Genetics and IVF Institute

Major depressive disorder (MDD) is frequently comorbid with mild cognitive impairment (MCI), yet its molecular basis remains unclear. This study aimed to identify shared differentially expressed genes (DEGs) and biological pathways that may underlie the comorbidity between MDD and MCI. Using integrative bioinformatics approaches applied to transcriptomic datasets, we sought to uncover molecular biomarkers that could inform early diagnosis and provide novel targets for mechanism-based therapeutic strategies. Transcriptomic datasets from MDD (GSE58430) and MCI (GSE140831) patients were analyzed to identify DEGs. Functional enrichment analyses were performed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Protein-protein interaction (PPI) networks were constructed to identify core genes. A total of 301 DEGs were shared between MDD and MCI. Gene Ontology and KEGG enrichment analyses revealed key biological processes involved in neuroinflammation, oxidative stress, synaptic dysfunction, and apoptotic signaling. The PPI network analysis identified nine hub genes with high connectivity: HSP90AB1, CDC42, NFKB1, CD8A, CALM3, PARP1, CD44, H2BC21, and MYH9. These findings reveal shared molecular biomarkers and pathways linking MDD and MCI, providing insights into their comorbidity. The identified core genes, particularly PARP1 and CDC42, may serve as novel targets for early diagnosis and mechanism-based therapeutic strategies in psychiatry and neurodegenerative disorders.

Purpose: Phosphatidylserine exposed on live and motile sperm is necessary for sperm:egg fusion, and emerging data suggest it is a biomarker for fertilization competent sperm. Men with varicocele often display infertility, and one of the known causes is poor sperm quality. Here, we sought to determine whether the percentage of phosphatidylserine-positive live sperm (PS+ live sperm) could serve as a reliable indicator of male fertility. Materials and Methods: Semen samples from cryo-banked pregnancy-proven donors, from self-identified pregnancy-reported donors, and from men seeking infertility treatment for varicocele were analyzed for phosphatidylserine exposure on live sperm. Semen samples were also analyzed premicrosurgical and postmicrosurgical varicocele repair to determine whether varicocele repair led to a change in the percentage of PS+ live sperm. Results: Semen samples from “pregnancy-proven” donors (n = 31) had 82% ± 2% PS+ live sperm and samples from “self-identified pregnancy-reported” donors (n = 34) had 87% ± 1%. Men presenting with a varicocele (n = 80) had significantly lower PS+ live sperm with 68% ± 3%. PS+ live sperm correlated with reported pregnancies in patients with varicocele, whereas total motile sperm count did not. Varicocele repair (n = 10) led to a significant increase in PS+ live sperm, and 2 of the patients reported pregnancies after varicocele repair. Conclusions: These results suggest that the percentage of PS+ live sperm in an ejaculate correlates with male fertility status and could help in guiding treatment options for patients with varicoceles.

Huntington’s disease (HD) is fatal neurodegenerative disease caused by a (CAG) triplet repeat expansion in the Huntingtin (HTT) gene. Inheritance pattern of the disease is autosomal dominant and onset depending on triplet repeat count. Transgenerational HD transmission can be avoided by preimplantation genetic diagnosis (PGD). Here, we report the first preimplantation genetic testing case for monogenic disease, in Latvia. The result of our work led to the birth of healthy child with normal HTT alleles in his genome. We describe a PGD strategy and testing algorithm that can be applied to any couple at risk of transmitting monogenic disease.

The purpose of the present study was to evaluate the safety of MicroSort (MicroSort Division, GIVF, Fairfax, VA, USA) sperm sorting by monitoring major malformations in infants and fetuses conceived using sorted spermatozoa. Data were collected in a prospective protocol with monitoring that began from conception through birth until 1 year of life. Comprehensive ascertainment identified fetuses and stillbirths with malformations after 16 weeks gestation, pregnancies terminated for malformations and babies with major malformations. Outcomes in MicroSort pregnancies were compared with outcomes in published studies that used active and comprehensive ascertainment of malformations in the general population and in pregnancies established after assisted reproduction. Using comprehensive outcomes from all pregnancies, the rate of major malformations in MicroSort pregnancies conceived after IVF with or without intracytoplasmic sperm injection was 7.8%; this did not differ significantly from the rates reported in the three assisted reproductive technology control studies not associated with MicroSort (8.6%, 9.2% and 8.3%). Similarly, the rate of major malformations in MicroSort pregnancies initiated with intrauterine insemination was 6.0%, not significantly different from that reported in non-assisted reproductive technology pregnancies not associated with MicroSort (6.9%, 4.6% and 5.7%). Prospective record review of pregnancy outcomes and paediatric evaluation to 1 year indicate no association between MicroSort sperm sorting and major malformations.