PMID- 33947426
OWN - NLM
STAT- MEDLINE
DCOM- 20211119
LR  - 20211119
IS  - 1757-2215 (Electronic)
IS  - 1757-2215 (Linking)
VI  - 14
IP  - 1
DP  - 2021 May 4
TI  - Short-term rapamycin administration elevated testosterone levels and exacerbated 
      reproductive disorder in dehydroepiandrosterone-induced polycystic ovary syndrome 
      mice.
PG  - 64
LID - 10.1186/s13048-021-00813-0 [doi]
LID - 64
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a multifactorial endocrinopathy 
      that affects reproduction and metabolism. Mammalian target of rapamycin (mTOR) 
      has been shown to participate in female reproduction under physiological and 
      pathological conditions. This study aimed to investigate the role of mTOR complex 
      1 (mTORC1) signaling in dehydroepiandrosterone (DHEA)-induced PCOS mice. RESULTS: 
      Female C57BL/6J mice were randomly assigned into three groups: control group, 
      DHEA group, and DHEA + rapamycin group. All DHEA-treated mice were administered 
      6 mg/100 g DHEA for 21 consecutive days, and the DHEA + rapamycin group was 
      intraperitoneally injected with 4 mg/kg rapamycin every other day for the last 14 
      days of the DHEA treatment. There was no obvious change in the expression of 
      mTORC1 signaling in the ovaries of the control and DHEA groups. Rapamycin did not 
      protect against DHEA-induced acyclicity and PCO morphology, but impeded follicle 
      development and elevated serum testosterone levels in DHEA-induced mice, which 
      was related with suppressed Hsd3b1, Cyp17a1, and Cyp19a1 expression. Moreover, 
      rapamycin also exacerbated insulin resistance but relieved lipid metabolic 
      disturbance in the short term. CONCLUSIONS: Rapamycin exacerbated reproductive 
      imbalance in DHEA-induced PCOS mice, which characterized by elevated testosterone 
      levels and suppressed steroid synthesis. This underscores the need for new 
      mTORC1-specific and tissue-specific mTOR-related drugs for reproductive 
      disorders.
FAU - Guo, Zaixin
AU  - Guo Z
AD  - Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, 
      Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 
      China.
FAU - Chen, Xiaohan
AU  - Chen X
AD  - Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, 
      Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 
      China.
FAU - Feng, Penghui
AU  - Feng P
AD  - Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, 
      Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 
      China.
FAU - Yu, Qi
AU  - Yu Q
AUID- ORCID: 0000-0001-9737-5957
AD  - Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, 
      Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 
      China. yuqi2008001@sina.com.
LA  - eng
GR  - 2018YFC1002105/National Key Research and Development Program/
GR  - 2017-I2m-2-002/the CAMS Innovation Fund for Medical Sciences (CIFMS)/
PT  - Journal Article
DEP - 20210504
PL  - England
TA  - J Ovarian Res
JT  - Journal of ovarian research
JID - 101474849
RN  - 3XMK78S47O (Testosterone)
RN  - 459AG36T1B (Dehydroepiandrosterone)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Dehydroepiandrosterone/*adverse effects
MH  - Disease Models, Animal
MH  - Female
MH  - Humans
MH  - Mice
MH  - Polycystic Ovary Syndrome/*chemically induced/*drug therapy
MH  - Reproduction/*drug effects
MH  - Sirolimus/*adverse effects
MH  - Testosterone/*adverse effects
PMC - PMC8097915
OTO - NOTNLM
OT  - Hyperandrogenism
OT  - Polycystic ovary syndrome
OT  - Rapamycin
OT  - Steroidogenesis
OT  - mTOR
COIS- The authors declare that they have no competing interests.
EDAT- 2021/05/06 06:00
MHDA- 2021/11/20 06:00
PMCR- 2021/05/04
CRDT- 2021/05/05 05:43
PHST- 2021/01/25 00:00 [received]
PHST- 2021/04/16 00:00 [accepted]
PHST- 2021/05/05 05:43 [entrez]
PHST- 2021/05/06 06:00 [pubmed]
PHST- 2021/11/20 06:00 [medline]
PHST- 2021/05/04 00:00 [pmc-release]
AID - 10.1186/s13048-021-00813-0 [pii]
AID - 813 [pii]
AID - 10.1186/s13048-021-00813-0 [doi]
PST - epublish
SO  - J Ovarian Res. 2021 May 4;14(1):64. doi: 10.1186/s13048-021-00813-0.