AD  - Department of Anesthesiology, the Second Affiliated Hospital and Yuying 
      Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
FAU - Ge, Ren-Shan
AU  - Ge RS
AD  - Department of Anesthesiology, the Second Affiliated Hospital and Yuying 
      Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China. 
      Electronic address: r_ge@yahoo.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210909
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Antioxidants)
RN  - 0 (Endocrine Disruptors)
RN  - 0 (Fungicides, Industrial)
RN  - 0 (Triazoles)
RN  - 1HW039CJF0 (triadimefon)
SB  - IM
MH  - Adrenal Cortex/drug effects/embryology
MH  - Adrenal Glands/*drug effects/embryology
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Endocrine Disruptors/administration & dosage/toxicity
MH  - Female
MH  - Fungicides, Industrial/administration & dosage/*toxicity
MH  - Male
MH  - Maternal Exposure/*adverse effects
MH  - Phosphorylation/drug effects
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Triazoles/administration & dosage/*toxicity
OTO - NOTNLM
OT  - Adrenal development
OT  - Antioxidants
OT  - Fungicide
OT  - Steroidogenesis
OT  - Triadimefon
EDAT- 2021/09/12 06:00
MHDA- 2021/12/28 06:00
CRDT- 2021/09/11 20:10
PHST- 2021/03/04 00:00 [received]
PHST- 2021/08/19 00:00 [revised]
PHST- 2021/09/06 00:00 [accepted]
PHST- 2021/09/12 06:00 [pubmed]
PHST- 2021/12/28 06:00 [medline]
PHST- 2021/09/11 20:10 [entrez]
AID - S0300-483X(21)00255-9 [pii]
AID - 10.1016/j.tox.2021.152932 [doi]
PST - ppublish
SO  - Toxicology. 2021 Oct;462:152932. doi: 10.1016/j.tox.2021.152932. Epub 2021 Sep 9.