Biomedical subjects

Roxani Angelopoulou

Publications and source records attributed to Roxani Angelopoulou.

7 recordsLinked to original sources

PubMed2006

Molecular patterns of sex determination in the animal kingdom: a comparative study of the biology of reproduction.

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 determined by the temperature of the environment during the thermosensitive period (TSP) of incubation, which regulates aromatase activity. Variable patterns of sex determination apply in fish and amphibians. In birds, while sex chromosomes do exist, females are the heterogametic (ZW) and males the homogametic sex (ZZ). However, we have yet to decipher which of the two (Z or W) is responsible for the choice between males and females. In mammals, sex determination is based on the presence of two identical (XX) or distinct (XY) gonosomes. This is believed to be the result of a lengthy evolutionary process, emerging from a common ancestral autosomal pair. Indeed, X and Y present different levels of homology in various mammals, supporting the argument of a gradual structural differentiation starting around the SRY region. The latter initiates a gene cascade that results in the formation of a male. Regulation of sex steroid production is also a major result of these genetic interactions. Similar observations have been described not only in mammals, but also in other vertebrates, emphasizing the need for further study of both normal hormonal regulators of sexual phenotype and patterns of epigenetic/environmental disruption.

Amphibians↗

PubMed2006

The effects of age on the incidence of aneuploidy rates in spermatozoa of oligoasthenozoospermic patients and its relationship with ICSI outcome.

The development of intracytoplasmic sperm injection (ICSI) for treatment of infertility as a result of severe male factor has improved the chances of achieving pregnancy in many infertile couples. However, concerns have been raised regarding the safety of this technique, because natural sperm selection is bypassed. In the present study, 25 oligoasthenozoospermic patients who were divided into two groups according to age: group A, 20-34 (n = 10) and group B, 35-50 (n = 15), were included. Pooling the data of the three semen parameters that were tested (volume, concentration and progressive motility) no statistically significant difference between the two age groups was found. A total of 50 883 decondensed spermatozoa was analysed using the dual and triple colour fluorescence in situ hybridization to estimate the rates of aneuploidy for chromosomes 13, 18, 21, X and Y in the two age groups. There was a significantly higher incidence of disomy for chromosome 21 compared to the other autosomes (chromosomes 13 and 18) in both age groups. The disomy rate of XY was significantly higher in the younger subject group (0.1%) compared to the older group (0.05%, p < 0.05). Statistically significant differences in the mean number of clinical pregnancies and abortions were not observed between the two age groups. The aneuploidy rates for all the analysed chromosomes did not differ significantly, both between and within the two age groups, and as a result there seems to be no effect of male age on chromosome numbers in the spermatozoa and on the ICSI outcome.

Adult↗

PubMed2006

Gonadal cell proliferation dimorphism.

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.

Animals↗

PubMed2006

Sex determinants in the genome--lessons from the animal kingdom.

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.

Animals↗

PubMed2006

Establishing sexual dimorphism in humans.

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.

Animals↗

PubMed2006

Hormonal and meta-hormonal determinants of sexual dimorphism.

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 function but they may also refer to anatomical differences and different biochemical profiles, including a distinct pattern of AR and ER distribution. This new aspect of sexual dimorphism suggests a whole system of meta-hormonal regulation, recently described as the sexual brain model. The role of local androgen and/or estrogen concentrations in the initial establishment of brain sexual dimorphism is still under evaluation, since the first results are relatively inconclusive and no direct cause and effect relationship has been proven so far. On the other hand, sex hormones have recently been found to participate in processes well beyond their initially suggested spectrum of action. For instance, ER interacts with EGFR in a number of ways, affecting development of a number of epithelial structures. Estrogen receptors have also been detected in a number of non-classic targets of steroids, such as the brain and the lungs. This observation may imply that sexual dimorphism goes a lot deeper than previously estimated, affecting virtually every organic system, suggesting, in essence, the existence of two different functional models for the whole human body, formulated and conserved throughout the evolutionary progress.

Brain↗

PubMed2005

Using BAC clones to characterize unbalanced chromosome abnormalities in interphase cells.

Carriers of balanced translocations usually carry alterations in gene sequences, which lead to dysfunction during early and late embryogenesis. Related spatial rearrangement causes either cumulative delay in cell cycles and/or anomalies in transcription and translation. This has also an important impact at the time of genomic activation, the longest cell cycle of preimplantation development. Carrier patients may be affected either with primary infertility or by repeated miscarriages [Hum. Reprod. 12 (1997) 2019.]. Assuming that a fraction of the germ cells is karyotypically normal, these patients would greatly benefit from efficient procedures for generation and use of breakpoint-specific DNA hybridisation probes in preconception and preimplantation genetic diagnosis (PGD) after polar body or blastomere biopsy of the embryos. The objective of this research was to design an approach of patient-specific probes for preimplantation diagnosis of chromosome translocations and which could be used eventually to select chromosomally normal embryos from balanced or unbalanced interphase cells prior to their transfer to the mother's womb. This approach was used for a couple, where the female partner was a carrier of a balanced translocation 46,XX,t(4;12)(p16.1;q24.31). First, BAC/PAC clones were chosen from specific chromosome bands from the genome sequence that hybridise adjacent to the chromosomal breakpoints or span them. Then, the probes and hybridisation conditions were optimised using unrelated normal amniocytes, lymphoblastoid cells and lymphocytes from the carrier to increase hybridisation signal intensity and decrease background. Finally, the probes were tested on target cells before they were used for mimicking preconception or preimplantation genetic diagnosis. Three slides were analysed blindly from a normal karyotype, an unbalanced and a balanced translocation. A total of 78 cells were analysed of which in the slide A 19/22 (86%) were found to be unbalanced, in slide B 25/31 (81%) were normal and in slide C 21/25 (84%) were balanced. Thus, it was demonstrated that cells with known structural abnormalities could be detected, based on hybridisation of breakpoint spanning bacterial artificial chromosome (BAC) DNA probes in interphase cells.

Adult↗