Mouse ovary developmental RNA and protein markers from gene expression profiling

Herrera, Luisa; Ottolenghi, Chris; Garcı́a-Ortiz, José Elı́as; Pellegrini, Massimo; Manini, Francesca; Ko, Minoru S.H.; Nagaraja, Ramaiah; Forabosco, Antonino; Schlessinger, David

doi:10.1016/j.ydbio.2004.11.029

Cited by 55 publications

(36 citation statements)

References 98 publications

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“…Thus, DNp63 is not required for cisplatin-induced oocyte death primary follicles. [43][44][45][46] However, because c-Abl was induced by cisplatin in a TAp63-dependent manner, we hypothesize that c-Abl is the target of imatinib in its fertoprotective effects on primordial follicles (Figure 7). Further studies are needed to identify the precise mechanism, through which imatinib exerts its fertoprotective effect against cisplatin.…”

Section: Discussionmentioning

confidence: 98%

Rescue of platinum-damaged oocytes from programmed cell death through inactivation of the p53 family signaling network

Cordeiro²,

et al. 2013

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Non-proliferating oocytes within avascular regions of the ovary are exquisitely susceptible to chemotherapy. Early menopause and sterility are unintended consequences of chemotherapy, and efforts to understand the oocyte apoptotic pathway may provide new targets for mitigating this outcome. Recently, the c-Abl kinase inhibitor imatinib mesylate (imatinib) has become the focus of research as a fertoprotective drug against cisplatin. However, the mechanism by which imatinib protects oocytes is not fully understood, and reports of the drug's efficacy have been contradictory. Using in vitro culture and subrenal grafting of mouse ovaries, we demonstrated that imatinib inhibits the cisplatin-induced apoptosis of oocytes within primordial follicles. We found that, before apoptosis, cisplatin induces c-Abl and TAp73 expression in the oocyte. Oocytes undergoing apoptosis showed downregulation of TAp63 and upregulation of Bax. While imatinib was unable to block cisplatin-induced DNA damage and damage response, such as the upregulation of p53, imatinib inhibited the cisplatin-induced nuclear accumulation of c-Abl/TAp73 and the subsequent downregulation of TAp63 and upregulation of Bax, thereby abrogating oocyte cell death. Surprisingly, the conditional deletion of Trp63, but not DNp63, in oocytes inhibited apoptosis, as well as the accumulation of c-Abl and TAp73 caused by cisplatin. These data suggest that TAp63 is the master regulator of cisplatin-induced oocyte death. The expression kinetics of TAp63, c-Abl and TAp73 suggest that cisplatin activates TAp63-dependent expression of c-Abl and TAp73 and, in turn, the activation of TAp73 by c-Abl-induced BAX expression. Our findings indicate that imatinib protects oocytes from cisplatin-induced cell death by inhibiting c-Abl kinase, which would otherwise activate TAp73-BAX-mediated apoptosis. Thus, imatinib and other c-Abl kinase inhibitors provide an intriguing new way to halt cisplatin-induced oocyte death in early follicles and perhaps conserve the endocrine function of the ovary against chemotherapy.

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Section: Discussionmentioning

confidence: 98%

Rescue of platinum-damaged oocytes from programmed cell death through inactivation of the p53 family signaling network

Cordeiro²,

et al. 2013

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“…Both microarray and real-time PCR data confirmed the reduction in BMP4 and GDF9 Other extracellular signaling factors that changed with AMH treatment have previously been identified in ovaries, but have not been shown to be involved in follicle transition. These include Bambi (Loveland et al 2003), Fstl (Herrera et al 2005), Mif (Suzuki et al 1996, Wada et al 1997, Bove et al 2000, Ostrer 2000, Matsuura et al 2002, Saitoh 2003, TGFb2 (Nilsson et al 2001b, Gueripel et al 2004, Itga6 (Terpe et al 1994, Frojdman & Pelliniemi 1995, Fujiwara et al 1995, Giebel et al 1996, Zuccotti et al 1998, Burns et al 2002, Le Bellego et al 2005, and VEGF (Lam & Haines 2005, Fraser 2006). These are now interesting candidate genes and experiments will be needed to determine whether these factors have any role in primordial to primary follicle transition.…”

Section: Mechanisms Of Amh Actionmentioning

confidence: 99%

Actions of anti-Müllerian hormone on the ovarian transcriptome to inhibit primordial to primary follicle transition

Nilsson¹,

Rogers²,

Skinner³

2007

Reproduction

169

102

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The oocytes found within the primordial follicles of mammalian ovaries remain quiescent for months to years until they receive the appropriate signals to undergo the primordial to primary follicle transition and initiate folliculogenesis. The molecular mechanisms and extracellular signaling factors that regulate this process remain to be fully elucidated. The current study investigates the mechanisms utilized by anti-Mü llerian hormone (AMH; i.e. Mü llerian inhibitory substance) to inhibit the primordial to primary follicle transition. Ovaries from 4-day-old rats were placed into organ culture and incubated in the absence or presence of AMH, either alone or in combination with known stimulators of follicle transition, including basic fibroblast growth factor (bFGF), kit ligand (KITL), or keratinocyte growth factor (KGF). Following 10 days of culture, the ovaries were sectioned, stained, and morphologically evaluated to determine the percentage of primordial versus developing follicles. As previously demonstrated, AMH treatment decreased primordial to primary follicle transition. Interestingly, AMH inhibited the stimulatory actions of KITL, bFGF, and KGF. Therefore, AMH can inhibit the basal and stimulated development of primordial follicles. To investigate the mechanism of AMH actions, the influence AMH has on the ovarian transcriptome was analyzed. AMH treatment when compared with controls was found to alter the expression of 707 genes. The overall effect of AMH exposure is to decrease the expression of stimulatory factors, increase the expression of inhibitory factors, and regulate cellular pathways (e.g. transforming growth factor b signaling pathway) that result in the inhibition of primordial follicle development. Analysis of the regulatory factors and cellular pathways altered by AMH provides a better understanding of the molecular control of primordial follicle development.

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“…Normal OSE also express a-and b-catenin (Davies et al 1998), as well as a number of growth factors, including amphiregulin, and express receptors for epidermal growth factor, ovarian hormones, gonadotrophins, and hepatocyte growth factor/scatter factor (Johnson et al 1991, Gulati & Peluso 1997, Auersperg et al 2001. Although extensive genomic studies of the whole ovary (Espey & Richards 2002, Rinn et al 2004, Zhang et al 2004, Herrera et al 2005 or various components, such as oocytes (Kocabas et al 2006) and granulosa cells at various stages of development have been conducted, the limited material and delicate nature of the OSE has been a major barrier to studying OSE genomics using high throughput techniques, such as microarrays. Attempts have been made to address these problems using ovarian epithelial cells maintained in short-term cultures or immortalized cell lines, however Zorn et al (2003) found that the gene expression profiles of cultured and immortalized cell lines are quite different compared with normal ovarian epithelial cell brushings, and thus may not accurately represent the phenotype of their cell of origin.…”

Section: Introductionmentioning

confidence: 99%

Global gene expression profiles of ovarian surface epithelial cells in vivo

Gava

Bye

deFazio

2008

Journal of Molecular Endocrinology

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Epithelial ovarian cancer, the leading cause of death from gynecological malignancy in Western countries, is thought to arise from the ovarian surface epithelium (OSE). It has been postulated that the constant rounds of proliferation and repair following ovulation contributes to neoplastic transformation. However, there is little information on the genes and pathways which are involved in the normal functions of the ovarian epithelium, in particular genes that are hormone responsive and those central to functions such as proliferation and apoptosis during ovulation. We used laser microdissection and cDNA microarrays to profile gene expression specifically in mouse ovarian epithelial cells, first compared with other ovarian cells, and secondly between ovarian epithelium collected at different physiological stages. We identified over 1000 transcripts that were consistently more highly expressed in the ovarian epithelium compared with remaining ovarian cell types, including genes involved in cell growth, transcription, and cell adhesion. At the various physiological stages examined, the highest number of regulated genes was found during the estrous cycle, specifically on the evening of proestrus, coincident with the ovulatory surge of hormones and just prior to ovulation. The expression of several selected genes, identified by the microarray analysis, including Villin 2, Keratin 8, Arginine-rich mutated in epithelial tumors, and Tumor-associated calcium signal transducer 1, was validated by independent methods. The identification of genes expressed and regulated in the OSE, and characterization of the pathways involved, will contribute to a more detailed understanding of the ovarian epithelium transcriptome and ultimately lead to a better understanding of the aberrations leading to malignant transformation in the ovarian epithelium.

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Mouse ovary developmental RNA and protein markers from gene expression profiling

Cited by 55 publications

References 98 publications

Rescue of platinum-damaged oocytes from programmed cell death through inactivation of the p53 family signaling network

Rescue of platinum-damaged oocytes from programmed cell death through inactivation of the p53 family signaling network

Actions of anti-Müllerian hormone on the ovarian transcriptome to inhibit primordial to primary follicle transition

Global gene expression profiles of ovarian surface epithelial cells in vivo

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