DUOX2 is the Main Generator of H₂O₂ in the Ovary.

LH/hCG induction of reactive oxygen species is require for successful ovulation and H₂O₂ was shown to fully mimic the effect of LH/hCG in mice-ovulation. However, the molecular process that generates H₂O₂ in the ovary during ovulation remains largely unknown. DUOX2, is known as H₂O ₂ generator and was shown to be significantly up-regulated in our library of ovulation associated genes.

We hypothesize that DUOX2 is the main generator of H₂O₂ in the ovary and play a critical role in ovulation. Therefore, we aim to characterize DUOX2 expression and regulation in the human ovary and elucidate the functional role of DUOX2 during ovulation.

We show that DUOX2 is more abundant in cumulus cells (CCs) then in mural granulosa cells (MGCs) and in CCs isolated from mature then immature COCs. To confirm the effect of LH/hCG on DUOX2 induction, MGCs in culture were stimulated with hCG for 24h, showing the induction of DUOX2.To examine the role of duox2 in H₂O₂ production, we stimulated MGCs with hCG in the presence or absence of pharmacologic doses of the inhibitor of DUOX2, DPI. The result show that DPI blocked hCG induced H₂O₂ secretion.

Taken-together our in-vivo and in-vitro results, demonstrate that DUOX2 is an LH/hCG target gene and is upregulated during the preovulatory period especially in cumulus cells. Importantly, we show that DUOX2 activity is require for hCG elevation of extracellular H2O2 in granulosa cells, suggesting a possible role for DUOX2 in ovulation.