Long-Term In Vitro Culture Alters Gene Expression Pattern of Genes Involved in Ontological Groups Representing Cellular Processes.

The oviduct provides an optimal environment for the final preparation, transport, and survival of gametes, the fertilization process, and early embryonic development. Most of the studies on reproduction are based on in vitro cell culture models because of the cell's accessibility. It creates opportunities to explore the complexity of directly linked processes between cells. Previous studies showed a significant expression of genes responsible for cell differentiation, maturation, and development during long-term porcine oviduct epithelial cells (POECs) in vitro culture. This study aimed at establishing the transcriptomic profile and comprehensive characteristics of porcine oviduct epithelial cell in vitro cultures, to compare changes in gene expression over time and deliver information about the expression pattern of genes highlighted in specific GO groups. The oviduct cells were collected after 7, 15, and 30 days of in vitro cultivation. The transcriptomic profile of gene expression was compared to the control group (cells collected after the first day). The expression of COL1A2 and LOX was enhanced, while FGFBP1, SERPINB2, and OVGP1 were downregulated at all selected intervals of cell culture in comparison to the 24-h control (p-value < 0.05). Adding new detailed information to the reproductive biology field about the diversified transcriptome profile in POECs may create new future possibilities in infertility treatments, including assisted reproductive technique (ART) programmes, and may be a valuable tool to investigate the potential role of oviduct cells in post-ovulation events.

Cardiac progenitor cell therapy: mechanisms of action.

Heart failure (HF) is an end-stage of many cardiac diseases and one of the main causes of death worldwide. The current management of this disease remains suboptimal. The adult mammalian heart was considered a post-mitotic organ. However, several reports suggest that it may possess modest regenerative potential. Adult cardiac progenitor cells (CPCs), the main players in the cardiac regeneration, constitute, as it may seem, a heterogenous group of cells, which remain quiescent in physiological conditions and become activated after an injury, contributing to cardiomyocytes renewal. They can mediate their beneficial effects through direct differentiation into cardiac cells and activation of resident stem cells but majorly do so through paracrine release of factors. CPCs can secrete cytokines, chemokines, and growth factors as well as exosomes, rich in proteins, lipids and non-coding RNAs, such as miRNAs and YRNAs, which contribute to reparation of myocardium by promoting angiogenesis, cardioprotection, cardiomyogenesis, anti-fibrotic activity, and by immune modulation. Preclinical studies assessing cardiac progenitor cells and cardiac progenitor cells-derived exosomes on damaged myocardium show that administration of cardiac progenitor cells-derived exosomes can mimic effects of cell transplantation. Exosomes may become new promising therapeutic strategy for heart regeneration nevertheless there are still several limitations as to their use in the clinic. Key questions regarding their dosage, safety, specificity, pharmacokinetics, pharmacodynamics and route of administration remain outstanding. There are still gaps in the knowledge on basic biology of exosomes and filling them will bring as closer to translation into clinic.

Phenotypic Transitions the Processes Involved in Regulation of Growth and Proangiogenic Properties of Stem Cells, Cancer Stem Cells and Circulating Tumor Cells.

Epithelial-mesenchymal transition (EMT) is a crucial process with significance in the metastasis of malignant tumors. It is through the acquisition of plasticity that cancer cells become more mobile and gain the ability to metastasize to other tissues. The mesenchymal-epithelial transition (MET) is the return to an epithelial state, which allows for the formation of secondary tumors. Both processes, EMT and MET, are regulated by different pathways and different mediators, which affects the sophistication of the overall tumorigenesis process. Not insignificant are also cancer stem cells and their participation in the angiogenesis, which occur very intensively within tumors. Difficulties in effectively treating cancer are primarily dependent on the potential of cancer cells to rapidly expand and occupy secondarily vital organs. Due to the ability of these cells to spread, the concept of the circulating tumor cell (CTC) has emerged. Interestingly, CTCs exhibit molecular diversity and stem-like and mesenchymal features, even when derived from primary tumor tissue from a single patient. While EMT is necessary for metastasis, MET is required for CTCs to establish a secondary site. A thorough understanding of the processes that govern the balance between EMT and MET in malignancy is crucial.

Unveiling Mesenchymal Stem Cells' Regenerative Potential in Clinical Applications: Insights in miRNA and lncRNA Implications.

It is now widely recognized that mesenchymal stem cells (MSCs) possess the capacity to differentiate into a wide array of cell types. Numerous studies have identified the role of lncRNA in the regulation of MSC differentiation. It is important to elucidate the role and interplay of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in the regulation of signalling pathways that govern MSC function. Furthermore, miRNAs and lncRNAs are important clinical for innovative strategies aimed at addressing a wide spectrum of existing and emerging disease. Hence it is important to consider their impact on MSC function and differentiation. Examining the data available in public databases, we have collected the literature containing the latest discoveries pertaining to human stem cells and their potential in both fundamental research and clinical applications. Furthermore, we have compiled completed clinical studies that revolve around the application of MSCs, shedding light on the opportunities presented by harnessing the regulatory potential of miRNAs and lncRNAs. This exploration of the therapeutic possibilities offered by miRNAs and lncRNAs within MSCs unveils exciting prospects for the development of precision therapies and personalized treatment approaches. Ultimately, these advancements promise to augment the efficacy of regenerative strategies and produce positive outcomes for patients. As research in this field continues to evolve, it is imperative to explore and exploit the vast potential of miRNAs and lncRNAs as therapeutic agents. The findings provide a solid basis for ongoing investigations, fuelling the quest to fully unlock the regenerative potential of MSCs.

Small extracellular vesicles - A host for advanced bioengineering and "Trojan Horse" of non-coding RNAs.

Small extracellular vesicles (sEVs) are a type of membranous vesicles that can be released by cells into the extracellular space. The relationship between sEVs and non-coding RNAs (ncRNAs) is highly intricate and interdependent. This symbiotic relationship plays a pivotal role in facilitating intercellular communication and holds profound implications for a myriad of biological processes. The concept of sEVs and their ncRNA cargo as a "Trojan Horse" highlights their remarkable capacity to traverse biological barriers and surreptitiously deliver their cargo to target cells, evading detection by the host-immune system. Accumulating evidence suggests that sEVs may be harnessed as carriers to ferry therapeutic ncRNAs capable of selectively silencing disease-driving genes, particularly in conditions such as cancer. This approach presents several advantages over conventional drug delivery methods, opening up new possibilities for targeted therapy and improved treatment outcomes. However, the utilization of sEVs and ncRNAs as therapeutic agents raises valid concerns regarding the possibility of unforeseen consequences and unintended impacts that may emerge from their application. It is important to consider the fundamental attributes of sEVs and ncRNAs, including by an in-depth analysis of the practical and clinical potentials of exosomes, serving as a representative model for sEVs encapsulating ncRNAs.

Apoptosis Related Human Wharton's Jelly-Derived Stem Cells Differentiation into Osteoblasts, Chondrocytes, Adipocytes and Neural-like Cells-Complete Transcriptomic Assays.

Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) exhibit multilineage differentiation potential, adhere to plastic, and express a specific set of surface markers-CD105, CD73, CD90. Although there are relatively well-established differentiation protocols for WJ-MSCs, the exact molecular mechanisms involved in their in vitro long-term culture and differentiation remain to be elucidated. In this study, the cells were isolated from Wharton's jelly of umbilical cords obtained from healthy full-term deliveries, cultivated in vitro, and differentiated towards osteogenic, chondrogenic, adipogenic and neurogenic lineages. RNA samples were isolated after the differentiation regimen and analyzed using an RNA sequencing (RNAseq) assay, which led to the identification of differentially expressed genes belonging to apoptosis-related ontological groups. ZBTB16 and FOXO1 were upregulated in all differentiated groups as compared to controls, while TGFA was downregulated in all groups. In addition, several possible novel marker genes associated with the differentiation of WJ-MSCs were identified (e.g., SEPTIN4, ITPR1, CNR1, BEX2, CD14, EDNRB). The results of this study provide an insight into the molecular mechanisms involved in the long-term culture in vitro and four-lineage differentiation of WJ-MSCs, which is crucial to utilize WJ-MSCs in regenerative medicine.

Intravenous Transplantation of Adipose-Derived Mesenchymal Stem Cells Promoted The Production of Dopaminergic Neurons and Improved Spatial Memory in A Rat Model of Parkinson's Disease.

OBJECTIVE: Parkinson's disease (PD) is a neurodegenerative disorder described by the dynamic decline of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Stem cell transplantation is a new therapeutic strategy in the treatment of PD. The objective of the study was to assess the impact of intravenous infusion of adipose-derived mesenchymal stem cells (AD-MSCs) on memory disorder in Parkinsonian rats. MATERIALS AND METHODS: In this experimental study, male Wistar rats were randomly divided to four groups containing sham, cell treatment, control, and lesion. The cell treatment group received intravenous injection of AD-MSCs 12 days after PD induction by bilateral injection of 6-hydroxydopamine. Four weeks after lesion formation, spatial memory was examined using the Morris water maze (MWM) assessment. The rats' brains were removed and assessed by bromodeoxyuridine (BrdU), tyrosine hydroxylase (TH), and glial fibrillary acidic protein (Gfap) immunostaining. RESULTS: Statistical analyses revealed a significant addition and reduction in time spent and escape latency in the target quadrant, respectively, in the cell group as compared to the lesion group. Also, BrdU-labeled cells were present in the substantia nigra (SN). The density of TH-positive cells was significantly increased in the AD-MSCs transplantation group as compared to the lesion group, and the density of astrocytes significantly diminished in the AD-MSCs transplantation group as compared to the lesion group. CONCLUSION: It appears that AD-MSCs treatment for Parkinson's could decrease the density of astrocytes and promote the density of TH-positive neurons. It appears that AD-MSCs could improve spatial memory impairment in PD.

The Role of Exosomes in Human Carcinogenesis and Cancer Therapy-Recent Findings from Molecular and Clinical Research.

Exosomes are biological nanoscale spherical lipid bilayer vesicles, 40-160 nm in diameter, produced by most mammalian cells in both physiological and pathological conditions. Exosomes are formed via the endosomal sorting complex required for transport (ESCRT). The primary function of exosomes is mediating cell-to-cell communication. In terms of cancer, exosomes play important roles as mediators of intercellular communication, leading to tumor progression. Moreover, they can serve as biomarkers for cancer detection and progression. Therefore, their utilization in cancer therapies has been suggested, either as drug delivery carriers or as a diagnostic tool. However, exosomes were also reported to be involved in cancer drug resistance via transferring information of drug resistance to sensitive cells. It is important to consider the current knowledge regarding the role of exosomes in cancer, drug resistance, cancer therapies, and their clinical application in cancer therapies.

Spermatogenesis regeneration by transfected spermatogonial stem cells in infertile roosters through testicular transplantation.

Investigations pertaining to spermatogonial stem cells (SSCs) have led to the use of these cells in a variety of fields including infertility treatments, production of transgenic animals, and genome editing. The aim of the present study was to investigate the plausibility of regenerating spermatogenesis in infertile roosters by transplanting transfected SSCs into testes. Spermatogonial stem cells were isolated and cultured for seven days. Afterward, pDB2, a plasmid vector carrying a reporter gene, GFP, was transfected into the SSCs. Transfected SSCs were transplanted into the left testis of infertile roosters. Tissue samples from the recipients' testes were obtained six weeks after the transplantation and transplanted SSCs were observed in the basement membrane. After eight weeks, GFP-positive spermatozoa were observed in collected semen from the recipient roosters and GFP gene in spermatozoa was confirmed using PCR. The recipient roosters were mated with hens. Hatchlings were visually checked and their tissue samples were tested by PCR to identify transgenesis but both of them were negative. Overall, it seems that regeneration of spermatogenesis in roosters via transfected SSCs is possible but more studies are need to produce recombinant proteins by this way.

Cancer Stem Cells-The Insight into Non-Coding RNAs.

Since their initial identification three decades ago, there has been extensive research regarding cancer stem cells (CSCs). It is important to consider the biology of cancer stem cells with a particular focus on their phenotypic and metabolic plasticity, the most important signaling pathways, and non-coding RNAs (ncRNAs) regulating these cellular entities. Furthermore, the current status of therapeutic approaches against CSCs is an important consideration regarding employing the technology to improve human health. Cancer stem cells have claimed to be one of the most important group of cells for the development of several common cancers as they dictate features, such as resistance to radio- and chemotherapy, metastasis, and secondary tumor formation. Therapies which could target these cells may develop into an effective strategy for tumor eradication and a hope for patients for whom this disease remains uncurable.

The pathogenic roles of lncRNA-Taurine upregulated 1 (TUG1) in colorectal cancer.

Colorectal cancer (CRC) is a gastrointestinal tumor that develops from the colon, rectum, or appendix. The prognosis of CRC patients especially those with metastatic lesions remains unsatisfactory. Although various conventional methods have been used for the treatment of patients with CRC, the early detection and identification of molecular mechanisms associated with CRC is necessary. The scientific literature reports that altered expression of long non-coding RNAs (lncRNAs) contributed to the pathogenesis of CRC cells. LncRNA TUG1 was reported to target various miRNAs and signaling pathways to mediate CRC cell proliferation, migration, and metastasis. Therefore, TUG1 might be a potent predictive/prognostic biomarker for diagnosis of CRC.

The Potential of a Protein Model Synthesized Absent of Methionine.

Methionine is an amino acid long thought to be essential, but only in the case of protein synthesis initiation. In more recent years, methionine has been found to play an important role in antioxidant defense, stability, and modulation of cell and protein activity. Though these findings have expanded the previously held sentiment of methionine having a singular purpose within cells and proteins, the essential nature of methionine can still be challenged. Many of the features that give methionine its newfound functions are shared by the other sulfur-containing amino acid: cysteine. While the antioxidant, stabilizing, and cell/protein modulatory functions of cysteine have already been well established, recent findings have shown a similar hydrophobicity to methionine which suggests cysteine may be able to replace methionine in all functions outside of protein synthesis initiation with little effect on cell and protein function. Furthermore, a number of novel mechanisms for alternative initiation of protein synthesis have been identified that suggest a potential to bypass the traditional methionine-dependent initiation during times of stress. In this review, these findings are discussed with a number of examples that demonstrate a potential model for synthesizing a protein in the absence of methionine.

Endocrine Disrupting Chemicals in Polycystic Ovary Syndrome: The Relevant Role of the Theca and Granulosa Cells in the Pathogenesis of the Ovarian Dysfunction.

Polycystic ovary syndrome (PCOS) is the most common heterogeneous endocrine disorder among women of reproductive age. The pathogenesis of PCOS remains elusive; however, there is evidence suggesting the potential contribution of genetic interactions or predispositions combined with environmental factors. Among these, endocrine disrupting chemicals (EDCs) have been proposed to potentially contribute to the etiology of PCOS. Granulosa and theca cells are known to cooperate to maintain ovarian function, and any disturbance can lead to endocrine disorders, such as PCOS. This article provides a review of the recent knowledge on PCOS pathophysiology, the role of granulosa and theca cells in PCOS pathogenesis, and the evidence linking exposure to EDCs with reproductive disorders such as PCOS.

Mesenchymal Stem/Stromal Cells Derived from Human and Animal Perinatal Tissues-Origins, Characteristics, Signaling Pathways, and Clinical Trials.

Mesenchymal stem/stromal cells (MSCs) are currently one of the most extensively researched fields due to their promising opportunity for use in regenerative medicine. There are many sources of MSCs, of which cells of perinatal origin appear to be an invaluable pool. Compared to embryonic stem cells, they are devoid of ethical conflicts because they are derived from tissues surrounding the fetus and can be safely recovered from medical waste after delivery. Additionally, perinatal MSCs exhibit better self-renewal and differentiation properties than those derived from adult tissues. It is important to consider the anatomy of perinatal tissues and the general description of MSCs, including their isolation, differentiation, and characterization of different types of perinatal MSCs from both animals and humans (placenta, umbilical cord, amniotic fluid). Ultimately, signaling pathways are essential to consider regarding the clinical applications of MSCs. It is important to consider the origin of these cells, referring to the anatomical structure of the organs of origin, when describing the general and specific characteristics of the different types of MSCs as well as the pathways involved in differentiation.

Expression Profile of New Gene Markers and Signaling Pathways Involved in Immunological Processes in Human Cumulus-Oophorus Cells.

The function of the immune system extends from defense against external pathogens to the recognition and elimination of mutated or dying cells, aiding elimination of malignant potential and/or maintaining homeostasis. The many cell types of the immune system secrete a broad range of factors to enable cellular signaling that is vital to physiological processes. Additionally, in the ovary, follicular selection and maturation, as well as ovulation, are directly regulated by the nearby immune cells. Additionally, ovulation and rupture of the follicle have been observed to resemble a local inflammatory response. Cells of the cumulus-oocyte complex (COC) show evolving gene expression profiles throughout the oocytes' lifespan, including genes associated with immunological processes. Analysis of these genes allows the identification of useful molecular markers, as well as highlighting gene functions and interactions in these cells. Cumulus cells were obtained from hormonally stimulated patients undergoing an in vitro fertilization procedure and studied under long-term culture conditions. The microarray technique made it possible to compare the level of CCs' gene expression on the 1st, 7th, 15th and 30th day of cultivation. Additionally, RNA microarray analysis was performed to map gene expression in these cells, associated with immunological processes and associated cytokine signaling. Subsequently, the use of DAVID software allowed us to identify the "defense response to other organism", "defense response", "defense response to virus", "cytokine secretion", "cytokine production" and "cytokine-mediated signaling pathway" GO BP terms, as well as allowing further analysis of the most differentially expressed genes associated with these processes. Of the 122 genes involved, 121 were upregulated and only one was downregulated. The seven most upregulated genes related to the abovementioned terms were ANXA3, IFIT1, HLA-DPA1, MX1, KRT8, HLA-DRA and KRT18. Therefore, genes involved in immunological defense processes are upregulated in CC cultures and could serve as useful molecular markers of growth and development in the COC, as well as the proliferation of granulosa and cumulus cells.

Ovarian Cancer and Cancer Stem Cells-Cellular and Molecular Characteristics, Signaling Pathways, and Usefulness as a Diagnostic Tool in Medicine and Oncology.

Despite the increasing development of medicine, ovarian cancer is still a high-risk, metastatic disease that is often diagnosed at a late stage. In addition, difficulties in its treatment are associated with high resistance to chemotherapy and frequent relapse. Cancer stem cells (CSCs), recently attracting significant scientific interest, are considered to be responsible for the malignant features of tumors. CSCs, as the driving force behind tumor development, generate new cells by modifying different signaling pathways. Moreover, investigations on different types of tumors have shown that signaling pathways are key to epithelial-mesenchymal transition (EMT) regulation, metastasis, and self-renewal of CSCs. Based on these established issues, new therapies are being investigated based on the use of inhibitors to block CSC growth and proliferation signals. Many reports indicate that CSC markers play a key role in cancer metastasis, with hopes placed in their targeting to block this process and eliminate relapses. Current histological classification of ovarian tumors, their epidemiology, and the most recent knowledge of ovarian CSCs, with particular emphasis on their molecular background, are important aspects for consideration. Furthermore, the importance of signaling pathways involved in tumor growth, development, and metastasis, is also presented.

Human Granulosa Cells-Stemness Properties, Molecular Cross-Talk and Follicular Angiogenesis.

The ovarian follicle is the basic functional unit of the ovary, comprising theca cells and granulosa cells (GCs). Two different types of GCs, mural GCs and cumulus cells (CCs), serve different functions during folliculogenesis. Mural GCs produce oestrogen during the follicular phase and progesterone after ovulation, while CCs surround the oocyte tightly and form the cumulus oophurus and corona radiata inner cell layer. CCs are also engaged in bi-directional metabolite exchange with the oocyte, as they form gap-junctions, which are crucial for both the oocyte's proper maturation and GC proliferation. However, the function of both GCs and CCs is dependent on proper follicular angiogenesis. Aside from participating in complex molecular interplay with the oocyte, the ovarian follicular cells exhibit stem-like properties, characteristic of mesenchymal stem cells (MSCs). Both GCs and CCs remain under the influence of various miRNAs, and some of them may contribute to polycystic ovary syndrome (PCOS) or premature ovarian insufficiency (POI) occurrence. Considering increasing female fertility problems worldwide, it is of interest to develop new strategies enhancing assisted reproductive techniques. Therefore, it is important to carefully consider GCs as ovarian stem cells in terms of the cellular features and molecular pathways involved in their development and interactions as well as outline their possible application in translational medicine.

Design and Immunological Evaluation of a Hybrid Peptide as a Potent TLR2 Agonist by Structure-Based Virtual Screening.

Immunity is a versatile defensive response that is involved in protecting against disease by identifying and destroying self and non-self harmful substances. As a state of temporary or permanent immune dysfunction, immunosuppression can make an organism more susceptible to infection, organ injury, and cancer due to damage to the immune system. It has taken a long time to develop new immunomodulatory agents to prevent and treat immunosuppressive diseases. In recent years, Toll-like receptor 2 (TLR2) agonists have been reported to have profound effects on the immune system, and they are regarded as potent immunomodulatory candidates. TP5 and LL-37, the potent immunomodulatory agents, have been reported to produce a robust innate immune response by binding to TLR2. However, their development has been weakened by several concerns, such as potential cytotoxicity, weak physiological stability and poor immunomodulatory activity. To overcome these challenges, hybridization has been proposed. Therefore, six hybrid peptides (LTPa, LTPb, LTPc, TPLa, TPLb, and TPLc) were designed by combining the full-length TP5 with a characteristic fragment of LL-37 that included LL-37 (13-36), LL-37 (17-29), and LL-37 (13-31). LTPa, the most potent TLR2 agonist, was simply and effectively screened by molecular docking and in vitro experiments. Furthermore, the immunomodulatory effects of LTPa were confirmed by a CTX-immunosuppressed murine model, which demonstrated that LTPa successfully inhibit immunosuppression, increased immune organ indices, enhanced DC maturation, regulated T lymphocyte subsets, and increased cytokine and Ig contents. Our study also revealed that the immunomodulatory effects of LTPa are associated with binding to TLR2, forming TLR2 clusters, and activating the NF-κB signaling pathway.

New Gene Markers Expressed in Porcine Oviductal Epithelial Cells Cultured Primary In Vitro Are Involved in Ontological Groups Representing Physiological Processes of Porcine Oocytes.

Changes that occur within oviducts after fertilization are dependent on post-ovulation events, including oocyte-oviduct interactions. Although general processes are well-defined, the molecular basis are poorly understood. Recently, new marker genes involved in 'cell development', 'cell growth', 'cell differentiation' and 'cell maturation' processes have been identified in porcine oocytes. The aim of the study was to assess the expression profile of genes in primary in vitro cultured oviductal epithelial cells (OECs), clustered in Gene Ontology groups which enveloped markers also identified in porcine oocytes. OECs (from 45 gilts) were surgically removed and cultured in vitro for ≤ 30 days, and then subjected to molecular analyses. The transcriptomic and proteomic profiles of cells cultured during 7, 15 and 30 days were investigated. Additionally, morphological/histochemical analyzes were performed. The results of genes expression profiles were validated after using RT-qPCR. The results showed a significant upregulation of UNC45B, NOX4, VLDLR, ITGB3, FMOD, SGCE, COL1A2, LOX, LIPG, THY1 and downregulation of SERPINB2, CD274, TXNIP, CELA1, DDX60, CRABP2, SLC5A1, IDO1, ANPEP, FST. Detailed knowledge of the molecular pathways occurring in the OECs and the gametes that contact them may contribute both to developments of basic science of physiology, and new possibilities in advanced biotechnology of assisted reproduction.

Cellular Processes in Human Ovarian Follicles Are Regulated by Expression Profile of New Gene Markers-Clinical Approach.

In the growing ovarian follicle, the maturing oocyte is accompanied by cumulus (CCs) and granulosa (GCs) cells. Currently, there remain many unanswered questions about the epithelial origin of these cells. Global and targeted gene transcript levels were assessed on 1, 7, 15, 30 days of culture for CCs and GCs. Detailed analysis of the genes belonging to epithelial cell-associated ontological groups allowed us to assess a total of 168 genes expressed in CCs (97 genes) and GCs (71 genes) during long-term in vitro culture. Expression changes of the analyzed genes allowed the identification of the group of genes: TGFBR3, PTGS2, PRKX, AHI1, and IL11, whose expression decreased the most and the group of ANXA3, DKK1, CCND1, STC1, CAV1, and SFRP4 genes, whose expression significantly increased. These genes' expression indicates CCs and GCs epithelialization processes and their epithelial origin. Expression change analysis of genes involved in epithelization processes in GCs and CCs during their in vitro culture made it possible to describe the most significantly altered of the 11 genes. Detailed analysis of gene expression in these two cell populations at different time intervals confirms their ovarian surface epithelial origin. Furthermore, some gene expression profiles appear to have tumorigenic properties, suggesting that granulosa cells may play a role in cancerogenesis.