Reproductive success is dependent on ovulation of a developmentally competent oocyte. However, the molecular mechanisms underlying ovulation are ill-defined. Following the ovulatory luteinising hormone (LH)-surge, cumulus cells become transiently migratory and invasive, predicted to be required for ovulation. What regulates this migratory phenotype is not clear. Interestingly, Sema7a, known to alter the migratory phenotype in other cells, is dysregulated in granulosa cells (GCs) of the anovulatory progesterone receptor null mouse (PRKO; microarray data). We hypothesised that SEMA7a abundance in the periovulatory follicle plays a role in regulating the migratory phenotype of the cumulus oocyte complex (COC) during ovulation. We confirmed that Sema7a was 2.3-fold higher in GCs from infertile PRKO mice than GCs from fertile heterozygous littermates at 8 h post-hCG (P<0.05). During the ovulatory period Sema7a was significantly reduced by 13- and 6.8-fold at 4 h post hCG-administration in COCs and GCs, respectively. In both cell types Sema7a increased following ovulation (16 h post-hCG). In antral follicles SEMA7A protein was predominantly localised to the granulosa cells on the apical side. This specific pattern was lost following post hCG. Localisation of SEMA7a in a particular spatiotemporal pattern prior to hCG may be due to interacting effects of hypoxia and FSH. We found both hypoxia (2%O2) and FSH significantly increased Sema7a during in vitro culture of GCs (P<0.05). SEMA7A receptors Plexin C1 and β1 integrins are known to decrease and increase migration, respectively. Plxnc1 was significantly downregulated in both the COC and GCs post-hCG while Itgb1 remained constant prior to ovulation and significantly upregulated following ovulation in both cell types. Interestingly expression of Itga5 whose gene product forms a heterodimer with β1 integrin and promotes migration following SEMA7A binding was significantly upregulated in both the COC and GCs following hCG. Together these data show that Sema7a may be important during ovulation.