Adiponectin (ADIPO) inhibits in vitro growth of murine ovarian follicles

Adiponectin (Adipo) is an adipocyte-derived insulin-sensitizing hormone that regulates glucose and fatty acid metabolism, energy expenditure, and reproduction. Objectives were to investigate expression and function of Adipo and its receptors (AdipoR1 and AdipoR2) in granulosa cells (GC) and oocytes during folliculogenesis and oocyte meiosis. Laboratory study. Meiotically incompetent/competent germinal vesicle-intact (GVI) oocytes and GC from pre-antral/antral follicles were collected from 11/21 day old CF1 mice, respectively. GVI, germinal vesicle break-down, and metaphase II (MII) oocytes were collected following 0, 2, and 16 hours of culture. Sample mRNA was quantified by qPCR. Secondary follicles were isolated and cultured with or without 5μg/ml Adipo. Data were analyzed by Student's t-test. Adipo mRNA was 52 fold higher in meiotically competent than incompetent GVI oocytes (P<0.05), but did not change during meiosis. Both AdipoR1 (1.4 fold P<0.05) and AdipoR2 (2.5 fold P<0.05) transcripts were elevated in MII versus GVI oocytes. GC from antral follicles had more AdipoR1 (1 .9 fold P<0.05) and AdipoR2 (3.5 fold P<0.01) transcripts than GC from pre-antral follicles. Adipo mRNA was 2.5 fold lower in GC from antral follicles than from pre-antral follicles (P<0.05). Meiotic progression of oocytes was not altered by Adipo treatment. Average follicle size at beginning of culture were similar, yet following exposure to Adipo (n=81) follicles were significantly smaller than those not exposed to Adipo (n=73) at day 4 (239±7 vs. 220±6, P<0.05), day 6 (315±9 vs. 286±9, P<0.05) and day 8 (386±12 vs. 352±12, P<0.05) of culture. Adipo and its receptors were expressed in oocytes and GC at all stages examined. Addition of Adipo has no effect on in vitro oocyte meiotic maturation but decreased growth during follicular culture. Studies are now examining effects of fatty acids (Adipo direct metabolic targets) on follicular growth and steroidogenesis.