The application of PGT-A for carriers of balanced structural chromosomal rearrangements

Abstract

The aim of this study was to analyze differences in chromosomal aberrations and euploidy in embryos of each translocation type and gender of carrier in the case series of 10 couples with balanced translocations who underwent IVF with embryos trophectoderm (TE) biopsy and PGT-A to detect chromosomal aberrations. This is a Case Series (Retrospective study). In each case, controlled ovarian hyperstimulation, oocyte insemination with intracytoplasmic sperm injection (ICSI) and cultivation gave multiple blastocysts, that underwent trophectoderm (TE) biopsy with PGT-A analysis using aCGH and NGS. Number of total unbalanced translocations compared to the number of sporadic aneuploid embryos was 39.6% to 39.6% (50% to 50% of all 37 aneuploid embryos). The highest euploidy rate was in male carrier group – 26.7% and the lowest in the Robertsonian translocation carrier group – 18.2%. Sporadic aneuploidy – 68.2% was highest in Robertsonian translocation carrier group and lowest in female group – 11.1%. Chromosomal aberrations related to translocation were highest in female carrier group – 77.8% and lowest in Robertsonian translocation carrier group – 13.6%. Our study showed that expectancy of total embryo aneuploidy rates will be higher in carriers, than in people with normal karyotype. The prevalence of chromosomal aberrations related to translocation was 4.5 times higher in Reciprocal carrier group than in Robertsonian translocation carrier group. Among maternal and paternal carrier groups, the embryos from female carriers had the lowest euploidy rate, unbalanced translocation rate 4.7 times higher than in the male carrier group and higher total aneuploidy rates.     

The Modulatory Role of the Lateral Septum on Neuroendocrine and Behavioral Stress Responses

The lateral septum (LS) has been shown to have a key role in emotional processes and stress responses. However, the exact role of the LS on stress modulation is not clear, as previous lesion studies mostly used electrolytic lesions, thereby destroying the whole septal area, including medial components and/or fibers of passage. The aim of the present study was therefore, to investigate the effects of selective excitotoxic ablation of the LS on neuroendocrine and behavioral stress responses in rats. Bilateral ibotenic acid lesions of the LS increased hypothalamo–pituitary–adrenocortical (HPA) axis responses to forced swim stress indicated by enhanced plasma ACTH and corticosterone responses and higher stress-induced c-Fos-like immunoreactivity in the paraventricular hypothalamic nucleus. Moreover, LS-lesioned animals showed a more passive coping style in the forced swim test indicated by increased floating and reduced struggling/swimming behavior compared with sham-lesioned controls. Interestingly, intraseptal corticosteroid receptor blockade modulated behavioral stress coping but failed to change HPA axis stress responses. Further experiments aimed at elucidating underlying neurochemical mechanisms revealed that intraseptal administration of the selective 5-HT_1A receptor antagonist WAY-100635 increased and prolonged stress-induced ACTH and corticosterone levels mimicking lesion effects, while the agonist 8-OH-DPAT suppressed HPA axis activity facilitating the inhibitory role of the LS. In addition, 8-OH-DPAT-injected animals showed increased active and decreased passive coping strategies during forced swimming suggesting antidepressant efficacy. Taken together, our data suggest that the LS promotes active stress coping behavior and is involved in a HPA-inhibitory mechanism that is at least in part mediated by septal 5-HT_1A receptors and does not involve a glucocorticoid mediated feedback mechanism.