STUDY QUESTION: Do the adipocytokines, leptin and adiponectin affect the 
granulosa cell expression of anti-Mullerian hormone (AMH) and its receptor 
(AMHR-II)?
SUMMARY ANSWER: Leptin suppresses AMH mRNA levels in human luteinized granulosa 
cells through the JAK2/STAT3 pathway, while adiponectin has no such effect.
WHAT IS KNOWN ALREADY: AMH is one of the most reliable markers of ovarian 
reserve. Serum AMH levels decline with obesity. Obesity is associated with 
elevated leptin and reduced adiponectin levels.
STUDY DESIGN, SIZE AND DURATION: This prospective study included 60 infertile 
women undergoing fresh IVF and ICSI cycles utilizing autologous oocytes at 
Montefiore's Institute for Reproductive Medicine and Health between July 2010 
and April 2012.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Follicular fluid was collected from 
small (SFs; <14 mm) and large follicles (LFs; ≥14 mm) from 38 participants. 
Total RNA was extracted separately from mural and cumulus granulosa cells and 
mRNA levels were measured by RT-PCR. In an additional group of participants (N = 
22), primary cumulus and mural granulosa cells (pooled SFs and LFs) were 
cultured in media alone or with addition of either leptin (N = 7), adiponectin 
(N = 8) or JAK2/STAT3 inhibitor + leptin (N = 7), and AMH and AMHR-II mRNA 
levels measured. Levels of AMH, leptin and adiponectin protein were measured in 
follicular fluid.
MAIN RESULTS AND THE ROLE OF CHANCE: AMH and AMHR-II mRNA and follicular fluid 
AMH protein levels were inversely correlated with age. AMH mRNA expression was 
six times higher in cumulus compared with mural granulosa cells in SFs (P< 0.05) 
and eight times higher in cumulus compared with mural granulosa cells in LFs (P 
< 0.001). In follicular fluid, leptin protein level positively correlated (r = 
0.7, P = 0.03), while adiponectin protein level inversely correlated (r = -0.46, 
P = 0.02) with BMI. Leptin treatment suppressed AMH and AMHR-II mRNA in both 
cumulus and mural granulosa cells (all P < 0.05). In the presence of JAK2/STAT3 
inhibitor, leptin treatment did not alter AMH but continued to suppress AMHR-II 
mRNA in cumulus cells (P = 0.02). Adiponectin treatment did not alter AMH or 
AMHR-II mRNA levels.
LIMITATIONS, REASONS FOR CAUTION: This study included a luteinized granulosa 
cell model as these cells were collected from women who were hyperstimulated 
with gonadotrophins. The results obtained may not fully extrapolate to 
non-luteinized granulosa cells.
WIDER IMPLICATIONS OF THE FINDINGS: Leptin may program abnormal AMH signaling, 
thereby resulting in ovarian dysfunction. This study opens a new perspective for 
understanding the low ovarian reserve seen in obese women and provides new 
insights into potential mechanisms that explain the lower AMH seen in obese 
women. Whether our findings explain the worse response to ovulation induction 
observed in obese women needs to be further elucidated.