Anxiety and depression-like behaviours are more frequent in aged male mice conceived by ART compared with natural conception.

The number of children born after assisted reproductive technology (ART) is accumulating rapidly, and the health problems of the children are extensively concerned. This study aims to evaluate whether ART procedures alter behaviours in male offspring. Mouse models were utilized to establish three groups of offspring conceived by natural conception (NC), in vitro fertilization and embryo transfer (IVF-ET), and frozen-thawed embryo transfer (IVF-FET), respectively. A battery of behaviour experiments for evaluating anxiety and depression levels, including the open field test (OFT), elevated plus maze (EPM) test, light/dark transition test (L/DTT), tail suspension test (TST), forced swimming test (FST), and sucrose preference test (SPT) was carried out. Aged (18 months old), but not young (3 months old), male offspring in the IVF-ET and IVF-FET groups, compared with those in the NC group, exhibited increased anxiety and depression-like behaviours. The protein expression levels of three neurotrophins in PFC or hippocampus in aged male offspring from the IVF-ET and IVF-FET groups reduced at different extent, in comparison to NC group. RNA sequencing (RNA-Seq) was performed in the hippocampus of 18 months old offspring to further explore the gene expression profile changes in the three groups. KEGG analyses revealed the coexisted pathways, such as PI3K-Akt signalling pathway, which potentially reflected the similarity and divergence in anxiety and depression between the offspring conceived by IVF-ET and IVF-FET. Our research suggested the adverse effects of advanced age on the psychological health of children born after ART should be highlighted in the future.

The effect of blastomere loss during frozen embryo transfer on the transcriptome of offspring's umbilical cord blood.

Blastomere loss is a common issue during frozen-thawed embryo transfer (FET). Our previous study showed that blastomere loss was associated with an increased risk of small-for-gestational-age (SGA) neonates. The present study assessed the impact of blastomere loss during cryopreservation by comparing the mRNA profiles of umbilical cord blood of FET offspring from the prospective cohort study. Umbilical cord blood samples were collected from 48 neonates, including 12 from the loss group, 11 from the intact group, and 25 from the matched spontaneous pregnancy group. RNA-seq technology was used to compare the global gene expression profiles of the lymphocytes. Then, we used TopHat software to map the reads and quantitative real-time PCR to validate some important differentially expressed genes (DEGs). We identified 92 DEGs between the loss group and the spontaneous pregnancy group, including IGF2 and H19. Ingenuity Pathway Analysis (IPA) showed that the DEGs were most affected in the blastomere loss group. Downstream analysis also predicted the activation of organismal death pathways. In conclusions, our pilot study sheds light on the mechanism underlying how human blastomere loss may affect offspring at the gene expression level. These conclusions are, however, only suggestive, as the current study is based on a very limited sample size and type or nature of biological samples. Additional studies with larger sample sizes and independent experiments with placental samples should be conducted to verify these findings.

Effect of Frozen-Thawed Embryo Transfer on the Metabolism of Children in Early Childhood.

BACKGROUND: As a routine procedure in assisted reproductive technology (ART), it is crucial to assess the safety of frozen and thawed embryo transfer (FET). We aimed to investigate the metabolic profile of children conceived through FET in their early childhood. METHOD: A total of 147 children between the age of 1.5 and 4 years old, conceived through FET or naturally conceived (NC), were recruited. A total of 89 children, 65 in the FET group and 24 in the NC group (matched with the FET group based on children's BMI) were included in the final statistical analysis of biochemical markers and metabolomics. RESULTS: Children conceived through FET had a lower level of fasting insulin level and HORM-IR and a higher level of fasting glucose and APOE as compared to children naturally conceived. Metabolomics showed that there were 16 small differential metabolites, mainly including amino acids, carnitines, organic acids, butyric, and secondary bile acid between two groups, which enriched in Nitrogen metabolism, Butanoate metabolism, Phenylalanine metabolism, and D-Arginine and D-ornithine metabolism pathways. CONCLUSION: Although the FET group had a significantly higher level of APOE and fasting glucose, it cannot yet be considered that children in the FET group had an obvious disorder of glucose and lipid metabolism. However, the potentially more active intestinal flora and lower carnitine levels of children in the FET group suggested by metabolomics are worth further exploration.