Alteration of cytokine production in follicular cystic ovaries induced in mice by neonatal estradiol injection

PROBLEM: Neonatal estradiol injections in mice lead to follicular cystic ov aries that are similar to ovaries in patients with polycystic ovarian syndr ome (PCOS). The present study examined ovarian cytokine production followin g neonatal estradiol injection. METHOD OF STUDY: Female (C3H/HeJ x 129/HeJ)F-1 mice were injected daily wit h 20 mu g 17 beta-estradiol from 0-3 days postpartum. At intervals, animals were sacrificed to determine ovarian architecture, circulating levels of e stradiol, ovarian and peritoneal machrophage cytokine production, and ovari an P450 aromatase enzyme mRNA levels. RESULTS: Similar to PCOS, our results show that neonatally estradiol-inject ed mice have lower levels of circulating estrogen that are correlated with decreased mRNA levels of P450 aromatase enzyme. Our data also show that fol licular cystic ovaries have increased tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 production. This increase in TNF-alpha and IL-6 product ion is also observed in peritoneal macrophages of estradiol-injected mice. CONCLUSION: The present study showed that neonatal estrogen injection in mi ce has an overall systemic effect on cytokine production. We speculate that increased cytokine production may alter certain important steps in follicu lar maturation, ultimately contributing to ovarian dysfunction.