Prognostic value of E-Cadherin and its tumor suppressor role in Saudi women with advanced epithelial ovarian cancer.

The extracellular matrix (ECM) disruption and cytoskeleton reorganization are crucial events in tumor proliferation and invasion. E-Cadherin (E-CAD) is a member of cell adhesion molecules involved in cell-cell junctions and ECM stability. The loss of E-CAD expression is associated with cancer progression and metastasis. This retrospective study aimed to assess E-CAD protein expression in ovarian cancer (OC) tissues and to evaluate its prognostic value. PATIENTS AND METHODS: 143 formalin-fixed and paraffin-embedded (FFPE) blocks of primary advanced stages OC were retrieved and used to construct Tissue microarrays. Automated immunohistochemistry technique was performed to evaluate E-CAD protein expression patterns in OC. RESULTS: E-CAD protein expression was significantly correlated with OC histological subtype (p < 0.0001), while borderline significant correlations were observed with both tumor grade (p = 0.06) and stage (p = 0.07). Interestingly, Kaplan-Meier survival analysis showed that OC patients with membranous E-CAD expression survived longer than those with no E-CAD expression mainly those at advanced stages (p < 0.009). Further in silico analysis confirms the key roles of E-CAD in OC molecular functions. CONCLUSION: we reported a prognosis value of membranous E-CAD in advanced stage OC patients. Further validation using larger cohorts is recommended to extract clinically relevant outcomes towards better OC management and individualized oncology.

Determination of in vivo biological activities of Dodonaea viscosa flowers against CCL4 toxicity in albino mice with bioactive compound detection.

Dodonaea viscosa L.Jacq. is an evergreen shrub and native to Asia, Africa, and Australia. It has been used as traditional medicine in different countries. The foremost objective of the current study was to discover the protective potential of D. viscosa flowers Methanol (DVM) and Chloroform (DVC) extracts against CCL4 induced toxicity in mice. This study was intended to identify phytochemicals through HPLC, GCMS, and FT-IR, as well as in vitro antioxidant and in vitro anti-tuberculosis activity. Our comprehensive findings indicate that Dodonaea viscosa is valuable and widespread herbal medicine through therapeutic potentials for curing various ailments. Dodonaeaviscosa flowersare found to have a protective effect against oxidative stress produced by CCL4 in the liver, kidney, and spleen. The intake of DV extracts restored the level of hepatic enzymes (ALP, AST ALT, and Direct bilirubin), hematological parameters (RBCs, WBCs, and Platelets), total protein, and liver antioxidant enzymes (SOD, GPx, and CAT) after a decline in levels by CCL4. Histopathological results discovered the defensive effect of 300 mg/kg of DVM extract against CCL4 induced damage, thus having an improved protective effect compared to DVC and control. As a result of metabolite screening, the total flavonoids and total phenolics were present in abundance. A phytochemical investigation by HPLC identified gallic acid, epicatechin, cumeric acid, flavonoids, while GCMS estimated oleic acid (Octadecenoic acid) (C18H34O2), Stearic acid (C18H36O2), Ricinoleic acid (C18H34O3), and Cedrol (C15H26O). DVM extract exhibited resistance against in vitro Mycobacterium tuberculosis strains. So this study proposed that the protective effect of DV against oxidative damage induced in the liver, kidney, and spleen can be correlated to the antioxidant compounds.

Identification of Lead Compounds against Scm (fms10) in Enterococcus faecium Using Computer Aided Drug Designing.

(1) Background: Enterococcus faecium DO is an environmental microbe, which is a mesophilic, facultative, Gram-positive, and multiple habitat microorganism. Enterococcus faecium DO is responsible for many diseases in human. The fight against infectious diseases is confronted by the development of multiple drug resistance in E. faecium. The focus of this research work is to identify a novel compound against this pathogen by using bioinformatics tools and technology. (2) Methods: We screened the proteome (accession No. PRJNA55353) information from the genome database of the National Centre for Biotechnology Information (NCBI) and suggested a potential drug target. I-TASSER was used to predict the three-dimensional structure of the protein, and the structure was optimized and minimized by different tools. PubChem and ChEBI were used to retrieve the inhibitors. Pharmacophore modeling and virtual screening were performed to identify novel compounds. Binding interactions of compounds with target protein were checked using LigPlot. pkCSM, SwissADME, and ProTox-II were used for adsorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. (3) Results: Novel selected compounds have improved absorption and have better ADMET properties. Based on our results, the chemically identified inhibitor ZINC48942 targeted the receptor that can inhibit the activity of infection in E. faecium. This research work will be beneficial for the scientific community and could aid in the design of a new drug against E. faecium infections. (4) Conclusions: It was observed that novel compounds are potential inhibitors with more efficacy and fewer side effects. This research work will help researchers in testing and identification of these chemicals useful against E. faecium.

Effect of Nandrolone decanoate induced-oxidative stress on rat testes, prostate, and seminal vesicle: Biochemical, morphometric and histopathological studies.

Nandrolone decanoate (Nd) is a highly abused androgenic-anabolic steroid among body builders. Even though it has weak androgenic effects, its prolonged use may have harmful impact on male reproductive system which needs to be evaluated. This study aimed to reinvestigate its possible oxidative stress induced alteration on male rat reproductive system. Twenty-eight male rats were divided into two groups. Nd treated group (n = 18) injected intramuscular with 10 mg/kg body weight once a week for four weeks. While, the control group (n = 10) was injected with physiologic saline by the same route for four weeks. Body weight was recorded for all rats and after animal dissection weight of testes, prostate and seminal vesicles were also recorded. The results showed that the average testicular weight was decreased in treated group compared to the control. The average weights of the prostate and seminal vesicles were increased compared to the control. Morphometric study revealed that in Nd treated group, there was a decrease in the width of seminiferous tubules and the height of spermatogenic cell layer compared to the control. Testicular degeneration was expressed by presence of spermatid giant cells, vacuolation, and degenerated spermatozoa. Tunnel technique showed scattered positive reaction among the spermatogenic cell layers and interstitial cells. Severe alterations of the prostate were expressed by benign prostate hyperplasia and retained secretions. Lipid peroxidation products (malonaldehyde concentration as ng/g of testicular tissue) were increased in treated group compared to the control and suggested the occurrence of oxidative damage. Nd induced severe alterations in the male genital organs were resulted from oxidative stress. It is concluded that the male genital organs are highly sensitive to the anabolic steroids and there is a high extent of reproductive risk associated with the use of AASs.

Quantification of biochemical compounds in Bauhinia Variegata Linn flower extract and its hepatoprotective effect.

Liver disorders may occur as a result of exposure to chemical compounds capable of inducing the oxidative stress and hepatic injuries. The aim of present study was to investigate the effects of flower extracts of B. Variegata for the treatment of liver injury induced by the CCl4. About 1 ml/kg body weight (b.w) of CCl4 was induced to experimental mice by intraperitoneal way for 14 days. The methanol and chloroform extracts (100, 200 and 300 mg/kg b.w) were administered to experimental animals for 14 days along with standard drug Silymarine (100 mg/kg b.w). The extracts alone showed no evidence of hepatic toxicity but animals exposed to CCl4 without the treatment with B. Variegata presented variations in levels of liver enzymes, antioxidant enzymes, proteins and blood cells as well as injuries in liver cells were also observed during histopathological study. However, after the treatments especially with 300 mg/kg b.w of methanol flower extracts levels of liver markers (ALT, AST and ALP), antioxidant enzymes and blood cells decreases and turned towards normal levels. Whereas level of total proteins and bilirubin was improved and damaged liver cells were repaired. The curative activity of flower extracts can be correlated to the higher potential of antioxidants and occurrence of Quercetin and some other organic compounds those were investigated from flower extracts of B. Variegata during HPLC and GC-MS analysis. The finding of this study supports the use of B. Variegata flower formulation in folk medicines.

BMT: Bioinformatics mini toolbox for comprehensive DNA and protein analysis.

Background Bioinformatics tools are of great significance and are used in different spheres of life sciences. There are wide variety of tools available to perform primary analysis of DNA and protein but most of them are available on different platforms and many remain undetected. Accessing these tools separately to perform individual task is uneconomical and inefficient. Objective Our aim is to bring different bioinformatics models on a single platform to ameliorate scientific research. Hence, our objective is to make a tool for comprehensive DNA and protein analysis. Methods To develop a reliable, straight-forward and standalone desktop application we used state of the art python packages and libraries. Bioinformatics Mini Toolbox (BMT) is combination of seven tools including FastqTrimmer, Gene Prediction, DNA Analysis, Translation, Protein analysis and Pairwise and Multiple alignment. Results FastqTrimmer assists in quality assurance of NGS data. Gene prediction predicts the genes by homology from novel genome on the basis of reference sequence. Protein analysis and DNA analysis calculates physiochemical properties of nucleotide and protein sequences, respectively. Translation translates the DNA sequence into six open reading frames. Pairwise alignment performs pairwise global and local alignment of DNA and protein sequences on the basis or multiple matrices. Multiple alignment aligns multiple sequences and generates a phylogenetic tree. Conclusion We developed a tool for comprehensive DNA and protein analysis. The link to download BMT is https://github.com/nasiriqbal012/BMT_SETUP.git.

Identifying genes associated with the development of human polycystic ovary syndrome.

The pathophysiology of polycystic ovary syndrome (PCOS) is confusing until today as it is a multifactorial endocrine disorder. It is presented with altered gonadotropin levels, bulky multi-follicular ovaries, infertility, and obesity. This complex pathophysiology is linked with insulin resistance and hyperandrogenism. Hyperandrogenemia significantly contributes towards cosmetic anomalies including hirsutism, acne, and alopecia in the PCOS women. The preexisting insulin resistance in women with PCOS is likely to aggravate the increased levels of androgen. The review findings have shown that in the steroidogenic pathway, ovarian steroidogenesis patterns classify mainly towards the hypertrophy of theca cells along with alteration in the expression of key enzymes. The association of polymorphisms in genes encoding the process of an intricate cascade of steroidogenesis is delineated. The emergence of an unanimously accepted genetic marker for susceptible PCOS was affected based on inconsistent findings. The present study has provided a comprehensive summary of the impact of polymorphisms among the common androgen-related genes to govern the genetic predisposition.

Hormonal and molecular alterations induced by sub-lethal toxicity of zinc oxide nanoparticles on Oreochromis niloticus.

This study was carried out to determine the biochemical and molecular potential effects of Zn-ONPs sub-lethal toxicity on the hormonal profile of Oreochromis niloticus (O. niloticus). One hundred and fifty O. niloticus juvenile female were used in this experiment; Ninety for determination of LC50 and other 60 fish were divided into 3 groups with 20 fish each (two replicate in each group). Group I used as control group whereas other groups treated with 1/20 and 1/30 of LC50 respectively for 4 days. Serum, pituitary gland, hepatic, pancreatic and muscular tissues were obtained for hormonal and molecular evaluation. Serum growth hormone (GH), thyroid stimulating hormone (TSH), triiodothyronine (T3), tetraiodothyronine (T4), follicular stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone and insulin hormones were significantly decreased with a significant increase in both Adrenocorticosteroid hormone (ACTH) and cortisol levels with no change in serum glucagon levels. On molecular levels there were a significant down regulation in transcriptional levels of GH, Insulin like growth factor I (IGF-I), insulin and Insulin receptor-A (IRA genes. These results suggested that, hormonal and molecular alterations can be used as an early biomarkers for Zn-ONPs toxicity in fish.

Panax ginseng improves glucose metabolism in streptozotocin-induced diabetic rats through 5' adenosine monophosphate kinase up-regulation.

5' AMP-activated protein kinase (AMPK), insulin receptors and transporters are distorted in diabetes mellitus. In this study, the effect of Panax ginseng was assessed on glucose manipulating enzymes activities and gene expression of AMPK, IRA and GLUT2 in streptozotocin-induced diabetic male rats. Forty male albino rats were randomly divided to four groups 10 rats of each, group I, normal control group (received saline orally); group II, normal rats received 200 mg/kg of Panax ginseng orally; group III, Streptozotocin (STZ) -induced diabetic rats and group IV, STZ-induced diabetic rats received 200 mg/kg of Panax ginseng orally. The duration of experiment was 30 days. Results showed the ability of Panax ginseng to induce a significant decrease in the blood glucose and increase in the serum insulin levels, hepatic glucokinase (GK), and glycogen synthase (GS) activities with a modulation of lipid profile besides high expression levels of AMPK, insulin receptor A (IRA), glucose transporting protein-2 (GLUT-2) in liver of diabetic rats. In conclusion, the obtained results point to the ability of Panax ginseng to improve the glucose metabolism in diabetic models.

The impact of nandrolone decanoate administration on ovarian and uterine tissues in rat: Luteinizing hormone profile, histopathological and morphometric assessment.

The study had been conducted to evaluate the effects of nandrolone decanoate (abused repeated doses) on female rat's ovary and uterus during administration and withdrawal. The study included 18 rats that were divided into control group (n = 6) and treated group (n = 12). The treated group was injected intramuscular (IM) with nandrolone decanoate (7 mg/kg body weight) for three consecutive days, for two weeks. The study stated that nandrolone decanoate increases the weights of body, ovary, and uterus. Moreover, it has a tendency of bringing upon modifications in the biochemical, histopathological, and morphological makeup of the female reproductive aspects. In conclusion, nandrolone decanoate has been identified as deleterious element for the female rats, and it is suggested that keen observations must be made on the human abusers to control and manage the possible pathologies.

Assessment of knowledge about biobanking among healthcare students and their willingness to donate biospecimens.

BACKGROUND: Biobanks and biospecimen collections are becoming a primary means of delivering personalized diagnostics and tailoring individualized therapeutics. This shift towards precision medicine (PM) requires interactions among a variety of stakeholders, including the public, patients, healthcare providers, government, and donors. Very few studies have investigated the role of healthcare students in biobanking and biospecimen donations. The main aims of this study were (1) to evaluate the knowledge of senior healthcare students about biobanks and (2) to assess the students' willingness to donate biospecimens and the factors influencing their attitudes. METHODS: A cross-sectional study was conducted among senior healthcare students at King Abdulaziz University (KAU), Saudi Arabia. The data were obtained using a self-administered questionnaire in English. In addition to the respondents' biographical data section, the questionnaire assessed the respondents' general knowledge about biobanking, the factors influencing their willingness to donate biospecimens to biobanks and their general attitudes towards biomedical research. RESULTS: A total of 597 senior healthcare students were included in the study. The general knowledge score was 3.2 (±1.6) out of 7. Only approximately 44% and 27% of students were aware of the terms "Human Genome Project" (HGP) and "biobank," respectively. The majority of the students (89%) were willing to donate biospecimens to biobanks. Multiple factors were significantly associated with their willingness to donate, including their perceived general health (p < 0.001), past experience with both tissue testing (p < 0.04) and tissue donation (p < 0.001), biobanking knowledge score (p < 0.001) and biomedical research attitude score (p < 0.001). The main reasons for students' willingness to donate were advancement of medical research and societal benefits, whereas misuse of biospecimens and confidentiality breaches were the main reasons for a reluctance to donate. CONCLUSION: Despite their strong willingness to donate biospecimens, students exhibited a notable lack of knowledge about biobanking and the HGP. To expedite the transition towards PM, it is highly recommended to enhance healthcare curricula by including more educational and awareness programmes to familiarize students with OMICs technologies in addition to the scope of research and clinical applications.

Effect of Zinc nanoparticles on oxidative stress-related genes and antioxidant enzymes activity in the brain of Oreochromis niloticus and Tilapia zillii.

This study was carried out to determine the median lethal concentrations (LC50) of Zinc nanoparticles (ZnNPs) on Oreochromis niloticus and Tilapia zillii. The biochemical and molecular potential effects of ZnNPs (500 and 2000 µg L-1) on the antioxidant system in the brain tissue of O. niloticus and T. zillii were investigated. Four hundred fish were used for acute and sub-acute studies. ZnNP LC50 concentrations were investigated in O. niloticus and T. zillii. The effect of 500 and 2000 µg L-1 ZnNPs on brain antioxidants of O. niloticus and T. zillii was investigated. The result indicated that 69 h LC50 was 5.5 ± 0.6 and 5.6 ± 0.4 for O. nilotica and T. zillii, respectively. Fish exposed to 500 µg L-1 ZnNPs showed a significant increase in reduced glutathione (GSH), total glutathione (tGSH) levels, superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activity and gene expression. On the contrary, malondialdehyde (MDA) levels significantly decreased. Meanwhile, fish exposed to 2000 µg L-1 ZnNPs showed a significant decrease of GSH, tGSH levels, SOD, CAT, GR, GPx and GST activity and gene expression. On the contrary, MDA levels significantly increased. It was concluded that, the 96 h LC50 of ZnNPs was 5.5 ± 0.6 and 5.6 ± 0.4 for O. nilotica and T. zillii, respectively. ZnNPs in exposure concentrations of 2000 µg/L induced a deleterious effect on the brain antioxidant system of O. nilotica and T. zillii. In contrast, ZnNPs in exposure concentrations of 500 µg L-1 produced an inductive effect on the brain antioxidant system of O. nilotica and T. zillii.

Toxicity of silver nanoparticles on the brain of Oreochromis niloticus and Tilapia zillii.

BACKGROUND: Silver nanoparticles (Ag-NPs) are widely used nowadays in a variety of commercial applications including medical, health care, textiles and household supplies. OBJECTIVES: The current study was designed to determine the median lethal dose (LC50) of Ag-NPs on Oreochromis niloticus and Tilapia zillii. METHODS: Acute and sub-acute toxicity study of the Ag-NPs on brain tissues was carried out using different concentrations of the NPs at 2 mg L and 4 mg L. These concentrations were dispersed in deionized water with the exception of the control groups in the experiments. Biochemical and molecular analysis were conducted on tissue homogenates in order to evaluate the potential effects of NPs on the antioxidant system. RESULTS: The Ag-NP acute toxicity (96 h LC50) values of 19.5 ± 2 and 20 ± 2.4 mg/L were reported for O. niloticus and T. zillii respectively. Fish exposed to 2 mg/L Ag-NPs did not show any significant change in the levels of reduced glutathione (GSH), total glutathione (tGSH) levels, superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activity or genes expression and malondialdehyde (MDA) level. In contrary, a dose of 4 mg/L showed a significant reduction in the levels all the above-mentioned parameters except in MDA level where it was significantly induced. CONCLUSION: Results indicate that exposure of O. niloticus and T. zillii to Ag-NPs (4 mg/L) has deleterious effects on brain antioxidant system, whereas a dose of 2 mg/L has no effects.

Light and Transmission Electron Microscopic Studies on Subacute Toxicity of Bisphenol A on the Rat Ovary.

OBJECTIVE: To investigate subacute toxicity of Bisphenol A (BPA) in adult rat ovaries using gastric intubation daily for 4 weeks by light and transmission electron microscopy. STUDY DESIGN: Fifteen rats were included in the study and divided into 2 groups: 12 rats were used for BPA administration (600 mg/kg body weight), and 3 rats received only vehicle and served as controls. The ovaries of both treated and control rats were taken at 1, 2, 3, and 4 weeks postadministration, fixed in 10% neutral buffered formalin, and processed for light microscopy. Ovarian samples at the 4th week postexposure were fixed in 3% glutaraldehyde and processed for transmission electron microscopy. RESULTS: The main histopathological alterations were observed at the 3rd and 4th weeks postexposure. Atretic follicles,formation of cysts, separation of granulosa cells, and hyperemia of blood vessels were observed. Moreover, a marked increase in the thickness of the tunica albuginea was determined (33.8 ± 1.72 µm and 34.8 ± 1.72 µm, respectively,for the 3rd and 4th weeks as compared to the control group (13.78 ± 0.12 µm). Transmission electron microscopy showed marked lipid droplet accumulation, chromatin condensation in the nuclei of granulosa cells, and presence of autophagosomes in the treated group at 4 weeks postexposure as compared to the nonexposed group (control group). CONCLUSION: The results of the present study suggest altered or disrupted ovulation. Moreover, change in the thickness of the tunica albuginea observed during the course of exposure may play a role in such disrupted ovulation.

Angiotensin converting enzyme gene polymorphism studies: A case-control study.

Mild gestational hyperglycemia (MGH) is a very common complication of pregnancy that is characterized by intolerance to glucose. The association of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism to MGH has been previously reported. In this study, we evaluated the association between ACE polymorphism and the risk of MGH in a Saudi population. We conducted a case-control study in a population of 100 MGH patients and 100 control subjects. ACE gene polymorphism was analyzed by the novel approach of tetraprimer amplification refractory mutation system (ARMS)-polymerase chain reaction (PCR). The frequency of ACE polymorphism was not associated with either alleles or genotypes in MGH patients. Glucose concentration was found to be significantly associated with the MGH group. Our study suggests that ACE genotypes were not associated with ACE polymorphism in a Saudi population.

Ovarian surface epithelium receptors during pregnancy and estrus cycle of rats with emphasis on steroids and gonadotropin fluctuation.

The present study is designed to demonstrate the ovarian surface epithelial cells' (OSE) estrogen receptor α (ERα) and progesterone receptor (PR) during pregnancy and estrous cycle in rat. Moreover, determination of the levels of plasma progesterone, estradiol, FSH and LH was also made. The levels of plasma progesterone, estradiol, FSH and LH concentrations were determined on days 7 (n = 5), 14 (n = 5), and 21 (n = 5) of pregnancy in three groups of rats and during the estrous cycle (n = 5) using an ELISA kit. Immunohistochemical method for PR and ERα expressions was also made on the ovary. During pregnancy, FSH and LH remained low except at term when LH levels began to increase from 16 ng/ml to 47 ng/ml. Progesterone levels significantly exceeded estradiol values in all pregnant rats with a peak value of 202 ng/ml on day 14. Elevated progesterone levels were associated negatively with LH and estradiol levels during pregnancy. The levels of estradiol surged significantly on day 21. Immunohistochemistry of the ovary showed low levels of OSE cells staining positive for ERα expression. ERα positive cells were absent on day 7 and 14 of pregnancy, only day 21 recorded a very low percentage of immunostaining (0.5%) within the nuclei of OSE cells. On the contrary, immunostaining of PR was not observed within the nuclei of OSE cells in all groups of study. In conclusion, these results may suggest that the progesterone effect during pregnancy seems to be overriding the positive effect of estrogens on OSE cells. High progesterone levels may have a direct negative effect on gonadotropin production and thereby it might inhibit events leading to both follicular development and OSE proliferation. Understanding the factors affecting OSE proliferation may help elucidating the mechanism(s) of assisted diseases such as ovarian cancer.

In vivo and in vitro studies on apoptosis in OSE cells and inclusion cysts of pregnant heifers.

Elevated progesterone concentration during pregnancy and use of progesterone-like contraceptives are known to reduce ovarian cancers. This study was undertaken to decipher whether or not there is any relationship between progesterone (also oestrogen)-mediated ovarian surface epithelium (OSE) apoptosis and expression of p53, a cell-cycle arresting protein and potential tumour suppressor. Immunohistochemical staining with cytokeratin confirmed epithelial nature of the cells in the OSE layer and inclusion cysts that invaginate inside stroma after ovulation takes place. The in situ apoptosis index was determined during oestrus, and at mid and late-pregnancy stages in heifers. Epithelia of both tissues exhibited significantly high nuclear staining, suggesting that these cells are aiming to apoptotic destruction. To further establish a role of progesterone, the OSE cells were exposed in vitro to two concentrations of oestrogen and progesterone. It was revealed that progesterone at both concentrations and oestrogen only at high concentration converted a large proportion of these cells apoptotic. The stimulatory effect of progesterone (and to some extent oestrogen) was also seen on p53 expression in the same cultivated OSE cells. The steroid dosage dependence for apoptosis and p53 expression was also somewhat similar. Assuming that progesterone action is mediated through p53-caused apoptosis as a mechanism to evade malignant transformation of OSE cells, p53 expression at mRNA and protein level was investigated in the OSE layer in proximity to stroma, antrum and corpus luteum (CL). In cycling animals CL produces a large amount of progesterone and also oestrogen to maintain the post-ovulatory cycle and to suppress the gonadotropin production. Hence, cells undergoing re-epithelialization and which are in contact with CL were expected to undergo maximum apoptotic modification. Indeed we got the maximum p53/p53 gene expression in these cells. We conclude that progesterone during cycling and pregnancy may reduce the risk of developing ovarian cancer by ceasing cell cycle and diverting damaged and mutagenized OSE cells for apoptosis, and the process may be mediated through elevated p53 synthesis. However, it is also possible that progesterone and p53-induced apoptosis may be entirely different cancer suppressive actions but coincidently happening together.

In vitro regulation of sheep ovarian surface epithelium (OSE) proliferation by local ovarian factors.

The ovarian surface epithelium (OSE) forms a lining around the entire ovary and actively participates in the ovulatory cycle. To investigate how specific growth factors and hormones affect OSE proliferation, the present study used sheep as a model to examine the effects of follicular and luteal products on the proliferation of sheep OSE cells in culture, and to analyse the influences of large antral follicles and corpora lutea (CL) on the expression of gonadotrophin receptors (FSHR and LHR) in the OSE. In the present study, follicular fluids from medium and large follicles, and extracts of corpora lutea stimulated the growth of OSE cells. The results of the present study showed that factors in the follicular fluid can induce OSE proliferative activity, and this stimulation effect could not be attributed to steroids in the follicular fluid since oestrogen and progesterone treatments failed to stimulate OSE cells. The expression of LH and FSH receptors over large follicles (5 mm or larger) was two and four times higher than those over stroma and CL, respectively. In conclusion, OSE proliferation in cycling sheep is associated with underlying developing follicles and CL, mediated by, at least in part, the up-regulation of gonadotrophin receptors, and facilitated by the action of mitogenic glycopeptides and growth factors, but not steroids.