PMID- 30145913
OWN - NLM
STAT- MEDLINE
DCOM- 20190611
LR  - 20211204
IS  - 1473-0766 (Electronic)
IS  - 0951-3590 (Linking)
VI  - 35
IP  - 1
DP  - 2019 Jan
TI  - Follicle loss and PTEN/PI3K/mTOR signaling pathway activated in LepR-mutated 
      mice.
PG  - 44-48
LID - 10.1080/09513590.2018.1490714 [doi]
AB  - Female mice (Y123F) with substitution mutations introduced through homologous 
      gene targeting, replacing the three tyrosine residues of LepR, Tyr985, Tyr1077, 
      and Tyr1138 with phenylalanine, could induce infertility. This study aimed to 
      describe the reproductive alteration and to explore its mechanism. We compared 
      the reproductive characteristics in the female homozygous (HOM) Y123F mice and 
      wild-type (WT) littermates, analyzing the expression of downstream molecules of 
      LepR, like protein kinase B (Akt)/mammalian target of rapamycin (mTOR), 
      phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and insulin 
      receptor substrate (IRS) in the ovaries. The results showed that 10-week old 
      female Y123F HOM exhibited no reproductive periods, declined anti-mullerian 
      hormone (AMH) levels in the serum and ovaries, reduced primordial follicles, 
      primary follicles, secondary follicles, antral follicles and hardly no corpus 
      lutea (all p < .05). The phosphorylation of downsream Akt, mTOR, S6K1 and eIF4B 
      of LepR were all elevated in the ovaries of the mutated female mice. They also 
      presented a decreased phosphorylation of IRS-1, IRS-2, and PTEN, and a 
      strengthened phosphorylation of FOXO-3A in the ovaries. In conclusions, LepR 
      mutation could result in follicle loss and activation of PTEN/PI3K/Akt/mTOR 
      pathway in adult female mice, independent of insulin signaling pathway.
FAU - Xia, Hexia
AU  - Xia H
AD  - a Department of Reproductive Endocrinology, Obstetrics and Gynecology Hospital , 
      Fudan University , Shanghai , People's Republic of China.
AD  - b Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases , 
      Shanghai , People's Republic of China.
FAU - Zhang, Ruixiu
AU  - Zhang R
AD  - a Department of Reproductive Endocrinology, Obstetrics and Gynecology Hospital , 
      Fudan University , Shanghai , People's Republic of China.
AD  - b Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases , 
      Shanghai , People's Republic of China.
FAU - Guan, Haiyun
AU  - Guan H
AD  - a Department of Reproductive Endocrinology, Obstetrics and Gynecology Hospital , 
      Fudan University , Shanghai , People's Republic of China.
AD  - b Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases , 
      Shanghai , People's Republic of China.
FAU - Zhang, Wei
AU  - Zhang W
AD  - a Department of Reproductive Endocrinology, Obstetrics and Gynecology Hospital , 
      Fudan University , Shanghai , People's Republic of China.
AD  - b Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases , 
      Shanghai , People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20180826
PL  - England
TA  - Gynecol Endocrinol
JT  - Gynecological endocrinology : the official journal of the International Society 
      of Gynecological Endocrinology
JID - 8807913
RN  - 0 (Insulin)
RN  - 0 (Receptors, Leptin)
RN  - 80497-65-0 (Anti-Mullerian Hormone)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
SB  - IM
MH  - Animals
MH  - Anti-Mullerian Hormone/metabolism
MH  - Female
MH  - Infertility, Female/genetics/*metabolism
MH  - Insulin/metabolism
MH  - Mice
MH  - Oocytes/metabolism
MH  - Ovarian Follicle/*metabolism
MH  - PTEN Phosphohydrolase/*metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphorylation
MH  - Receptors, Leptin/*genetics/metabolism
MH  - Signal Transduction/*physiology
MH  - TOR Serine-Threonine Kinases/*metabolism
OTO - NOTNLM
OT  - AMH
OT  - Leptin receptor
OT  - PTEN
OT  - mTOR
OT  - primordial follicle
EDAT- 2018/08/28 06:00
MHDA- 2019/06/14 06:00
CRDT- 2018/08/28 06:00
PHST- 2018/08/28 06:00 [pubmed]
PHST- 2019/06/14 06:00 [medline]
PHST- 2018/08/28 06:00 [entrez]
AID - 10.1080/09513590.2018.1490714 [doi]
PST - ppublish
SO  - Gynecol Endocrinol. 2019 Jan;35(1):44-48. doi: 10.1080/09513590.2018.1490714. 
      Epub 2018 Aug 26.