PMID- 35436937
OWN - NLM
STAT- MEDLINE
DCOM- 20220420
LR  - 20220716
IS  - 1477-7827 (Electronic)
IS  - 1477-7827 (Linking)
VI  - 20
IP  - 1
DP  - 2022 Apr 18
TI  - Rapamycin improves the quality and developmental competence of mice oocytes by 
      promoting DNA damage repair during in vitro maturation.
PG  - 67
LID - 10.1186/s12958-022-00943-0 [doi]
LID - 67
AB  - BACKGROUND: Increasing evidence has shown that the mammalian target of rapamycin 
      (mTOR) pathway plays a critical role in oocyte meiosis and embryonic development, 
      however, previous studies reporting the effects of rapamycin on oocyte IVM showed 
      different or even opposite results, and the specific mechanisms were not clear. 
      METHODS: The immature oocytes from female mice underwent IVM with rapamycin at 
      different concentrations to select an optimal dose. The maturation rate, 
      activation rate, subsequent cleavage and blastocyst formation rates, spindle 
      assembly, chromosome alignment, mitochondrial membrane potential (MMP), ROS 
      levels, and DNA damage levels were evaluated and compared in oocytes matured with 
      or without rapamycin. In addition, the expression levels of genes associated with 
      mTORC1 pathway, spindle assembly, antioxidant function, and DNA damage repair 
      (DDR) were also assessed and compared. RESULTS: Rapamycin at 10 nM was selected 
      as an optimal concentration based on the higher maturation and activation rate of 
      IVM oocytes. Following subsequent culture, cleavage and blastocyst formation 
      rates were elevated in activated embryos from the rapamycin group. Additionally, 
      oocytes cultured with 10 nM rapamycin presented decreased ROS levels, reduced 
      chromosome aberration, and attenuated levels of gamma-H2AX. No significant effects on 
      the percentages of abnormal spindle were observed. Correspondingly, the 
      expressions of Nrf2, Atm, Atr, and Prkdc in IVM oocytes were markedly increased, 
      following the inhibition of mTORC1 pathway by 10 nM rapamycin. CONCLUSION: 
      Rapamycin at 10 nM could ameliorate the developmental competence and quality of 
      IVM oocytes of mice, mainly by improving the chromosome alignments. The 
      inhibition of mTORC1 pathway, which involved in activating DDR-associated genes 
      may act as a potential mechanism for oocyte quality improvement by rapamycin.
CI  - (c) 2022. The Author(s).
FAU - Yang, Qiyu
AU  - Yang Q
AD  - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, No.1095, Jiefang Road, Wuhan, 430030, 
      China.
FAU - Xi, Qingsong
AU  - Xi Q
AD  - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, No.1095, Jiefang Road, Wuhan, 430030, 
      China.
FAU - Wang, Meng
AU  - Wang M
AD  - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, No.1095, Jiefang Road, Wuhan, 430030, 
      China.
FAU - Long, Rui
AU  - Long R
AD  - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, No.1095, Jiefang Road, Wuhan, 430030, 
      China.
FAU - Hu, Juan
AU  - Hu J
AD  - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, No.1095, Jiefang Road, Wuhan, 430030, 
      China.
FAU - Li, Zhou
AU  - Li Z
AD  - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, No.1095, Jiefang Road, Wuhan, 430030, 
      China.
FAU - Ren, Xinling
AU  - Ren X
AD  - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, No.1095, Jiefang Road, Wuhan, 430030, 
      China.
FAU - Zhu, Lixia
AU  - Zhu L
AD  - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, No.1095, Jiefang Road, Wuhan, 430030, 
      China. zhulixia027@163.com.
FAU - Jin, Lei
AU  - Jin L
AD  - Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, No.1095, Jiefang Road, Wuhan, 430030, 
      China. leijintongjih@qq.com.
LA  - eng
PT  - Journal Article
DEP - 20220418
PL  - England
TA  - Reprod Biol Endocrinol
JT  - Reproductive biology and endocrinology : RB&E
JID - 101153627
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Blastocyst/physiology
MH  - *DNA Damage
MH  - Embryonic Development/genetics
MH  - Female
MH  - *In Vitro Oocyte Maturation Techniques/methods
MH  - Mammals
MH  - Mechanistic Target of Rapamycin Complex 1/genetics/metabolism
MH  - Mice
MH  - Oocytes/metabolism
MH  - Pregnancy
MH  - Reactive Oxygen Species/metabolism
MH  - *Sirolimus/pharmacology
PMC - PMC9014618
OTO - NOTNLM
OT  - DNA damage
OT  - In vitro maturation
OT  - Oocyte quality
OT  - Rapamycin
OT  - mTOR
COIS- The authors declare that they have no competing interests.
EDAT- 2022/04/20 06:00
MHDA- 2022/04/21 06:00
PMCR- 2022/04/18
CRDT- 2022/04/19 05:09
PHST- 2021/12/09 00:00 [received]
PHST- 2022/04/09 00:00 [accepted]
PHST- 2022/04/19 05:09 [entrez]
PHST- 2022/04/20 06:00 [pubmed]
PHST- 2022/04/21 06:00 [medline]
PHST- 2022/04/18 00:00 [pmc-release]
AID - 10.1186/s12958-022-00943-0 [pii]
AID - 943 [pii]
AID - 10.1186/s12958-022-00943-0 [doi]
PST - epublish
SO  - Reprod Biol Endocrinol. 2022 Apr 18;20(1):67. doi: 10.1186/s12958-022-00943-0.