PMID- 37672216
OWN - NLM
STAT- MEDLINE
DCOM- 20231218
LR  - 20240103
IS  - 1529-7268 (Electronic)
IS  - 0006-3363 (Linking)
VI  - 109
IP  - 6
DP  - 2023 Dec 11
TI  - Melatonin-pretreated human umbilical cord mesenchymal stem cells improved 
      endometrium regeneration and fertility recovery through macrophage 
      immunomodulation in rats with intrauterine adhesionsdagger.
PG  - 918-937
LID - 10.1093/biolre/ioad102 [doi]
AB  - Intrauterine adhesions (IUA) are a common gynecological problem. Stem cell 
      therapy has been widely used in the treatment of IUA. However, due to the complex 
      and harsh microenvironment of the uterine cavity, the effectiveness of such 
      therapy is greatly inhibited. This study aimed to investigate whether melatonin 
      pretreatment enhances the efficacy of human umbilical cord mesenchymal stem cells 
      (HucMSCs) in IUA treatment in rats. First, we explored the effect of melatonin on 
      the biological activity of HucMSCs in vitro through a macrophage co-culture 
      system, Cell Counting Kit 8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU), flow 
      cytometry, immunofluorescence staining, and qRT-PCR. Subsequently, we established 
      the IUA rat model and tracked the distribution of HucMSCs in this model. In 
      addition, we observed the number of M1 and M2 macrophages through 
      immunofluorescence staining and detected the levels of inflammatory cytokines. 
      Four weeks after cell transplantation, HE, Masson, and immunohistochemical 
      staining were performed. In vitro experiments showed that melatonin pretreatment 
      of HucMSCs promoted proliferation, reduced apoptosis, up-regulated the stemness 
      gene, and regulated macrophage polarization. In vivo, melatonin pretreatment 
      caused more HucMSCs to remain in the uterine cavity. Melatonin-pretreated HucMSCs 
      recruited more macrophages, regulated macrophage polarization, and reduced 
      inflammation. Melatonin-pretreated HucMSCs relieved fibrosis, increased 
      endometrium thickness, and up-regulated CD34, vimentin, proliferating cell 
      nuclear antigen (PCNA), and alpha small muscle antigen (alpha-SMA) expression. 
      Fertility tests showed that melatonin-pretreated HucMSCs increased the number of 
      embryos. In summary, pretreatment with melatonin was beneficial for HucMSC 
      treatment because it enhanced the cell's ability to recruit macrophages and 
      regulate macrophage polarization, which led to the regeneration of the 
      endometrium and improved pregnancy outcomes.
CI  - (c) The Author(s) 2023. Published by Oxford University Press on behalf of Society 
      for the Study of Reproduction. All rights reserved. For permissions, please 
      e-mail: journals.permissions@oup.com.
FAU - Qin, Weili
AU  - Qin W
AD  - Center of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical 
      University, Nanning, China.
FAU - Wang, Jiawei
AU  - Wang J
AD  - Center of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical 
      University, Nanning, China.
AD  - Reproductive and Genetic Hospital, The First Affiliated Hospital of University of 
      Science and Technology of China (USTC), Division of Life Sciences and Medicine, 
      University of Science and Technology of China, Hefei, China.
FAU - Hu, Qianwen
AU  - Hu Q
AD  - Center of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical 
      University, Nanning, China.
FAU - Qin, Rongyan
AU  - Qin R
AD  - Center of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical 
      University, Nanning, China.
FAU - Ma, Nana
AU  - Ma N
AD  - Center of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical 
      University, Nanning, China.
FAU - Zheng, Fengque
AU  - Zheng F
AD  - Center of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical 
      University, Nanning, China.
FAU - Tian, Wencai
AU  - Tian W
AD  - Center of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical 
      University, Nanning, China.
FAU - Jiang, Jinghang
AU  - Jiang J
AD  - Center of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical 
      University, Nanning, China.
FAU - Li, Ting
AU  - Li T
AD  - Center of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical 
      University, Nanning, China.
FAU - Jin, Yufu
AU  - Jin Y
AD  - Center of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical 
      University, Nanning, China.
FAU - Liao, Ming
AU  - Liao M
AD  - Center of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical 
      University, Nanning, China.
FAU - Qin, Aiping
AU  - Qin A
AD  - Center of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical 
      University, Nanning, China.
LA  - eng
GR  - 81960280/National Natural Science Foundation of China/
GR  - 2018GXNSFAA050136/Natural Science Foundation of Guangxi Zhuang Autonomous Region/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biol Reprod
JT  - Biology of reproduction
JID - 0207224
RN  - JL5DK93RCL (Melatonin)
SB  - IM
MH  - Pregnancy
MH  - Female
MH  - Rats
MH  - Humans
MH  - Animals
MH  - *Melatonin/pharmacology/metabolism
MH  - Endometrium/metabolism
MH  - *Uterine Diseases/therapy/metabolism
MH  - *Mesenchymal Stem Cells
MH  - Fertility
MH  - Macrophages
MH  - Umbilical Cord
OTO - NOTNLM
OT  - endometrial regeneration
OT  - intrauterine adhesions
OT  - macrophage immunomodulation
OT  - melatonin pretreated
OT  - stem cell therapy
EDAT- 2023/09/06 12:42
MHDA- 2023/12/18 06:42
CRDT- 2023/09/06 11:23
PHST- 2023/02/10 00:00 [received]
PHST- 2023/06/22 00:00 [revised]
PHST- 2023/08/22 00:00 [accepted]
PHST- 2023/12/18 06:42 [medline]
PHST- 2023/09/06 12:42 [pubmed]
PHST- 2023/09/06 11:23 [entrez]
AID - 7261559 [pii]
AID - 10.1093/biolre/ioad102 [doi]
PST - ppublish
SO  - Biol Reprod. 2023 Dec 11;109(6):918-937. doi: 10.1093/biolre/ioad102.