Ovarian follicles form through a process in which somatic pregranulosa cells encapsulate individual germ cells from germ cell syncytia. Complementary expression of the Notch ligand, Jagged1, in germ cells and the Notch receptor, Notch2, in pregranulosa cells suggests a role for Notch signaling in mediating cellular interactions during follicle assembly. Using a Notch reporter mouse, we demonstrate that Notch signaling is active within somatic cells of the embryonic ovary, and these cells undergo dramatic reorganization during follicle histogenesis. This coincides with a significant increase in the expression of the ligands, Jagged1 and Jagged2; the receptor, Notch2; and the target genes, Hes1 and Hey2. Histological examination of ovaries from mice with conditional deletion of Jagged1 within germ cells (J1 knockout [J1KO]) or Notch2 within granulosa cells (N2 knockout [N2KO]) reveals changes in follicle dynamics, including perturbations in the primordial follicle pool and antral follicle development. J1KO and N2KO ovaries also contain multi-oocytic follicles, which represent a failure to resolve germ cell syncytia, and follicles with enlarged oocytes but lacking somatic cell growth, signifying a potential role of Notch signaling in follicle activation and the coordination of follicle development. We also observed decreased cell proliferation and increased apoptosis in the somatic cells of both conditional knockout lines. As a consequence of these defects, J1KO female mice are subfertile; however, N2KO female mice remain fertile. This study demonstrates important functions for Jagged1 and Notch2 in the resolution of germ cell syncytia and the coordination of somatic and germ cell growth within follicles of the mouse ovary.

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Objective To evaluate global gene expression patterns in the common iliac arteries of monkeys with varied extent of atherosclerosis. Methods The left common iliac artery was removed from ovariectomized cynomolgus monkeys (n=12) after 6.5 years of consuming a diet containing fat and cholesterol at levels comparable to that consumed in western populations. Arterial gene expression was analyzed by DNA microarray and real time RT-PCR. Results Significant differential expression of 986 genes was observed in iliac arteries containing moderate to large atherosclerotic plaques compared to normal/minimally affected reference group arteries. Atherosclerosis-associated genes included cytokines, chemokines, components of signal transduction pathways, and transcriptional activators and repressors, as well as other functional categories. Real time RT-PCR confirmed differential expression of genes chosen from a variety of functional categories. Specifically, expression of genes for estrogen receptor 1 (ESR1), claudin 11, and BH protocadherin 7 (PCDH7) were reduced, whereas expression of genes for apolipoprotein E (ApoE), growth differentiation factor 15 (GDF15), superoxide dismutase 2 (SOD2), SET domain, bifurcated 2 (SETDB2), phospholipase A2 group IIA (PLA2IIA), phospholipase A2 group VII (PLA2VII), and ring finger protein 149 (RNF149) were increased in atherosclerotic arteries. Conclusions The gene expression environment in arteries containing atherosclerotic plaques is profoundly different from that of relatively unaffected arteries and reflects the cellular and molecular complexity of atherosclerosis and associated arterial remodeling processes.

Endometriosis, a common cause of morbidity in reproductive-age females, results in pelvic pain and infertility. Endometriosis-associated pain can be approached with surgical or medical therapies. Conservative surgery maintains reproductive organs and is effective in the treatment of endometriosis-associated pain. A more radical surgical approach of hysterectomy with bilateral salpingo-oophorectomy remains a mainstay of therapy for patients who have completed childbearing. Current medical therapies rely upon interruption of normal cyclic ovarian hormone production resulting in an environment not conducive to the growth of endometriosis. Genomics promises to further characterize endometriosis and tailor therapies based on a woman's symptoms and reproductive goals.