PMID- 32662666
OWN - NLM
STAT- MEDLINE
DCOM- 20210422
LR  - 20210422
IS  - 1477-0903 (Electronic)
IS  - 0960-3271 (Linking)
VI  - 39
IP  - 12
DP  - 2020 Dec
TI  - Role of unfolded protein response in genital malformation/damage of male mice 
      induced by flutamide.
PG  - 1690-1699
LID - 10.1177/0960327120937049 [doi]
AB  - The unfolded protein response (UPR) is one of a switch of autophagy and 
      apoptosis, and the endoplasmic reticulum stress (ERS) which inducing UPR plays a 
      role in the malformations caused by some genetic and environmental factors. 
      Exposure to flutamide during pregnancy will also cause abnormalities in some male 
      offspring reproductive organs such as cryptorchidism. In this study, after 
      administered the pregnant mouse orally at a dose of 300 mg/kg body weight every 
      day during gestational day (GD)12 to GD18, flutamide can not only caused 
      hypospadias in the male mouse offspring but also damaged the morphology and 
      function of their testis. And the expression of UPR-related genes and proteins, 
      autophagy, apoptosis, and angiogenesis-related genes of the damaged/teratogenic 
      testis and penis in the mice were investigated to determine the role of UPR in 
      this model. It was found that flutamide activated maybe the Atg7-Atg3-Lc3 pathway 
      through the UPR pathway, caused cells excessive autophagy and apoptosis, and 
      inhibited the formation of penile and testicular blood vessels by activating UPR 
      and affecting the messenger RNA level of vascular endothelial growth factor and 
      hypoxia-inducible factor 1.
FAU - Yu, H
AU  - Yu H
AD  - Department of Critical Medicine, 12568the First Affiliated Hospital of Hunan 
      Normal University/the People's Hospital of Hunan Province, Changsha, People's 
      Republic of China.
FAU - Wen, K
AU  - Wen K
AD  - Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan 
      Province, Medical School, 12568Hunan Normal University, Changsha, People's 
      Republic of China.
AD  - Changsha Center for Disease Control and Prevention of Hunan Province, Changsha, 
      People's Republic of China.
FAU - Zhou, X
AU  - Zhou X
AD  - Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan 
      Province, Medical School, 12568Hunan Normal University, Changsha, People's 
      Republic of China.
FAU - Zhang, Y
AU  - Zhang Y
AD  - Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan 
      Province, Medical School, 12568Hunan Normal University, Changsha, People's 
      Republic of China.
FAU - Yan, Z
AU  - Yan Z
AD  - Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan 
      Province, Medical School, 12568Hunan Normal University, Changsha, People's 
      Republic of China.
FAU - Fu, H
AU  - Fu H
AD  - Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan 
      Province, Medical School, 12568Hunan Normal University, Changsha, People's 
      Republic of China.
FAU - Zhu, J
AU  - Zhu J
AD  - Department of Health Toxicology, Naval Military Medical University, Shanghai, 
      People's Republic of China.
FAU - Zhu, Y
AU  - Zhu Y
AUID- ORCID: 0000-0002-8722-6445
AD  - Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan 
      Province, Medical School, 12568Hunan Normal University, Changsha, People's 
      Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20200714
PL  - England
TA  - Hum Exp Toxicol
JT  - Human & experimental toxicology
JID - 9004560
RN  - 0 (Androgen Antagonists)
RN  - 0 (Teratogens)
RN  - 76W6J0943E (Flutamide)
SB  - IM
MH  - Androgen Antagonists/*toxicity
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Autophagy/drug effects
MH  - Female
MH  - Flutamide/*toxicity
MH  - Gene Expression/drug effects
MH  - Male
MH  - Mice, Inbred ICR
MH  - Penis/abnormalities/*drug effects/metabolism/pathology
MH  - Pregnancy
MH  - Teratogens/*toxicity
MH  - Testis/abnormalities/*drug effects/metabolism/pathology
MH  - Unfolded Protein Response/*drug effects/genetics
OTO - NOTNLM
OT  - Unfolded protein response
OT  - damage
OT  - flutamide
OT  - male genital
OT  - malformation
EDAT- 2020/07/15 06:00
MHDA- 2021/04/23 06:00
CRDT- 2020/07/15 06:00
PHST- 2020/07/15 06:00 [pubmed]
PHST- 2021/04/23 06:00 [medline]
PHST- 2020/07/15 06:00 [entrez]
AID - 10.1177/0960327120937049 [doi]
PST - ppublish
SO  - Hum Exp Toxicol. 2020 Dec;39(12):1690-1699. doi: 10.1177/0960327120937049. Epub 
      2020 Jul 14.