PMID- 31167229
OWN - NLM
STAT- MEDLINE
DCOM- 20200929
LR  - 20200929
IS  - 1529-7268 (Electronic)
IS  - 0006-3363 (Linking)
VI  - 101
IP  - 2
DP  - 2019 Aug 1
TI  - Upregulation of AREG, EGFR, and HER2 contributes to increased VEGF expression in 
      granulosa cells of patients with OHSSdagger.
PG  - 426-432
LID - 10.1093/biolre/ioz091 [doi]
AB  - Ovarian hyperstimulation syndrome (OHSS) is a serious iatrogenic complication in 
      women undergoing induction of ovulation with human chorionic gonadotropin (hCG) 
      for assisted reproductive techniques. Amphiregulin (AREG) is the most abundant 
      epidermal growth factor receptor (EGFR) ligand expressed in human granulosa cells 
      and follicular fluid and can be upregulated by luteinizing hormone (LH)/hCG. 
      However, whether the expression levels of AREG, EGFR, and HER2 change in the 
      granulosa cells of OHSS patients remains unknown. If it does, whether these 
      molecules are involved in the development of OHSS requires investigation. In the 
      present study, we showed that AREG, EGFR, and HER2 transcripts in granulosa cells 
      as well as follicular fluid AREG proteins were elevated in OHSS patients. 
      Increased AREG levels were associated with transcript levels and follicular 
      content of vascular endothelial growth factor (VEGF), the marker for OHSS 
      pathology. Treatment of cultured granulosa cells with AREG stimulated VEGF 
      expression and secretion, with granulosa cells from OHSS patients showing more 
      rapid and pronounced increases than the non-OHSS group. In addition, 
      siRNA-mediated knockdown of EGFR and AREG attenuated the hCG-induced upregulation 
      of VEGF. This study demonstrated that granulosa cell-secreted AREG plays an 
      important role in the development of OHSS, suggesting that the EGFR/HER2-mediated 
      signaling could be a novel drug target for the prevention and treatment of OHSS.
CI  - (c) The Author(s) 2019. Published by Oxford University Press on behalf of Society 
      for the Study of Reproduction.
FAU - Fang, Lanlan
AU  - Fang L
AD  - Reproductive Medical Center, The First Affiliated Hospital of Zhengzhou 
      University, Zhengzhou, China.
FAU - Yu, Yiping
AU  - Yu Y
AD  - Reproductive Medical Center, The First Affiliated Hospital of Zhengzhou 
      University, Zhengzhou, China.
FAU - Li, Yiran
AU  - Li Y
AD  - Reproductive Medical Center, The First Affiliated Hospital of Zhengzhou 
      University, Zhengzhou, China.
FAU - Wang, Sijia
AU  - Wang S
AD  - Reproductive Medical Center, The First Affiliated Hospital of Zhengzhou 
      University, Zhengzhou, China.
FAU - He, Jingyan
AU  - He J
AD  - Reproductive Medical Center, The First Affiliated Hospital of Zhengzhou 
      University, Zhengzhou, China.
FAU - Zhang, Ruizhe
AU  - Zhang R
AD  - Reproductive Medical Center, The First Affiliated Hospital of Zhengzhou 
      University, Zhengzhou, China.
FAU - Sun, Ying-Pu
AU  - Sun YP
AD  - Reproductive Medical Center, The First Affiliated Hospital of Zhengzhou 
      University, Zhengzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biol Reprod
JT  - Biology of reproduction
JID - 0207224
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (Gonadotropins)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 4TI98Z838E (Estradiol)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Amphiregulin/genetics/*metabolism
MH  - ErbB Receptors/genetics/metabolism
MH  - Estradiol/blood
MH  - Female
MH  - Gene Expression Regulation
MH  - Gonadotropins/administration & dosage/pharmacology
MH  - Granulosa Cells/*metabolism
MH  - Humans
MH  - Oocytes/metabolism
MH  - Ovarian Hyperstimulation Syndrome/*metabolism
MH  - Prospective Studies
MH  - Receptor, ErbB-2/genetics/*metabolism
MH  - Up-Regulation/physiology
MH  - Vascular Endothelial Growth Factor A/genetics/*metabolism
OTO - NOTNLM
OT  - AREG
OT  - EGFR
OT  - OHSS
OT  - VEGF
OT  - granulosa cells
OT  - in vitro fertilization
EDAT- 2019/06/06 06:00
MHDA- 2020/09/30 06:00
CRDT- 2019/06/06 06:00
PHST- 2018/09/07 00:00 [received]
PHST- 2019/03/14 00:00 [revised]
PHST- 2019/05/29 00:00 [accepted]
PHST- 2019/06/06 06:00 [pubmed]
PHST- 2020/09/30 06:00 [medline]
PHST- 2019/06/06 06:00 [entrez]
AID - 5511777 [pii]
AID - 10.1093/biolre/ioz091 [doi]
PST - ppublish
SO  - Biol Reprod. 2019 Aug 1;101(2):426-432. doi: 10.1093/biolre/ioz091.