PMID- 30184105
OWN - NLM
STAT- MEDLINE
DCOM- 20200526
LR  - 20210816
IS  - 1529-7268 (Electronic)
IS  - 0006-3363 (Linking)
VI  - 100
IP  - 3
DP  - 2019 Mar 1
TI  - Effects of letrozole and clomiphene citrate on Wnt signaling pathway in 
      endometrium of polycystic ovarian syndrome and healthy womendagger.
PG  - 641-648
LID - 10.1093/biolre/ioy187 [doi]
AB  - Polycystic ovary syndrome (PCOS) is an endocrine disorder in women of 
      reproductive age. In addition to anovulation, endometrial dysfunction can reduce 
      fertility in PCOS. The cyclical changes of endometrium are controlled by estrogen 
      and progesterone via modulating the Wnt/B-catenin pathway. Clomiphene citrate 
      (CC) and letrozole are used to induce ovulation; unlike letrozole, there is a 
      discrepancy between ovulation and pregnancy rates in CC-treated cycles. Because 
      of the anti-estrogenic effects of CC on endometrium, we compared the expression 
      of the key molecules of the Wnt/B-catenin pathway in the endometrium of women 
      taking CC and letrozole. This study included PCOS and healthy women divided into 
      the groups stimulated with letrozole (5 mg) or CC (100 mg) as well as 
      NO-treatment groups. The endometrial thickness and hormonal profile were measured 
      on day 12 of the menses. Using real-time polymerase chain reaction and western 
      blot, we evaluated mRNA and protein expression of B-catenin, glycogen synthase 
      kinase 3 beta (GSK3B), dickkopf Wnt signaling pathway inhibitor 1 (DKK1), and 
      estrogen receptor 1 (ESR1) in the endometrial samples. Significantly, the mean 
      serum estrogen and progesterone were lower and higher, respectively, in letrozole 
      than CC groups. The endometrial thickness was significantly reduced in CC. The 
      proteins expression of active B-catenin, inactive GSK3B, and ESR1 were 
      significantly decreased in CC-treated groups. The mRNA and protein assessment of 
      DKK1 showed significantly higher expression in CC. Our results indicate that 
      letrozole can provide an acceptable activation of the Wnt/B-catenin pathway, 
      resulting in adequate proliferation of endometrium in the women receiving 
      letrozole compared to CC.
CI  - (c) The Author(s) 2018. Published by Oxford University Press on behalf of Society 
      for the Study of Reproduction.
FAU - Mehdinejadiani, Shayesteh
AU  - Mehdinejadiani S
AD  - Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, 
      Tehran, Iran.
AD  - Cellular and Molecular Research Center, Iran University of Medical Sciences, 
      Tehran, Iran.
FAU - Amidi, Fardin
AU  - Amidi F
AD  - Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, 
      Tehran, Iran.
AD  - Department of Endocrinology and Infertility, Shariati Hospital, Tehran University 
      of Medical Sciences, Tehran, Iran.
FAU - Mehdizadeh, Mehdi
AU  - Mehdizadeh M
AD  - Cellular and Molecular Research Center, Faculty of Advanced Technologies in 
      Medicine, Department of Anatomy, Iran University of Medical Sciences, Tehran, 
      Iran.
FAU - Barati, Mahmood
AU  - Barati M
AD  - Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University 
      of Medical Sciences, Tehran, Iran.
FAU - Pazhohan, Azar
AU  - Pazhohan A
AD  - Department of Midwifery, Urmia Branch, Islamic Azad University, Urmia, Iran.
AD  - Infertility center of Academic Center for Education, Culture and Research, East 
      Azarbaijan, Tabriz, Iran.
FAU - Alyasin, Ashraf
AU  - Alyasin A
AD  - Department of Endocrinology and Infertility, Shariati Hospital, Tehran University 
      of Medical Sciences, Tehran, Iran.
FAU - Mehdinejadiani, Kobra
AU  - Mehdinejadiani K
AD  - Department of Immunology, School of Medicine, Shahid Beheshti University of 
      Medical Sciences, Tehran, Iran.
FAU - Sobhani, Aligholi
AU  - Sobhani A
AD  - Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, 
      Tehran, Iran.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biol Reprod
JT  - Biology of reproduction
JID - 0207224
RN  - 0 (Aromatase Inhibitors)
RN  - 0 (DKK1 protein, human)
RN  - 0 (ESR1 protein, human)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Fertility Agents, Female)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Wnt Proteins)
RN  - 0 (beta Catenin)
RN  - 1HRS458QU2 (Clomiphene)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - 4TI98Z838E (Estradiol)
RN  - 7LKK855W8I (Letrozole)
RN  - 9002-67-9 (Luteinizing Hormone)
RN  - 9002-68-0 (Follicle Stimulating Hormone)
RN  - EC 2.7.11.1 (GSK3B protein, human)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
SB  - IM
MH  - Adult
MH  - Aromatase Inhibitors/pharmacology
MH  - Clomiphene/*pharmacology
MH  - Endometrium/*drug effects/metabolism
MH  - Estradiol/metabolism
MH  - Estrogen Receptor alpha/genetics/metabolism
MH  - Female
MH  - Fertility Agents, Female/pharmacology
MH  - Follicle Stimulating Hormone/metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Glycogen Synthase Kinase 3 beta/genetics/metabolism
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/genetics/metabolism
MH  - Letrozole/*pharmacology
MH  - Luteinizing Hormone/metabolism
MH  - Polycystic Ovary Syndrome/*metabolism
MH  - Progesterone/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Wnt Proteins/genetics/*metabolism
MH  - beta Catenin/genetics/metabolism
OTO - NOTNLM
OT  - Wnt signaling pathway
OT  - clomiphene citrate
OT  - endometrium
OT  - letrozole
OT  - polycystic ovary syndrome
EDAT- 2018/09/06 06:00
MHDA- 2020/05/27 06:00
CRDT- 2018/09/06 06:00
PHST- 2018/02/25 00:00 [received]
PHST- 2018/07/11 00:00 [revised]
PHST- 2018/09/06 06:00 [pubmed]
PHST- 2020/05/27 06:00 [medline]
PHST- 2018/09/06 06:00 [entrez]
AID - 5089964 [pii]
AID - 10.1093/biolre/ioy187 [doi]
PST - ppublish
SO  - Biol Reprod. 2019 Mar 1;100(3):641-648. doi: 10.1093/biolre/ioy187.