Association of serum and follicular fluid leptin concentrations with granulosa cell phosphorylated signal transducer and activator of transcription 3 expression in fertile patients with polycystic ovarian syndrome.
OBJECTIVE
Our objective was to evaluate whether polycystic ovarian syndrome (PCOS)-associated infertility is related to alterations of leptin, leptin receptor (Ob-R), and the phosphorylated signal transducer and activator of transcription 3 (p-STAT3)/suppressor of cytokine signal 3 (SOCS3) system in the ovary.


METHODS
A case-control study was conducted in a university hospital.


METHODS
Thirty-one infertile PCOS women with oligoovulation plus polycystic ovarian morphology and 79 infertile women with tubal blockage (control) participated in the study. The subjects were stratified according to in vitro fertilization outcomes: successful and failed subgroups.


METHODS
Serum and follicular fluid (FF) leptin levels were measured with ELISA. RT-PCR and Western blotting were performed to assess expression of mRNA encoding leptin and Ob-R and proteins of p-STAT3 and SOCS3 in granulosa cells (GCs).


RESULTS
Leptin levels in serum and FF of PCOS women were significantly higher than those of control (P < 0.01). There were no significant differences in expression of leptin mRNA and short and long Ob-Rs between PCOS and control (P > 0.05). The p-STAT3 level was decreased in PCOS compared with control (P < 0.01), whereas SOCS3 remained significantly unchanged (P > 0.05). Further analysis showed that serum and FF leptin levels were significantly higher, whereas p-STAT3 in GCs was lower in the failed subgroup of PCOS than those in the successful subgroup of PCOS (P < 0.05).


CONCLUSIONS
Hyperleptinemia and high FF leptin are important pathologies of PCOS with infertility. Lower levels of p-STAT3 in GCs may be related to ovarian leptin resistance and fecundity in PCOS women. Relatively high serum and FF leptin and low p-STAT3 in GCs may account for decreased fertilization, implantation, and pregnancy rates of in vitro fertilization in PCOS women.
Li
Mei-Gen
MG
Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, 2 Xue Shi Road, Hangzhou, Zhejiang, 31006, China.
Ding
Guo-Lian
GL
Chen
Xi-Jing
XJ
Lu
Xi-Ping
XP
Dong
Li-Jun
LJ
Dong
Min-Yue
MY
Yang
Xiao-Fu
XF
Lu
Xiu-E
XE
Huang
He-Feng
HF
D000199:Actins / Q000378:metabolism; D000328:Adult; D015153:Blotting, Western; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005298:Fertility / Q000502:physiology*; D005307:Fertilization in Vitro; D015571:Follicular Fluid / Q000378:metabolism*; D006107:Granulosa Cells / Q000378:metabolism; D006801:Humans; D007247:Infertility, Female / Q000378:metabolism; D020738:Leptin / Q000097:blood / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis* / Q000235:genetics*
D000199:Actins; D020738:Leptin; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins