Roxani Angelopoulou - Academia.edu (original) (raw)
Papers by Roxani Angelopoulou
Collegium antropologicum, 2015
Cardiovascular disease shows a distinct difference in incidence rates between men and women, a fa... more Cardiovascular disease shows a distinct difference in incidence rates between men and women, a fact that has been known for many years. While initial theories supported that this could be attributed to the protective effect of estrogens in women, attempts to correlate endogenous estrogen levels with cardiovascular risk factors and the progression of atherosclerosis-related indexes indicate otherwise. Similarly, endogenous androgen levels seem to correlate with opposite effects in males and females, whereas exogenous treatment with either androgens or estrogens fails to correspond to scientific expectations entirely. A brief discussion of the merits and pitfalls of placing either estrogens or androgens alone at the root of the problem shows that current understanding is inadequate concerning this major anthropological issue, as it refers to the primary global mortality and morbidity cause.
Collegium antropologicum, 2013
Sexual dimorphism is a characteristic of a large number of species, ranging from lower invertebra... more Sexual dimorphism is a characteristic of a large number of species, ranging from lower invertebrates to mammals and, last but not least, humans. Recognition of the various factors regulating sexual dimorphism initial establishment (i.e. sex determination and differentiation) and subsequent life-long adaptation to distinct functional and behavioural patterns has remained a hot topic for several decades. As our understanding of the various molecular pathways involved in this process increases, the significant role of sex steroids becomes more evident. At the same time, the recognition of new sites of steroid production (e.g. parts of the brain) and aromatization, as well as new target cells (owing to the proposed presence of additional receptors to those classically considered as primary steroid receptors) has lead to the need to revisit their spectrum of actions within a novel, multifactorial context. Thus, anthropology and medicine are presented with the challenge to unravel a major...
Collegium antropologicum, 2013
Anthropology has always been particularly interested in the origin of human life and the developm... more Anthropology has always been particularly interested in the origin of human life and the development towards adulthood. Although originally working with skeletal measurements and bio-morphological markers in modern populations, it has now entered the growing field of applied molecular biology. This relatively recent advance allows the detailed study of major events in human development and senescence. For instance, sperm DNA integrity and chromatin re-organization are crucial factors for fertilization and embryo development. Clinical researchers have developed improved methods for the evaluation of DNA integrity and protaminosis in sperm nuclei, such as the TUNEL and the CMA3 assays. DNA damage in spermatozoal nuclei is detected using the TUNEL assay which depends on the specific enzymatic reaction of TdT with the end strand breaks of DNA. Protaminosis in spermatozoal nucleus is evaluated using CMA3 assay, which is based on the in situ competition between CMA3 and protamines. Such m...
Hellenic journal of nuclear medicine
Liver regeneration involves a significant variety of growth and paracrine factors. Octreotide has... more Liver regeneration involves a significant variety of growth and paracrine factors. Octreotide has long been shown to inhibit liver regeneration, although the exact mechanism of its action remains unclear. This paper aims to examine the effect of long-term octreotide administration on the expression of the estrogen receptor type alpha (Era) as a potential novel pathway via which liver regeneration may be hindered. Sixty adult male Wistar rats were submitted to 70% (extensive) hepatectomy and subsequently randomized to receive either a subcutaneous injection of 50grams/kg body weight octreotide diluted in 1mL of 0.9% normal saline (SS group) or simply 1mL of 0.9% normal saline (NS group). Animals were followed up to 168 or 1440h (1 week and 1 month, respectively) post-hepatectomy and subsequently sacrificed. Removed livers were weighted, diluted in paraformaldehyde, embedded in paraffin wax, sliced at 5 micrometer intervals and prepared for the immunohistochemical detection of ERa. Th...
Collegium antropologicum, 2013
The aging process is a normal stage in development characterized by the gradual deterioration of ... more The aging process is a normal stage in development characterized by the gradual deterioration of all life functions. As far as reproduction is concerned, aging is characterized by a significant limitation of fertility in both sexes. This process is, at least partially, attributed to the action (or loss of action) of sex steroids, coinciding with low activity of the pituitary-gonad axis. From an anthropological point of view, the study of reproductive aging is a unique opportunity to investigate various environmental and endogenous factors influencing sexual behavior and, thus, playing a significant role in human biology. Various techniques are now widely available to allow the detailed examination of reproductive hazards using only minor samples of genetic material. These methods are highly sensitive and specific and allow the characterization of distortions at subcellular and even molecular level. This short review briefly summarizes the current understanding of reproductive aging,...
Reproductive biology and endocrinology : RB&E, 2006
Determining sexual fate is an integral part of reproduction, used as a means to enrich the genome... more Determining sexual fate is an integral part of reproduction, used as a means to enrich the genome. A variety of such regulatory mechanisms have been described so far and some of the more extensively studied ones are being discussed. For the insect order of Hymenoptera, the choice lies between uniparental haploid males and biparental diploid females, originating from unfertilized and fertilized eggs accordingly. This mechanism is also known as single-locus complementary sex determination (slCSD). On the other hand, for Dipterans and Drosophila melanogaster, sex is determined by the ratio of X chromosomes to autosomes and the sex switching gene, sxl. Another model organism whose sex depends on the X:A ratio, Caenorhabditis elegans, has furthermore to provide for the brief period of spermatogenesis in hermaphrodites (XX) without the benefit of the "male" genes of the sex determination pathway. Many reptiles have no discernible sex determining genes. Their sexual fate is deter...
Collegium antropologicum, 2006
The role of hormones in the determination of sexual characteristics has been known for several de... more The role of hormones in the determination of sexual characteristics has been known for several decades. It has been shown, for example, that several products, including sex steroids, may influence the body development pattern, metabolic pathways, fat and muscle distribution and vocal cord anatomy, thus producing an overall outcome consistent with a masculine or feminine phenotypic pattern. These qualities are usually described as secondary sexual traits, so as to be distinguished from primary sex traits, usually referring to the gonads and external genitalia. However, it must be noted that hormonal regulation may not explain the full range of the sexual phenotype, since the central nervous system retains a significant role in the establishment of sexual identity, thus giving rise to a higher sex determination stage exclusively described in humans, namely behavioral or psychological sex. Recently, it has been suggested that differences among the sexes are not limited to brain functio...
Collegium antropologicum, 2006
Sexual dimorphism, i.e. the distinct recognition of only two sexes per species, is the phenotypic... more Sexual dimorphism, i.e. the distinct recognition of only two sexes per species, is the phenotypic expression of a multi-stage procedure at chromosomal, gonadal, hormonal and behavioral level. Chromosomal--genetic sexual dimorphism refers to the presence of two identical (XX) or two different (XY) gonosomes in females and males, respectively. This is due to the distinct content of the X and Y-chromosomes in both genes and regulatory sequences, SRY being the key regulator Hormones (AMH, testosterone, Insl3) secreted by the foetal testis (gonadal sexual dimorphism), impede Müller duct development, masculinize Wolff duct derivatives and are involved in testicular descent (hormonal sexual dimorphism). Steroid hormone receptors detected in the nervous system, link androgens with behavioral sexual dimorphism. Furthermore, sex chromosome genes directly affect brain sexual dimorphism and this may precede gonadal differentiation.
Collegium antropologicum, 2006
The immense value of sex differentiation as a means of enriching and evolving the genome has been... more The immense value of sex differentiation as a means of enriching and evolving the genome has been proven by the vast variety of sex determining mechanisms to which organisms of all kinds resort. From single gene switching pathways found in lower level organisms to haplodiploid reproduction in hymenoptera, temperature-determined sex in reptiles and sex chromosomes in mammals and avians, nature and evolution have designated an impressive amount of effort to ensure that sex-specific variations remain under well-regulated control. Therefore enhancing our efforts to study some of the strategies recruited for the above may also lead to a better understanding of the inherent complexity of sexual dimorphism in general.
Collegium antropologicum, 2006
Dimorphism between testis and ovary in germ cells proliferative behavior, shows remarkable differ... more Dimorphism between testis and ovary in germ cells proliferative behavior, shows remarkable differences in foetal and neonatal period [14.5 days post conception (dpc)--7 days post partum (dpp)]. Immunostaining of the foetal testis, with the PCNA and Ki-67 antibodies [estimation of Labeling Index (LI)], reveals increasing germ cells population until birth. Afterwards, a sharp decline in the first 3 days of postnatal life and a transient increase, between 3 and 5 dpp, is observed. Then, the mitotic activity of germ cells ceases. In the foetal ovary, germ cells proliferation reaches a peak value before birth, decreasing thereafter Somatic (Sertoli or follicular) cells behave similarly in both sexes. Increased mitotic activity is observed throughout the examined period. Thus, the gonadal dimorphism in proliferative behavior, concerns only germ cell lineage and is established during the foetal and neonatal period.
Tissue and Cell, 2008
The aim of the current paper is to evaluate the correlation of germ and follicular cells kinetics... more The aim of the current paper is to evaluate the correlation of germ and follicular cells kinetics during ovarian morphogenesis. Thus, immunohistochemical detection of PCNA and Ki-67 proteins has been examined using PC10 (Dako) and NCL-Ki-67 (Novocastra) antibodies in the developing ovaries of Wistar rat embryos and neonates [14.5, 18.5, 20.5 days post-coitum (dpc), birth (day 0), 1, 3, 5, 7 day post-partum (dpp)]. Estimation of reactive/total cell ratio, per cell type (germ and follicular cells) and visual field was achieved using the Image Pro Plus Software. The statistical interpretation of the results has shown that, before birth, using the PCNA antibody, the percentage of labeled/total germ cells (labeling index, LI) increases from 71.19% at 14.5 dpc to 75.66% at 18.5 dpc. It then decreases to 73.26% at 20.5 dpc. At birth, the labeling index drops significantly (28.57%). Immediately after birth, the percentage of labeled/total germ cells increases, reaching 43.58% at 1 dpp. Subsequently, a further decrease in the percentage of reactive cells is observed resulting to a maximum drop of the LI at 7 dpp (18.41%). Using the Ki-67 antibody, the percentage of labeled/total germ cells is generally lower although the fluctuation is similar with that observed using the first marker of cell proliferation. Using the PCNA antibody, the LI of follicular cells in the developing ovary, increases from 0.70% (at 14.5 dpc) to 28.94% (at 18.5 dpc) and then drops to 18.03% (at 20.5 dpc). At birth, the percentage of reactive follicular cells, reaches 27.66% and remains high thereafter. Similar results are obtained using the Ki-67 antibody. In conclusion, follicular cell reaction ratio, using both antibodies (PCNA and Ki-67), increases continuously throughout the examined period with a maximum value at 7 dpp, suggesting a kinetics profile similar to that observed for Sertoli cells in the testis. In all age groups, PCNA labeling is more intense than Ki-67, a result that may be attributed to selective staining at different periods of the cell cycle.
Reproductive Toxicology, 2012
Reactive oxygen species (ROS) are active byproducts of aerobic metabolism. Although they are cons... more Reactive oxygen species (ROS) are active byproducts of aerobic metabolism. Although they are constantly produced during normal cellular activities in the mitochondria, their action is counteracted by inherent antioxidant systems. This equilibrium is distorted in the case of acute or chronic inflammation, which results in increased ROS production and, ultimately, oxidative stress. In sperm, ROS are produced by both spermatozoa and circulating leucocytes and may be part of normal adaptive reactions, such as the capacitation process. However, a number of external toxicants may also contribute to ROS production in the testis and epididymis, leading to a decrease in sperm viability and motility and, therefore, an increased onset of the male factor of infertility. Such pro-oxidative conditions include, among others, exposure to radiation, extreme temperature, certain drugs, toxins, heavy metals, smoking and biological hazards. The current review paper summarizes the available evidence incriminating ROS and oxidative stress as the underlying pathophysiological mechanism leading to the onset of reproductive toxicity in each of these settings.
Reproductive Toxicology, 2009
The aging process is a complex biological phenomenon that can be attributed to several mechanisms... more The aging process is a complex biological phenomenon that can be attributed to several mechanisms. ROS (reactive oxygen species) activity is widely considered one of them, as it is associated with extensive damage in a variety of cells. For example, the gradual decrease in fertility often accompanying aging males can be traced back to oxidative stress, since ROS are released throughout life from the mitochondrial respiratory chain. Cumulative intracellular damage as a result of the increased ROS concentration affects all tissues that perform aerobic metabolism and, owing to blood circulation, anaerobic tissues as well. Naturally, other mechanisms such as cell inflammation and lack or incapacity of antioxidant enzymes also contribute to the variety of systematic distortions that characterize aging. Finally, the particularly elevated number of adult men that show, among others, a gradual deterioration in reproductive functions suggests a central role of ROS generation in senescence in general and male aging, in particular.
Reproductive Biology and Endocrinology, 2008
Chromosomal sex determination is a widely distributed strategy in nature. In the most classic sce... more Chromosomal sex determination is a widely distributed strategy in nature. In the most classic scenario, one sex is characterized by a homologue pair of sex chromosomes, while the other includes two morphologically and functionally distinct gonosomes. In mammalian diploid cells, the female is characterized by the presence of two identical X chromosomes, while the male features an XY pair, with the Y bearing the major genetic determinant of sex, i.e. the SRY gene. In other species, such as the fruitfly, sex is determined by the ratio of autosomes to X chromosomes. Regardless of the exact mechanism, however, all these animals would exhibit a sex-specific gene expression inequality, due to the different number of X chromosomes, a phenomenon inhibited by a series of genetic and epigenetic regulatory events described as "dosage compensation". Since adequate available data is currently restricted to worms, flies and mammals, while for other groups of animals, such as reptiles, fish and birds it is very limited, it is not yet clear whether this is an evolutionary conserved mechanism. However certain striking similarities have already been observed among evolutionary distant species, such as Drosophila melanogaster and Mus musculus. These mainly refer to a) the need for a counting mechanism, to determine the chromosomal content of the cell, i.e. the ratio of autosomes to gonosomes (a process well understood in flies, but still hypothesized in mammals), b) the implication of non-translated, sex-specific, regulatory RNAs (roX and Xist, respectively) as key elements in this process and the location of similar mediators in the Z chromosome of chicken c) the inclusion of a chromatin modification epigenetic final step, which ensures that gene expression remains stably regulated throughout the affected area of the gonosome. This review summarizes these points and proposes a possible role for comparative genetics, as they seem to constitute proof of maintained cell economy (by using the same basic regulatory elements in various different scenarios) throughout numerous centuries of evolutionary history.
Journal of Men's Health, 2009
Journal of Men's Health, 2009
Journal of Assisted Reproduction and Genetics, 2009
Anthropology Today, 2004
The International Congress of the Hellenic Anthropological Association (HAA), Athens, 21‐23 Novem... more The International Congress of the Hellenic Anthropological Association (HAA), Athens, 21‐23 November 2003
Acta Histochemica, 2008
Sertoli cell population kinetics, as evidenced by semi-quantitative immunolabeling for proliferat... more Sertoli cell population kinetics, as evidenced by semi-quantitative immunolabeling for proliferating cell nuclear antigen (PCNA) and Ki-67, in developing Wistar rat male gonads of embryos and neonates [14.5 days post conception (dpc)-7 days post partum (dpp)], was investigated. Throughout the examined period a gradual increase of immunolabeled Sertoli cell number, associated with intense mitotic activity, was observed. PCNA labeling index of Sertoli cells increased from 66.67 (at 14.5 dpc) to 89.74 (at 18.5 dpc) and then dropped to 75.24 (at 20.5 dpc). At birth, the percentage of PCNA immunoreactive Sertoli cells reached 98.70% and remained high thereafter, attaining a peak value of 99.90% at 7 dpp. The percentage of Ki-67 immunoreactive Sertoli cells in the fetal testis increased from E14.5 (43.95%) to E20.5 (77.40%). The proliferation rate did not alter considerably in the neonatal testis until 5 dpp. At this point, a significant increase of the Ki-67 labeling index was observed and a peak value of 95.76% was reached at 7 dpp. The pattern of Sertoli cell proliferation with age and the establishment of the final Sertoli cell number in vivo established in the present study was compared to the results from earlier investigations reported in the literature and the observed fluctuation of dividing cell numbers, associated with immunolabeling results throughout the examined period, complements and extends existing data. An appraisal of the timing of Sertoli cell proliferation in other species, namely mouse and man, is presented. The current investigation may be useful in evaluating the potential influence of
Copyright The © successful 2008 AHCtreatment of breast cancer is dependent upon a number of compl... more Copyright The © successful 2008 AHCtreatment of breast cancer is dependent upon a number of complex factors. Her-2/neu gene amplification is known to be one of the most common genetic alterations associated with breast cancer and its accurate determination has become necessary for the selection of patients for trastuzumab therapy. The aim of this study was to prove the consistency of chromogenic in situ hybridisation (CISH) technique after analyzing the overexpression of the Her-2/neu proto-oncogene in 100 invasive breast carcinomas and by comparing CISH results with immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH). Moreover, it was done to evaluate the possible correlation of estrogen (ERs) and progesterone receptors (PRs), the proliferation marker Ki67 and the tumour suppressor gene p53 with HER-2/neu status of these breast carcinomas. Of the 100 breast carcinomas that were analysed, 22 cases showed HER-2/neu amplification, 66 cases showed no amplification,...
Collegium antropologicum, 2015
Cardiovascular disease shows a distinct difference in incidence rates between men and women, a fa... more Cardiovascular disease shows a distinct difference in incidence rates between men and women, a fact that has been known for many years. While initial theories supported that this could be attributed to the protective effect of estrogens in women, attempts to correlate endogenous estrogen levels with cardiovascular risk factors and the progression of atherosclerosis-related indexes indicate otherwise. Similarly, endogenous androgen levels seem to correlate with opposite effects in males and females, whereas exogenous treatment with either androgens or estrogens fails to correspond to scientific expectations entirely. A brief discussion of the merits and pitfalls of placing either estrogens or androgens alone at the root of the problem shows that current understanding is inadequate concerning this major anthropological issue, as it refers to the primary global mortality and morbidity cause.
Collegium antropologicum, 2013
Sexual dimorphism is a characteristic of a large number of species, ranging from lower invertebra... more Sexual dimorphism is a characteristic of a large number of species, ranging from lower invertebrates to mammals and, last but not least, humans. Recognition of the various factors regulating sexual dimorphism initial establishment (i.e. sex determination and differentiation) and subsequent life-long adaptation to distinct functional and behavioural patterns has remained a hot topic for several decades. As our understanding of the various molecular pathways involved in this process increases, the significant role of sex steroids becomes more evident. At the same time, the recognition of new sites of steroid production (e.g. parts of the brain) and aromatization, as well as new target cells (owing to the proposed presence of additional receptors to those classically considered as primary steroid receptors) has lead to the need to revisit their spectrum of actions within a novel, multifactorial context. Thus, anthropology and medicine are presented with the challenge to unravel a major...
Collegium antropologicum, 2013
Anthropology has always been particularly interested in the origin of human life and the developm... more Anthropology has always been particularly interested in the origin of human life and the development towards adulthood. Although originally working with skeletal measurements and bio-morphological markers in modern populations, it has now entered the growing field of applied molecular biology. This relatively recent advance allows the detailed study of major events in human development and senescence. For instance, sperm DNA integrity and chromatin re-organization are crucial factors for fertilization and embryo development. Clinical researchers have developed improved methods for the evaluation of DNA integrity and protaminosis in sperm nuclei, such as the TUNEL and the CMA3 assays. DNA damage in spermatozoal nuclei is detected using the TUNEL assay which depends on the specific enzymatic reaction of TdT with the end strand breaks of DNA. Protaminosis in spermatozoal nucleus is evaluated using CMA3 assay, which is based on the in situ competition between CMA3 and protamines. Such m...
Hellenic journal of nuclear medicine
Liver regeneration involves a significant variety of growth and paracrine factors. Octreotide has... more Liver regeneration involves a significant variety of growth and paracrine factors. Octreotide has long been shown to inhibit liver regeneration, although the exact mechanism of its action remains unclear. This paper aims to examine the effect of long-term octreotide administration on the expression of the estrogen receptor type alpha (Era) as a potential novel pathway via which liver regeneration may be hindered. Sixty adult male Wistar rats were submitted to 70% (extensive) hepatectomy and subsequently randomized to receive either a subcutaneous injection of 50grams/kg body weight octreotide diluted in 1mL of 0.9% normal saline (SS group) or simply 1mL of 0.9% normal saline (NS group). Animals were followed up to 168 or 1440h (1 week and 1 month, respectively) post-hepatectomy and subsequently sacrificed. Removed livers were weighted, diluted in paraformaldehyde, embedded in paraffin wax, sliced at 5 micrometer intervals and prepared for the immunohistochemical detection of ERa. Th...
Collegium antropologicum, 2013
The aging process is a normal stage in development characterized by the gradual deterioration of ... more The aging process is a normal stage in development characterized by the gradual deterioration of all life functions. As far as reproduction is concerned, aging is characterized by a significant limitation of fertility in both sexes. This process is, at least partially, attributed to the action (or loss of action) of sex steroids, coinciding with low activity of the pituitary-gonad axis. From an anthropological point of view, the study of reproductive aging is a unique opportunity to investigate various environmental and endogenous factors influencing sexual behavior and, thus, playing a significant role in human biology. Various techniques are now widely available to allow the detailed examination of reproductive hazards using only minor samples of genetic material. These methods are highly sensitive and specific and allow the characterization of distortions at subcellular and even molecular level. This short review briefly summarizes the current understanding of reproductive aging,...
Reproductive biology and endocrinology : RB&E, 2006
Determining sexual fate is an integral part of reproduction, used as a means to enrich the genome... more Determining sexual fate is an integral part of reproduction, used as a means to enrich the genome. A variety of such regulatory mechanisms have been described so far and some of the more extensively studied ones are being discussed. For the insect order of Hymenoptera, the choice lies between uniparental haploid males and biparental diploid females, originating from unfertilized and fertilized eggs accordingly. This mechanism is also known as single-locus complementary sex determination (slCSD). On the other hand, for Dipterans and Drosophila melanogaster, sex is determined by the ratio of X chromosomes to autosomes and the sex switching gene, sxl. Another model organism whose sex depends on the X:A ratio, Caenorhabditis elegans, has furthermore to provide for the brief period of spermatogenesis in hermaphrodites (XX) without the benefit of the "male" genes of the sex determination pathway. Many reptiles have no discernible sex determining genes. Their sexual fate is deter...
Collegium antropologicum, 2006
The role of hormones in the determination of sexual characteristics has been known for several de... more The role of hormones in the determination of sexual characteristics has been known for several decades. It has been shown, for example, that several products, including sex steroids, may influence the body development pattern, metabolic pathways, fat and muscle distribution and vocal cord anatomy, thus producing an overall outcome consistent with a masculine or feminine phenotypic pattern. These qualities are usually described as secondary sexual traits, so as to be distinguished from primary sex traits, usually referring to the gonads and external genitalia. However, it must be noted that hormonal regulation may not explain the full range of the sexual phenotype, since the central nervous system retains a significant role in the establishment of sexual identity, thus giving rise to a higher sex determination stage exclusively described in humans, namely behavioral or psychological sex. Recently, it has been suggested that differences among the sexes are not limited to brain functio...
Collegium antropologicum, 2006
Sexual dimorphism, i.e. the distinct recognition of only two sexes per species, is the phenotypic... more Sexual dimorphism, i.e. the distinct recognition of only two sexes per species, is the phenotypic expression of a multi-stage procedure at chromosomal, gonadal, hormonal and behavioral level. Chromosomal--genetic sexual dimorphism refers to the presence of two identical (XX) or two different (XY) gonosomes in females and males, respectively. This is due to the distinct content of the X and Y-chromosomes in both genes and regulatory sequences, SRY being the key regulator Hormones (AMH, testosterone, Insl3) secreted by the foetal testis (gonadal sexual dimorphism), impede Müller duct development, masculinize Wolff duct derivatives and are involved in testicular descent (hormonal sexual dimorphism). Steroid hormone receptors detected in the nervous system, link androgens with behavioral sexual dimorphism. Furthermore, sex chromosome genes directly affect brain sexual dimorphism and this may precede gonadal differentiation.
Collegium antropologicum, 2006
The immense value of sex differentiation as a means of enriching and evolving the genome has been... more The immense value of sex differentiation as a means of enriching and evolving the genome has been proven by the vast variety of sex determining mechanisms to which organisms of all kinds resort. From single gene switching pathways found in lower level organisms to haplodiploid reproduction in hymenoptera, temperature-determined sex in reptiles and sex chromosomes in mammals and avians, nature and evolution have designated an impressive amount of effort to ensure that sex-specific variations remain under well-regulated control. Therefore enhancing our efforts to study some of the strategies recruited for the above may also lead to a better understanding of the inherent complexity of sexual dimorphism in general.
Collegium antropologicum, 2006
Dimorphism between testis and ovary in germ cells proliferative behavior, shows remarkable differ... more Dimorphism between testis and ovary in germ cells proliferative behavior, shows remarkable differences in foetal and neonatal period [14.5 days post conception (dpc)--7 days post partum (dpp)]. Immunostaining of the foetal testis, with the PCNA and Ki-67 antibodies [estimation of Labeling Index (LI)], reveals increasing germ cells population until birth. Afterwards, a sharp decline in the first 3 days of postnatal life and a transient increase, between 3 and 5 dpp, is observed. Then, the mitotic activity of germ cells ceases. In the foetal ovary, germ cells proliferation reaches a peak value before birth, decreasing thereafter Somatic (Sertoli or follicular) cells behave similarly in both sexes. Increased mitotic activity is observed throughout the examined period. Thus, the gonadal dimorphism in proliferative behavior, concerns only germ cell lineage and is established during the foetal and neonatal period.
Tissue and Cell, 2008
The aim of the current paper is to evaluate the correlation of germ and follicular cells kinetics... more The aim of the current paper is to evaluate the correlation of germ and follicular cells kinetics during ovarian morphogenesis. Thus, immunohistochemical detection of PCNA and Ki-67 proteins has been examined using PC10 (Dako) and NCL-Ki-67 (Novocastra) antibodies in the developing ovaries of Wistar rat embryos and neonates [14.5, 18.5, 20.5 days post-coitum (dpc), birth (day 0), 1, 3, 5, 7 day post-partum (dpp)]. Estimation of reactive/total cell ratio, per cell type (germ and follicular cells) and visual field was achieved using the Image Pro Plus Software. The statistical interpretation of the results has shown that, before birth, using the PCNA antibody, the percentage of labeled/total germ cells (labeling index, LI) increases from 71.19% at 14.5 dpc to 75.66% at 18.5 dpc. It then decreases to 73.26% at 20.5 dpc. At birth, the labeling index drops significantly (28.57%). Immediately after birth, the percentage of labeled/total germ cells increases, reaching 43.58% at 1 dpp. Subsequently, a further decrease in the percentage of reactive cells is observed resulting to a maximum drop of the LI at 7 dpp (18.41%). Using the Ki-67 antibody, the percentage of labeled/total germ cells is generally lower although the fluctuation is similar with that observed using the first marker of cell proliferation. Using the PCNA antibody, the LI of follicular cells in the developing ovary, increases from 0.70% (at 14.5 dpc) to 28.94% (at 18.5 dpc) and then drops to 18.03% (at 20.5 dpc). At birth, the percentage of reactive follicular cells, reaches 27.66% and remains high thereafter. Similar results are obtained using the Ki-67 antibody. In conclusion, follicular cell reaction ratio, using both antibodies (PCNA and Ki-67), increases continuously throughout the examined period with a maximum value at 7 dpp, suggesting a kinetics profile similar to that observed for Sertoli cells in the testis. In all age groups, PCNA labeling is more intense than Ki-67, a result that may be attributed to selective staining at different periods of the cell cycle.
Reproductive Toxicology, 2012
Reactive oxygen species (ROS) are active byproducts of aerobic metabolism. Although they are cons... more Reactive oxygen species (ROS) are active byproducts of aerobic metabolism. Although they are constantly produced during normal cellular activities in the mitochondria, their action is counteracted by inherent antioxidant systems. This equilibrium is distorted in the case of acute or chronic inflammation, which results in increased ROS production and, ultimately, oxidative stress. In sperm, ROS are produced by both spermatozoa and circulating leucocytes and may be part of normal adaptive reactions, such as the capacitation process. However, a number of external toxicants may also contribute to ROS production in the testis and epididymis, leading to a decrease in sperm viability and motility and, therefore, an increased onset of the male factor of infertility. Such pro-oxidative conditions include, among others, exposure to radiation, extreme temperature, certain drugs, toxins, heavy metals, smoking and biological hazards. The current review paper summarizes the available evidence incriminating ROS and oxidative stress as the underlying pathophysiological mechanism leading to the onset of reproductive toxicity in each of these settings.
Reproductive Toxicology, 2009
The aging process is a complex biological phenomenon that can be attributed to several mechanisms... more The aging process is a complex biological phenomenon that can be attributed to several mechanisms. ROS (reactive oxygen species) activity is widely considered one of them, as it is associated with extensive damage in a variety of cells. For example, the gradual decrease in fertility often accompanying aging males can be traced back to oxidative stress, since ROS are released throughout life from the mitochondrial respiratory chain. Cumulative intracellular damage as a result of the increased ROS concentration affects all tissues that perform aerobic metabolism and, owing to blood circulation, anaerobic tissues as well. Naturally, other mechanisms such as cell inflammation and lack or incapacity of antioxidant enzymes also contribute to the variety of systematic distortions that characterize aging. Finally, the particularly elevated number of adult men that show, among others, a gradual deterioration in reproductive functions suggests a central role of ROS generation in senescence in general and male aging, in particular.
Reproductive Biology and Endocrinology, 2008
Chromosomal sex determination is a widely distributed strategy in nature. In the most classic sce... more Chromosomal sex determination is a widely distributed strategy in nature. In the most classic scenario, one sex is characterized by a homologue pair of sex chromosomes, while the other includes two morphologically and functionally distinct gonosomes. In mammalian diploid cells, the female is characterized by the presence of two identical X chromosomes, while the male features an XY pair, with the Y bearing the major genetic determinant of sex, i.e. the SRY gene. In other species, such as the fruitfly, sex is determined by the ratio of autosomes to X chromosomes. Regardless of the exact mechanism, however, all these animals would exhibit a sex-specific gene expression inequality, due to the different number of X chromosomes, a phenomenon inhibited by a series of genetic and epigenetic regulatory events described as "dosage compensation". Since adequate available data is currently restricted to worms, flies and mammals, while for other groups of animals, such as reptiles, fish and birds it is very limited, it is not yet clear whether this is an evolutionary conserved mechanism. However certain striking similarities have already been observed among evolutionary distant species, such as Drosophila melanogaster and Mus musculus. These mainly refer to a) the need for a counting mechanism, to determine the chromosomal content of the cell, i.e. the ratio of autosomes to gonosomes (a process well understood in flies, but still hypothesized in mammals), b) the implication of non-translated, sex-specific, regulatory RNAs (roX and Xist, respectively) as key elements in this process and the location of similar mediators in the Z chromosome of chicken c) the inclusion of a chromatin modification epigenetic final step, which ensures that gene expression remains stably regulated throughout the affected area of the gonosome. This review summarizes these points and proposes a possible role for comparative genetics, as they seem to constitute proof of maintained cell economy (by using the same basic regulatory elements in various different scenarios) throughout numerous centuries of evolutionary history.
Journal of Men's Health, 2009
Journal of Men's Health, 2009
Journal of Assisted Reproduction and Genetics, 2009
Anthropology Today, 2004
The International Congress of the Hellenic Anthropological Association (HAA), Athens, 21‐23 Novem... more The International Congress of the Hellenic Anthropological Association (HAA), Athens, 21‐23 November 2003
Acta Histochemica, 2008
Sertoli cell population kinetics, as evidenced by semi-quantitative immunolabeling for proliferat... more Sertoli cell population kinetics, as evidenced by semi-quantitative immunolabeling for proliferating cell nuclear antigen (PCNA) and Ki-67, in developing Wistar rat male gonads of embryos and neonates [14.5 days post conception (dpc)-7 days post partum (dpp)], was investigated. Throughout the examined period a gradual increase of immunolabeled Sertoli cell number, associated with intense mitotic activity, was observed. PCNA labeling index of Sertoli cells increased from 66.67 (at 14.5 dpc) to 89.74 (at 18.5 dpc) and then dropped to 75.24 (at 20.5 dpc). At birth, the percentage of PCNA immunoreactive Sertoli cells reached 98.70% and remained high thereafter, attaining a peak value of 99.90% at 7 dpp. The percentage of Ki-67 immunoreactive Sertoli cells in the fetal testis increased from E14.5 (43.95%) to E20.5 (77.40%). The proliferation rate did not alter considerably in the neonatal testis until 5 dpp. At this point, a significant increase of the Ki-67 labeling index was observed and a peak value of 95.76% was reached at 7 dpp. The pattern of Sertoli cell proliferation with age and the establishment of the final Sertoli cell number in vivo established in the present study was compared to the results from earlier investigations reported in the literature and the observed fluctuation of dividing cell numbers, associated with immunolabeling results throughout the examined period, complements and extends existing data. An appraisal of the timing of Sertoli cell proliferation in other species, namely mouse and man, is presented. The current investigation may be useful in evaluating the potential influence of
Copyright The © successful 2008 AHCtreatment of breast cancer is dependent upon a number of compl... more Copyright The © successful 2008 AHCtreatment of breast cancer is dependent upon a number of complex factors. Her-2/neu gene amplification is known to be one of the most common genetic alterations associated with breast cancer and its accurate determination has become necessary for the selection of patients for trastuzumab therapy. The aim of this study was to prove the consistency of chromogenic in situ hybridisation (CISH) technique after analyzing the overexpression of the Her-2/neu proto-oncogene in 100 invasive breast carcinomas and by comparing CISH results with immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH). Moreover, it was done to evaluate the possible correlation of estrogen (ERs) and progesterone receptors (PRs), the proliferation marker Ki67 and the tumour suppressor gene p53 with HER-2/neu status of these breast carcinomas. Of the 100 breast carcinomas that were analysed, 22 cases showed HER-2/neu amplification, 66 cases showed no amplification,...