The role of vasorin in ovarian physiology

Nitzan Rimon

The ovary, the female gonad, is composed of follicles, each of which containing a prophase- arrested oocyte
surrounded by nursing somatic cells (granulosa and thecal cells). Bidirectional communication between the
oocyte and the somatic cells is crucial for the maintenance of meiotic arrest, proper foliculogenesis,
ovulation and the formation of the corpus luteum (CL).

Many of the signaling molecules involved in the dialog between the oocyte and the somatic compartment of the ovarian follicle belong to the transforming growth factor-β (TGFβ). Among other regulatory mechanisms, TGFβ signaling is attenuated by its binding to the soluble form of Vasorin/ATIA (Vasn), a type I membrane protein that was recently shown to be cleaved in the plasma membrane by Adam17. In addition, Vasn was found to be a hypoxia inducible factor (HIF)-1 target, which is expressed in the mitochondria and protects cells against TNFα and hypoxia-induced apoptosis.

The ovarian follicle is scarcely vascularized and hypoxic conditions characterize the ovary and control its proper function. Therefore, in addition to its role in regulating (TGFβ) activity, Vasn may also be involved in protecting ovarian cells from possible hypoxic damage.

Our initial results demonstrate that granulosa cells express Vasn during different developmental stages and that its expression is upregulated by luteinizing hormone (LH). Importantly, Vasn knock out (KO) was shown to cause impaired fertility in males due to increased apoptosis in the testis and to bring about infertility in female. Taking this information into account, we hypothesize that Vasn may have an important role in ovarian physiology. Our present study aims at discovering the function of Vasn in the female reproductive system, with a particular interest at the ovary.