PMID- 31887337
OWN - NLM
STAT- MEDLINE
DCOM- 20210104
LR  - 20210104
IS  - 1872-8057 (Electronic)
IS  - 0303-7207 (Linking)
VI  - 504
DP  - 2020 Mar 15
TI  - Rapamycin treatment maintains developmental potential of oocytes in mice and 
      follicle reserve in human cortical fragments grafted into immune-deficient mice.
PG  - 110694
LID - S0303-7207(19)30396-X [pii]
LID - 10.1016/j.mce.2019.110694 [doi]
AB  - The ovarian follicle pool size is limited; it decreases with age and following 
      germ cell-damaging chemo- or radiation therapies. Due to a trend of delaying 
      child-bearing age in the modern society, it is important to investigate the 
      possibility to maintain the follicle reserve for middle-aged women and 
      cancer-bearing patients subject to therapies. Earlier studies demonstrated the 
      important role of the mammalian targets of the rapamycin (MTOR) signaling pathway 
      in the activation of primordial follicles and suggested that treatment with the 
      MTOR inhibitor rapamycin could maintain the follicle pool in rodents. Here, we 
      confirmed the ability of rapamycin treatment for 3 weeks to suppress primordial 
      follicle development and to maintain follicle pool size in mice. We further 
      demonstrated that the developmental potential of oocytes was not affected by 
      rapamycin treatment and the effect of rapamycin to decrease initial follicle 
      recruitment is reversible. Using human ovarian cortical fragments grafted into 
      immune-deficient mice, we demonstrated the ability of rapamycin to suppress 
      follicle growth from the primordial stage. Our studies provide the basis for 
      further studies on the possibility of using MTOR inhibitors to maintain follicle 
      reserve in middle-aged women and cancer patients before/during germ cell-damaging 
      therapies.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Yorino Sato
AU  - Yorino Sato
AD  - Department of Obstetrics and Gynecology, St. Marianna University School of 
      Medicine, Kawasaki, Kanagawa, 216-8511, Japan.
FAU - Kawamura, Kazuhiro
AU  - Kawamura K
AD  - Department of Obstetrics and Gynecology, St. Marianna University School of 
      Medicine, Kawasaki, Kanagawa, 216-8511, Japan. Electronic address: 
      kazuhironanami@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191227
PL  - Ireland
TA  - Mol Cell Endocrinol
JT  - Molecular and cellular endocrinology
JID - 7500844
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Aging/physiology
MH  - Animals
MH  - Female
MH  - Germ Cells/drug effects/metabolism/transplantation
MH  - Heterografts
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Mice, SCID
MH  - Middle Aged
MH  - Oocytes/*drug effects/physiology
MH  - Oogenesis/*drug effects/physiology
MH  - Ovarian Follicle/*drug effects/physiology
MH  - Ovarian Reserve/*drug effects
MH  - Ovary/drug effects/metabolism/*transplantation
MH  - Pregnancy
MH  - Sirolimus/*pharmacology
OTO - NOTNLM
OT  - MTOR
OT  - Oocyte developmental potential
OT  - Ovarian reserve
OT  - Primordial follicle
OT  - Rapamycin
EDAT- 2019/12/31 06:00
MHDA- 2021/01/05 06:00
CRDT- 2019/12/31 06:00
PHST- 2019/08/13 00:00 [received]
PHST- 2019/12/23 00:00 [revised]
PHST- 2019/12/24 00:00 [accepted]
PHST- 2019/12/31 06:00 [pubmed]
PHST- 2021/01/05 06:00 [medline]
PHST- 2019/12/31 06:00 [entrez]
AID - S0303-7207(19)30396-X [pii]
AID - 10.1016/j.mce.2019.110694 [doi]
PST - ppublish
SO  - Mol Cell Endocrinol. 2020 Mar 15;504:110694. doi: 10.1016/j.mce.2019.110694. Epub 
      2019 Dec 27.