PMID- 31551156
OWN - NLM
STAT- MEDLINE
DCOM- 20200519
LR  - 20200519
IS  - 1556-5653 (Electronic)
IS  - 0015-0282 (Linking)
VI  - 112
IP  - 5
DP  - 2019 Nov
TI  - Investigating the impact of local inflammation on granulosa cells and follicular 
      development in women with ovarian endometriosis.
PG  - 882-891.e1
LID - S0015-0282(19)30580-1 [pii]
LID - 10.1016/j.fertnstert.2019.07.007 [doi]
AB  - OBJECTIVE: To investigate the possible impact of local inflammation on granulosa 
      cells (GCs) and follicular development in endometriosis patients. DESIGN: 
      Prospective study with related paired design. SETTING: Reproductive medicine 
      center. PATIENT(S): A total of 80 endometriosis patients and 104 controls, with 
      cultured GCs collected from control participants younger than 35 years. 
      INTERVENTION(S): Tumor necrosis factor-alpha (TNF-alpha) and nuclear factor kappaB (NF-kappaB) 
      inhibitor. MAIN OUTCOME MEASURE(S): Intrafollicular concentrations of cytokines 
      measured with ELISA, NF-kappaB binding levels with electrophoretic mobility shift 
      assay (EMSA), and telomerase activity (TA) with quantitative-telomeric repeat 
      amplification protocol (Q-TRAP) assay, and protein and mRNA expression with 
      Western blot and polymerase chain reaction analyses, respectively. RESULT(S): 
      Patients with endometriosis exhibited a statistically significantly lower antral 
      follicle count (11.48 +/- 8.11 vs. 15.68 +/- 8.56), lower number of retrieved oocytes 
      (8.28 +/- 6.69 vs. 10.87 +/- 6.26), and lower number of mature oocytes (6.67 +/- 6.09 
      vs. 8.53 +/- 5.69). The GCs from endometriosis patients showed higher NF-kappaB binding 
      activity and increased expression of inhibitor of NF-kappaB kinase subunit beta (IKKbeta, 
      2.743-fold) and NF-kappaB inhibitor alpha (IkappaBalpha, 5.017-fold). Their NF-kappaB p65 expression 
      was negatively associated with mature oocytes (bNF-kappaB' = -0.304, R(2) = 0.195, R 
      = 0.442) but positively associated with intrafollicular TNF-alpha (r = 0.37); TA 
      showed a negative relationship with NF-kappaB binding levels (r = -0.667). Tumor 
      necrosis factor-alpha induced expression of IkappaBalpha (5.408-fold) and NF-kappaB p65 
      (1.400-fold) but lowered human telomerase reverse transcriptase (hTERT) and TA 
      levels (0.0009 vs. 0.5619) in cultured GCs. However, inhibiting NF-kappaB obviously 
      increased hTERT expression (1.988-fold). CONCLUSION(S): Endometriosis showed 
      activated NF-kappaB pathways in GCs, which might negatively affect TA and oocyte 
      quality. Intrafollicular TNF-alpha might down-regulate TA and hTERT via NF-kappaB 
      pathway, but further studies are required.
CI  - Copyright (c) 2019 American Society for Reproductive Medicine. Published by 
      Elsevier Inc. All rights reserved.
FAU - Li, Ying
AU  - Li Y
AD  - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene 
      Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 
      People's Republic of China; Reproductive Medicine Center, Sun Yat-Sen Memorial 
      Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
FAU - Li, Ruiqi
AU  - Li R
AD  - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene 
      Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 
      People's Republic of China; Reproductive Medicine Center, Sun Yat-Sen Memorial 
      Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
FAU - Ouyang, Nengyong
AU  - Ouyang N
AD  - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene 
      Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 
      People's Republic of China; Reproductive Medicine Center, Sun Yat-Sen Memorial 
      Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
FAU - Dai, Kailing
AU  - Dai K
AD  - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene 
      Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 
      People's Republic of China; Reproductive Medicine Center, Sun Yat-Sen Memorial 
      Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
FAU - Yuan, Ping
AU  - Yuan P
AD  - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene 
      Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 
      People's Republic of China; Reproductive Medicine Center, Sun Yat-Sen Memorial 
      Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
FAU - Zheng, Lingyan
AU  - Zheng L
AD  - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene 
      Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 
      People's Republic of China; Reproductive Medicine Center, Sun Yat-Sen Memorial 
      Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
FAU - Wang, Wenjun
AU  - Wang W
AD  - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene 
      Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 
      People's Republic of China; Reproductive Medicine Center, Sun Yat-Sen Memorial 
      Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China. 
      Electronic address: wenjungzcn@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190921
PL  - United States
TA  - Fertil Steril
JT  - Fertility and sterility
JID - 0372772
RN  - 0 (Inflammation Mediators)
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
CIN - Fertil Steril. 2019 Nov;112(5):813-814. PMID: 31731940
MH  - Adult
MH  - Cells, Cultured
MH  - Endometriosis/*blood/*diagnosis
MH  - Female
MH  - Granulosa Cells/*metabolism
MH  - Humans
MH  - Inflammation/blood/diagnosis
MH  - Inflammation Mediators/*blood
MH  - NF-kappa B/blood
MH  - Ovarian Follicle/*growth & development/*metabolism
MH  - Pregnancy
MH  - Prospective Studies
MH  - Tumor Necrosis Factor-alpha/blood
OTO - NOTNLM
OT  - Endometriosis
OT  - NF-kappa B
OT  - hTERT
OT  - inflammatory cytokines
OT  - telomerase activity
EDAT- 2019/09/26 06:00
MHDA- 2020/05/20 06:00
CRDT- 2019/09/26 06:00
PHST- 2019/03/05 00:00 [received]
PHST- 2019/06/10 00:00 [revised]
PHST- 2019/07/02 00:00 [accepted]
PHST- 2019/09/26 06:00 [pubmed]
PHST- 2020/05/20 06:00 [medline]
PHST- 2019/09/26 06:00 [entrez]
AID - S0015-0282(19)30580-1 [pii]
AID - 10.1016/j.fertnstert.2019.07.007 [doi]
PST - ppublish
SO  - Fertil Steril. 2019 Nov;112(5):882-891.e1. doi: 10.1016/j.fertnstert.2019.07.007. 
      Epub 2019 Sep 21.