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Objective To determine chromosome and gene alterations in ectopic endometrial (EM) tissue which may be implicated in the clinical course or the progression of endometriosis and to review the literature concerning the cytogenetic findings of women with endometriosis. Study design 15 women who underwent laparoscopic endometriosis surgery at the Athens Genesis Clinic were enrolled in the study. Ectopic endometrial tissue was surgically removed and further analyzed by conventional and molecular cytogenetic techniques. Fluoresent in situ hibridization (FISH) with probes for p53, ATM, MYC, MLL1 and IGH genes, the centromeres of chromosomes 7 and 8 and 7q22/7q31 chromosomal regions was carried out. Results Karyotypic analysis revealed no clonal chromosomal abnormalities. However, an increased frequency of polyploidy (55.6%) and sporadic chromosomal abnormalities (40.0%) concerning chromosomes 9, 11, 17 and X were noticed involving mainly deletions, trisomies or monosomies. FISH analysis showed IGH gene rearrangements in 54% of the EM cases and MLL gene rearrangements in 73% of the examined samples. Normal hybridization patterns were observed for p53, ATM and MYC. The increased frequency of polyploidy shown by conventional karyotyping was also confirmed by FISH. Conclusion Polyploidy, sporadic chromosomal abnormalities, as well as IGH and MLL gene rearrangements, may provoke genetic instability and play a potential role in the development of endometriosis. IGH and MLL gene rearrangements indicate a genetic relation between endometriosis and carcinogenesis. Confirmation of the above gene rearrangements in a large series of women may allow the determination of their possible involvement in the pathogenesis of this complex disease and their possible contribution in the early identification of women in danger for malignant transformation.

Chromosomal abnormalities are often detected in women with reproductive problems. This study aimed to investigate the presence and type of chromosomal aberrations in peripheral blood of women undergoing in vitro fertilization (IVF) and their possible association with advanced maternal age (AMA). A total of 1,837 women undergoing IVF between 2016 and 2019 were enrolled in the study. Women were further divided in AMA (≥35 years) and younger women (p < 0.05). Women of AMA exhibited X chromosome mosaicism with a frequency of 16.1%, and mosaic karyotypes with 2 and 3 aneuploid cell lines were more frequently detected. X chromosome mosaicism is the most common karyotypic aberration in women undergoing IVF and has 6-fold increased incidence in AMA women compared to younger ones. The present study verifies previous observations that low-level peripheral blood X chromosome mosaicism and the number of aneuploid cell lines observed in women of AMA could be an indication of aneuploidy and poor quality of oocytes contributing to infertility.

The main aim of the present systematic review was to summarize the most frequently used telomerase regulators with an impact on aging and cancer that are referred to in in vitro and in vivo studies. For this purpose, a systematic review of the available literature on telomerase regulators referred to in articles from PubMed and Scopus libraries published from 2002 to 2021 and in accordance with PRISMA 2020 criteria, was conducted. Articles were included if they met the following criteria: They referred to telomerase modulators in aging and in cancer and were in vitro and/or in vivo studies, while studies that did not provide sufficient data or studies not written in English were excluded. In the present systematic review, 54 publications were included, of which 29 were full-text published studies, 11 were full-text reviews, 10 structure-based design studies and 4 abstracts are reported in this review. Telomerase regulators were then categorized as synthetic direct telomerase inhibitors, synthetic indirect telomerase inhibitors, synthetic telomerase activators, natural direct telomerase activators, natural telomerase inhibitors and natural indirect telomerase activators, according to their origin and their activity. On the whole, as demonstrated herein, telomerase regulators appear to be promising treatment agents in various age-related diseases. However, further in vivo and in vitro studies need to be performed in order to clarify the potentiality of telomerase as a therapeutic target. Title in WoS: tau elomerase inhibitors and activators in aging and cancer: A systematic review

Background/aim To determine the incidence of X chromosome mosaicism in women undergoing in vitro fertilization (IVF) treatment and present preimplantation genetic testing for aneuploidy (PGT-A) outcome of this group. Patients and methods A total of 1,058 women undergoing IVF and 154 women with no fertility problems were enrolled in the study. Karyotyping from peripheral blood lymphocytes was performed by conventional cytogenetics. Twenty-nine women with X mosaicism underwent PGT-A by array-comparative genomic hybridization from embryos at the blastocyst stage. Results and conclusion Out of 1,058 women undergoing IVF, 166 (15.7%) had an abnormal karyotype. The most common finding (14.6%) was X chromosome mosaicism. Its frequency was higher in women >35 years old and reached 46.1% in those >45 years of age. PGT-A results of 130 blastocysts tested showed that 29/117 (24.8%) were euploid; 17/29 (60%) were transferred and 10/17 (70%) were successfully implanted, indicating that PGT-A may be an option for women with low-level X chromosome mosaicism undergoing IVF in order to improve the likelihood of a successful pregnancy outcome.

To describe a novel unbalanced X;21 translocation resulting in a derivative pseudodicentric chromosome X;21 lacking the critical region for ovarian development and function, in a 16-year-old girl referred for cytogenetic analysis due to primary amenorrhea and Turner-like features.Cytogenetic analysis of the proband and her parents was performed on peripheral blood lymphocytes by GTG banding. Molecular cytogenetic FISH analysis was performed on metaphase preparations, using X chromosome centromeric probe and telomeric and pancentromeric peptide nucleic acid (PNA) analog probes. The HUMARA assay as well as methylation studies for PCSK1N and FMR-1 loci were performed.Cytogenetic analysis revealed aPrimary amenorrhea and other Turner-like characteristics of the proband are apparently due to the loss of the Xq22.2→Xqter critical region which contains critical genes for the ovarian development and function. The chromosome X segment of the derivative pseudodicentric chromosome is selectively inactivated, but inactivation does not seem to spread onto the translocated chromosome 21, accounting probably for the lack of severe clinical consequences which would result from monosomy 21.

Background: In view of the current interest in exploring the clinical use of mesenchymal stem cells (MSCs) from different sources, we performed a side-by-side comparison of the biological properties of MSCs isolated from the Wharton's jelly (WJ), the most abundant MSC source in umbilical cord, with bone marrow (BM)-MSCs, the most extensively studied MSC population.Methods: MSCs were isolated and expanded from BM aspirates of hematologically healthy donors (n = 18) and from the WJ of full-term neonates (n = 18). We evaluated, in parallel experiments, the MSC immunophenotypic, survival and senescence characteristics as well as their proliferative potential and cell cycle distribution. We also assessed the expression of genes associated with the WNT- and cell cycle-signaling pathway and we performed karyotypic analysis through passages to evaluate the MSC genomic stability. The hematopoiesis-supporting capacity of MSCs from both sources was investigated by evaluating the clonogenic cells in the non-adherent fraction of MSC co-cultures with BM or umbilical cord blood-derived CD34+ cells and by measuring the hematopoietic cytokines levels in MSC culture supernatants. Finally, we evaluated the ability of MSCs to differentiate into adipocytes and osteocytes and the effect of the WNT-associated molecules WISP-1 and sFRP4 on the differentiation potential of WJ-MSCs.Results: Both ex vivo-expanded MSC populations showed similar morphologic, immunophenotypic, survival and senescence characteristics and acquired genomic alterations at low frequency during passages. WJ-MSCs exhibited higher proliferative potential, possibly due to upregulation of genes that stimulate cell proliferation along with downregulation of genes related to cell cycle inhibition. WJ-MSCs displayed inferior lineage priming and differentiation capacity toward osteocytes and adipocytes, compared to BM-MSCs. This finding was associated with differential expression of molecules related to WNT signaling, including WISP1 and sFRP4, the respective role of which in the differentiation potential of WJ-MSCs was specifically investigated. Interestingly, treatment of WJ-MSCs with recombinant human WISP1 or sFRP4 resulted in induction of osteogenesis and adipogenesis, respectively. WJ-MSCs exhibited inferior hematopoiesis-supporting potential probably due to reduced production of stromal cell-Derived Factor-1α, compared to BM-MSCs.Conclusions: Overall, these data are anticipated to contribute to the better characterization of WJ-MSCs and BM-MSCs for potential clinical applications.

Mounting evidence suggests that in myelodysplastic syndromes (MDSs) bone marrow (BM) mesenchymal stem/stromal cells (MSCs) possess abnormal characteristics and are actively involved in disease pathogenesis. Nevertheless, it is controversial whether these cells harbor clonal cytogenetic aberrations. To probe more deeply into this issue, in the present study we used conventional G-banding and FISH analysis to assess the clonal chromosomal abnormalities of hematopoietic cells (HCs) and cultured MSCs, from 29 MDS patients and 25 healthy individuals, at early, intermediate and late passage. Variable clonal cytogenetic aberrations were detected in HCs from 31% and in MSCs from 34% of MDS patients. Clonal chromosomal abnormalities in MSCs were detected even in patients without aberrations in HCs. They were mostly numerical and always differed from those in HCs from the same individual. Clonal chromosomal abnormalities did not seem to confer a proliferative and/or survival advantage to MSCs. HCs from normal donors harbored no cytogenetic abnormalities, whereas trisomy of chromosome 5 was detected in MSCs from 16% of healthy individuals, in line with other studies. Our results suggest that MDS-derived BM-MSCs are genetically unstable. The significance of this observation in the biology of MSCs and MDS pathogenesis is still unknown and warrants further evaluation.

Background Identification of fetal nucleated red blood cells (NRBCs) in maternal circulation can facilitate non-invasive prenatal diagnosis, but technical difficulties still exist. An increase in the number of circulating NRBCs, however, could indicate fetal aneuploidies or pregnancy complications. Materials and Methods The number of NRBCs was determined from 20 mL peripheral blood in 351 women in the second trimester of pregnancy after isolation by magnetic cell sorting (MACS) with anti-CD71 antibody and identification with May-Grunwald/Giemsa staining. Results An average of eight NRBCs (range 1–12) were identified among 282 women with chromosomally normal fetuses. In cases known to carry aneuploid fetuses the mean number was 35 (range 7–113), but when the fetus had trisomy 21 (n = 17) an average of 71 NRBCs were identified. Among 26 carriers of β-thalassemia, 42 NRBCs (range 22–158) were isolated. In pregnancies with abnormal Doppler findings in both uterine arteries (n = 20), 15 NRBCs (range 2–75) were isolated. Conclusion Determining the number of NRBCs in maternal circulation could represent an additional screening step for fetal aneuploidies, as long as the anemic status of the mother is taken into consideration. However, more cases with abnormal Doppler results must be investigated before this test is used for in the prediction of pregnancy complications. Copyright © 2006 John Wiley & Sons, Ltd.