PMID- 31933163
OWN - NLM
STAT- MEDLINE
DCOM- 20201207
LR  - 20201214
IS  - 1933-7205 (Electronic)
IS  - 1933-7191 (Print)
IS  - 1933-7191 (Linking)
VI  - 27
IP  - 3
DP  - 2020 Mar
TI  - Nicotine Suppresses the Invasiveness of Human Trophoblasts by Downregulation of 
      CXCL12 Expression through the Alpha-7 Subunit of the Nicotinic Acetylcholine 
      Receptor.
PG  - 916-924
LID - 10.1007/s43032-019-00095-4 [doi]
AB  - Smoke exposure during pregnancy has detrimental effects upon numerous fetal and 
      neonatal outcomes. Nicotine (the main component of tobacco) has been suggested to 
      affect placental development. During placental development, efficient invasion by 
      trophoblasts is required for establishment of the fetus-maternal circulation. In 
      this study we explored the regulation of trophoblast invasion by nicotine. An 
      immortalized first trimester extravillous trophoblast cell line (HTR-8/SVneo 
      cells) was used for all the experiments, which were treated by nicotine, 
      methyllycaconitine, and C-X-C motif chemokine ligand 12 (CXCL12). Total RNA and 
      protein were used to study the expressions of nicotinic acetylcholine receptors 
      (nAChRs), and transwell assay was used to study invasiveness. Changes of RNA 
      expression due to nicotine treatment were detected by RNA sequence. Level of 
      CXCL12 mRNA was verified by quantitative PCR. We showed that HTR-8/SVneo 
      expressed subunits alpha2-4, alpha7, alpha9, beta1, and beta2 of nAChRs. Nicotine downregulated 
      CXCL12 expression and inhibited trophoblast invasion. Methyllycaconitine, as an 
      antagonist of the alpha7 homopolymer, blocked the inhibitory effect of nicotine. 
      CXCL12 could rescue the nicotine-induced inhibitory effect on invasion of 
      HTR-8/SVneo cells. These results suggest that the alpha7 subunit of the nAChR has 
      important roles in modulating trophoblast invasion through CXCL12.
FAU - Chen, Jing
AU  - Chen J
AD  - Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South 
      China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong 
      Academy of Medical Sciences,School of Medicine, South China University of 
      Technology, Guangzhou, 510080, China.
AD  - Research Department of Medical Science, Guangdong Provincial People's Hospital, 
      Guangzhou, China.
FAU - Qiu, Min
AU  - Qiu M
AD  - Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South 
      China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong 
      Academy of Medical Sciences,School of Medicine, South China University of 
      Technology, Guangzhou, 510080, China.
AD  - Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, 
      Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 
      Guangzhou, 510080, China.
FAU - Huang, Zirui
AU  - Huang Z
AD  - Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South 
      China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong 
      Academy of Medical Sciences,School of Medicine, South China University of 
      Technology, Guangzhou, 510080, China.
AD  - Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, 
      Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 
      Guangzhou, 510080, China.
FAU - Chen, Jimei
AU  - Chen J
AD  - Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South 
      China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong 
      Academy of Medical Sciences,School of Medicine, South China University of 
      Technology, Guangzhou, 510080, China.
AD  - Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, 
      Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 
      Guangzhou, 510080, China.
FAU - Zhou, Chengbin
AU  - Zhou C
AD  - Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South 
      China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong 
      Academy of Medical Sciences,School of Medicine, South China University of 
      Technology, Guangzhou, 510080, China.
FAU - Han, Fengzhen
AU  - Han F
AD  - Department of Obstetrics and Gynecology, Guangdong Provincial People's Hospital, 
      Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
FAU - Qu, Yanji
AU  - Qu Y
AD  - Department of Epidemiology, Guangdong Cardiovascular Institute, Guangdong 
      Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 
      510080, China.
FAU - Wang, Sheng
AU  - Wang S
AD  - Department of Anesthesiology, Guangdong Cardiovascular Institute, Guangdong 
      Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 
      510080, China.
FAU - Zhuang, Jian
AU  - Zhuang J
AD  - Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South 
      China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong 
      Academy of Medical Sciences,School of Medicine, South China University of 
      Technology, Guangzhou, 510080, China. drzhuangjian5413@163.com.
AD  - Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, 
      Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 
      Guangzhou, 510080, China. drzhuangjian5413@163.com.
FAU - Li, Xiaohong
AU  - Li X
AD  - Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South 
      China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong 
      Academy of Medical Sciences,School of Medicine, South China University of 
      Technology, Guangzhou, 510080, China. lixiaohong@gdph.org.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200113
PL  - United States
TA  - Reprod Sci
JT  - Reproductive sciences (Thousand Oaks, Calif.)
JID - 101291249
RN  - 0 (CXCL12 protein, human)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (alpha7 Nicotinic Acetylcholine Receptor)
RN  - 6M3C89ZY6R (Nicotine)
SB  - IM
EIN - Reprod Sci. 2020 Apr;27(4):1087. PMID: 32207098
MH  - Cell Line
MH  - Chemokine CXCL12/*metabolism
MH  - Down-Regulation/*drug effects
MH  - Female
MH  - Humans
MH  - Nicotine/*administration & dosage
MH  - Placentation/drug effects
MH  - Pregnancy
MH  - Trophoblasts/*drug effects/*metabolism
MH  - alpha7 Nicotinic Acetylcholine Receptor/*metabolism
PMC - PMC7077928
OTO - NOTNLM
OT  - CXCL12
OT  - Invasion
OT  - Nicotine
OT  - Trophoblast
OT  - nAChR
COIS- The authors declare that they have no conflict of interest.
EDAT- 2020/01/15 06:00
MHDA- 2020/12/15 06:00
PMCR- 2020/01/13
CRDT- 2020/01/15 06:00
PHST- 2019/05/13 00:00 [received]
PHST- 2019/08/07 00:00 [accepted]
PHST- 2020/01/15 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2020/01/15 06:00 [entrez]
PHST- 2020/01/13 00:00 [pmc-release]
AID - 10.1007/s43032-019-00095-4 [pii]
AID - 95 [pii]
AID - 10.1007/s43032-019-00095-4 [doi]
PST - ppublish
SO  - Reprod Sci. 2020 Mar;27(3):916-924. doi: 10.1007/s43032-019-00095-4. Epub 2020 
      Jan 13.