PMID- 27663972
OWN - NLM
STAT- MEDLINE
DCOM- 20170510
LR  - 20170510
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Linking)
VI  - 370
DP  - 2016 Aug 31
TI  - In utero methoxychlor exposure increases rat fetal Leydig cell number but 
      inhibits its function.
PG  - 31-40
LID - S0300-483X(16)30215-3 [pii]
LID - 10.1016/j.tox.2016.09.009 [doi]
AB  - The objective of the present study is to determine whether in utero exposure to 
      methoxychlor (MXC) affects rat fetal Leydig cell number, cell size, or functions. 
      Pregnant Sprague Dawley dams were gavaged with corn oil (control, 0mg/kg/day MXC) 
      or MXC at doses of 10, 50, or 100mg/kg/day from gestational day (GD) 12 to 21. 
      The results show that MXC increased fetal Leydig cell numbers dose-dependently 
      from 95+/-8x10(3) cells/testis (control, mean+/-SEM) to 101+/-6, 148+/-22, and 
      168+/-21x10(3) cells/testis, at the doses of 10, 50, and 100mg/kg, respectively. 
      The increase of Leydig cell number by MXC was contributed by the increase of 
      single cell population of Leydig cells, which increased from 21+/-2% of the control 
      to 31+/-4%, 39+/-3%, or 40+/-4% at the doses of 10, 50 or 100mg/kg, respectively. 
      Quantitative PCR results show that MXC increased Lhcgr expression at dose of 
      10mg/kg and Scarb1 and Cyp11a1 mRNA levels at doses of 50 and 100mg/kg. 
      Immunohistochemical staining demonstrated the increase of CYP11A1 protein level 
      from the dose of 10mg/kg. However, at the highest dose (100mg/kg) MXC reduced the 
      testicular testosterone level and MXC (1muM) in vitro treatment also inhibited 
      androgen production from isolated fetal Leydig cells. In conclusion, our findings 
      indicate that at low dose MXC may increase fetal Leydig cell numbers and the 
      expressions of some steroidogenic enzymes, but at high dose it reduces the 
      testicular testosterone level leading to reproductive tract malformations in the 
      male offspring.
CI  - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved.
FAU - Liu, Shiwen
AU  - Liu S
AD  - Department of Anesthesiology, The 2nd Affiliated Hospital, Wenzhou Medical 
      University, Wenzhou, Zhejiang 325027, China.
FAU - Li, Chao
AU  - Li C
AD  - Center for Scientific Research, The 2nd Affiliated Hospital, Wenzhou Medical 
      University, Wenzhou, Zhejiang 325027, China.
FAU - Wang, Yiyan
AU  - Wang Y
AD  - Department of Anesthesiology, The 2nd Affiliated Hospital, Wenzhou Medical 
      University, Wenzhou, Zhejiang 325027, China.
FAU - Hong, Tingting
AU  - Hong T
AD  - Center for Scientific Research, The 2nd Affiliated Hospital, Wenzhou Medical 
      University, Wenzhou, Zhejiang 325027, China.
FAU - Song, Tiantian
AU  - Song T
AD  - Department of Anesthesiology, The 2nd Affiliated Hospital, Wenzhou Medical 
      University, Wenzhou, Zhejiang 325027, China.
FAU - Li, Linxi
AU  - Li L
AD  - Center for Scientific Research, The 2nd Affiliated Hospital, Wenzhou Medical 
      University, Wenzhou, Zhejiang 325027, China.
FAU - Ye, Leping
AU  - Ye L
AD  - Department of Pediatrics, The 2nd Affiliated Hospital, Wenzhou Medical 
      University, Wenzhou, Zhejiang 325027, China.
FAU - Lian, Qingquan
AU  - Lian Q
AD  - Department of Anesthesiology, The 2nd Affiliated Hospital, Wenzhou Medical 
      University, Wenzhou, Zhejiang 325027, China.
FAU - Ge, Ren-Shan
AU  - Ge RS
AD  - Department of Anesthesiology, The 2nd Affiliated Hospital, Wenzhou Medical 
      University, Wenzhou, Zhejiang 325027, China. Electronic address: r_ge@yahoo.com.
LA  - eng
PT  - Journal Article
DEP - 20160920
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Androgens)
RN  - 0 (RNA, Messenger)
RN  - 3XMK78S47O (Testosterone)
RN  - EC 1.14.15.6 (Cholesterol Side-Chain Cleavage Enzyme)
RN  - RIA79UD69L (Methoxychlor)
SB  - IM
MH  - Androgens/metabolism
MH  - Animals
MH  - Cell Count
MH  - Cholesterol Side-Chain Cleavage Enzyme/genetics/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Fetus/drug effects/metabolism
MH  - Image Processing, Computer-Assisted
MH  - Leydig Cells/*drug effects/metabolism
MH  - Male
MH  - Maternal Exposure/*adverse effects
MH  - Methoxychlor/*toxicity
MH  - Pregnancy
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reproduction/drug effects
MH  - Testis/drug effects/metabolism
MH  - Testosterone/metabolism
OTO - NOTNLM
OT  - Cell number
OT  - Fetal Leydig cells
OT  - Methoxychlor
OT  - Steroidogenesis
EDAT- 2016/10/25 06:00
MHDA- 2017/05/11 06:00
CRDT- 2016/09/25 06:00
PHST- 2016/06/22 00:00 [received]
PHST- 2016/09/17 00:00 [revised]
PHST- 2016/09/19 00:00 [accepted]
PHST- 2016/10/25 06:00 [pubmed]
PHST- 2017/05/11 06:00 [medline]
PHST- 2016/09/25 06:00 [entrez]
AID - S0300-483X(16)30215-3 [pii]
AID - 10.1016/j.tox.2016.09.009 [doi]
PST - ppublish
SO  - Toxicology. 2016 Aug 31;370:31-40. doi: 10.1016/j.tox.2016.09.009. Epub 2016 Sep 
      20.