Human mesenchymal stem cells increase LLC metastasis and stimulate or decelerate tumor development depending on injection method and cell amount.

Mesenchymal stem cells (MSCs) being injected into the body can stimulate or decelerate carcinogenesis. Here, the direction of influence of human placenta-derived MSCs (P-MSCs) on the Lewis lung carcinoma (LLC) tumor development and metastatic potential is investigated in C57BL/6 mice depending on the injection method. After intramuscular co-inoculation of LLC and P-MSCs (LLC + P-MSCs), the growth of primary tumor and angiogenesis are slowed down compared to the control LLC on the 15th day. This is explained by the fact of a decrease in the secretion of proangiogenic factors during in vitro co-cultivation of an equal amount of LLC and P-MSCs. When P-MSCs are intravenously (i.v.) injected in the mice with developing LLC (LLC + P-MSCs(i.v.)), the tumor growth and angiogenesis are stimulated on the 15th day. A highly activated secretion of proangiogenic factors by P-MSCs in a similar in vitro model can explain this. In both the models compared to the control on the 23rd day, there is no significant difference in the tumor growth, while angiogenesis remains correspondingly decelerated or stimulated. However, in both the models, the total volume and number of lung metastases constantly increase compared to the control: it is mainly due to small-size metastases for LLC + P-MSCs(i.v.) and larger ones for LLC + P-MSCs. The increase in the rate of LLC cell dissemination after the injection of P-MSCs is explained by the disordered polyploidy and chromosomal instability, leading to an increase in migration and invasion of cancer cells. After LLC + P-MSCs co-inoculation, the tumor cell karyotype has the most complex and heterogeneous chromosomal structure. These findings indicate a bidirectional effect of P-MSCs on the growth of LLC in the early periods after injection, depending on the injection method, and, correspondingly, the number of contacting cells. However, regardless of the injection method, P-MSCs are shown to increase LLC aggressiveness related to cancer-associated angiogenesis and metastasis activation in the long term.

Chromosomal abnormalities in products of conception of first-trimester miscarriages detected by conventional cytogenetic analysis: a review of 1000 cases.

PURPOSE: The purpose of this study is to perform a retrospective analysis of types and frequencies of chromosomal abnormalities detected by conventional cytogenetic studies in first-trimester miscarriages after spontaneous conception and IVF. METHODS: Standard cytogenetic analysis of GTG-banded chromosomes obtained from products of conception (POCs): semi-direct and short-term cultured chorionic villi or long-term cultured fetal mesodermal cells. RESULTS: 50.1% of first-trimester miscarriages in the studied group had chromosomal abnormalities: 59.7% of trisomies, 22% of poliploidies, 7.5% of monosomies, 7% of unbalanced structural abnormalities, and 3.8% of multiple aneuploidies. An increase in the frequency of chromosomally abnormal miscarriages was observed in the group of women above 40 when compared to groups of women under 35 (P < 0.05). No difference in frequencies and types of chromosomal abnormalities in POCs of miscarriages after ICSI and spontaneous conception was observed. CONCLUSIONS: Approximately, 50% of first-trimester miscarriages have chromosomal abnormalities which can be detected by conventional cytogenetic analysis. The presence of chromosomal abnormality may explain the cause of miscarriage, improving the reproductive counseling and planning.

Chromosomal segregation in sperm of Robertsonian translocation carriers.

PURPOSE: To study meiotic segregation patterns of Robertsonian translocations in sperm of male carriers and to assess the frequencies of unbalanced sperm formation. METHODS: FISH with combination of probes to detect all the variants of meiotic segregation was performed on decondensed sperm nuclei of 5 carriers of der(13;14), 3 carriers of der(14;21) and one carrier of a rare der(13;21) translocation. RESULTS: The frequency of sperm with alternate segregation and normal/balanced chromosomal complement ranged from 68 % to 94.4 % (mean 79.2 ± 8.4). Adjacent segregation was detected in 17.9 ± 7.3 % of sperm (from 5.6 % to 29 %). No significant differences in frequencies of gametes with nullisomies and disomies of chromosomes involved in translocations were observed. The mean frequency of 3:0 segregation products was 2.5 ± 1.4 %. CONCLUSIONS: All analyzed patients showed homogenous segregation pattern with clear predominance of alternate segregation resulting in normal/balanced sperm production. Still, from 5.8-32 % (mean 20.4 ± 8.3 %) of sperm was unbalanced, which is the evidence of the increased risk of unbalanced offspring in carriers of Robertsonian translocations. Our results highlight the importance of genetic counseling of Robertsonian translocation carriers prior to ICSI or IVF.

Chromosomal abnormalities in patients with oligozoospermia and non-obstructive azoospermia.

PURPOSE: To assess the frequency and types of chromosomal abnormalities in 204 Ukrainian patients with non-obstructive azoospermia and oligozoospermia and 87 men with normozoospermia. METHODS: Cytogenetic studies were performed on peripheral blood lymphocyte samples of 164 men with oligozoospermia, 40 men with non-obstructive azoospermia and 87 men with normozoospermia attending infertility clinic. RESULTS: Chromosomal abnormalities were detected in 17% of patients with sperm disorders: in 35% of men with azoospermia and in 12.7% of men with oligozoospermia. The frequency of chromosomal abnormalities in patients with sperm disorders was significantly higher, than in patients with normozoospermia (P = 0.0001). An increase in the incidence of chromosomal abnormalities with the decrease of sperm count was observed. Chromosomal abnormalities were detected in 1.1% of patients with normozoospermia, 6.5% of patients with mild oligozoospermia (sperm count 5-15 × 10(6)/ml), 18.4% of patients with severe oligozoospermia (sperm count <5 × 10(6)/ml) and 35% of patients with azoospermia. A significant increase in the frequency of chromosomal abnormalities in patients with severe oligozoospermia was observed when compared to mild oligozoospermia (P = 0.01). A statistically significant association (P = 0.02) of chromosomal abnormalities and sex chromosome abnormalities (P = 0.0001) with azoospermia when compared to oligozoospermia was observed. CONCLUSIONS: Our results highlight the importance of cytogenetic studies in patients with oligozoospermia (both mild and severe) and non-obstructive azoospermia. The presence of chromosomal abnormalities influences significantly the fertility treatment protocols, as well as provides a definite diagnosis to couples suffering from infertility.