Single-cell multiplex chromatin and RNA interactions in ageing human brain.

Dynamically organized chromatin complexes often involve multiplex chromatin interactions and sometimes chromatin-associated RNA1-3. Chromatin complex compositions change during cellular differentiation and ageing, and are expected to be highly heterogeneous among terminally differentiated single cells4-7. Here we introduce the multinucleic acid interaction mapping in single cells (MUSIC) technique for concurrent profiling of multiplex chromatin interactions, gene expression and RNA-chromatin associations within individual nuclei. When applied to 14 human frontal cortex samples from older donors, MUSIC delineated diverse cortical cell types and states. We observed that nuclei exhibiting fewer short-range chromatin interactions were correlated with both an 'older' transcriptomic signature and Alzheimer's disease pathology. Furthermore, the cell type exhibiting chromatin contacts between cis expression quantitative trait loci and a promoter tends to be that in which these cis expression quantitative trait loci specifically affect the expression of their target gene. In addition, female cortical cells exhibit highly heterogeneous interactions between XIST non-coding RNA and chromosome X, along with diverse spatial organizations of the X chromosomes. MUSIC presents a potent tool for exploration of chromatin architecture and transcription at cellular resolution in complex tissues.

Effect of single versus grouped culture of human cumulus-oocyte complexes in PCOS women treated with biphasic in vitro maturation: A sibling oocyte pilot study.

Purpose: This study investigated the differences in the maturation rate of single versus grouped cumulus-oocyte complexes (COCs) culture methods for capacitation in vitro maturation (CAPA-IVM) in women with polycystic ovary syndrome (PCOS). Methods: This study was performed at My Duc Phu Nhuan Hospital, Vietnam from October 1, 2020 to October 24, 2021. Women aged 18-37 years with a diagnosis of PCOS were recruited. COCs from each woman were randomly divided into two groups: single or grouped culture during CAPA-IVM culture. The primary outcome was the maturation rate. Results: A total of 322 COCs from 15 eligible women included were randomly assigned to the two study groups. The maturation rate was comparable between the single and grouped culture groups (61.3% vs. 64.8%; p = 0.56). There were no significant differences in the number of 2-pronuclei fertilized oocytes, number of day-3 embryos, and number of good-quality embryos in the two culture method groups. In the single culture group, COCs morphology was associated with the day-3 embryo formation rate but not the maturation rate. Conclusions: Comparable oocyte maturation and embryology outcomes between single and grouped COCs culture utilizing sibling COCs derived from women with PCOS suggest the feasibility of both methods for CAPA-IVM culture.

Embryological and clinical outcomes in couples with severe male factor infertility versus normozoospermia.

OBJECTIVE: This study evaluated embryological and clinical outcomes in couples with severe male factor infertility versus those with normozoospermia undergoing ICSI and in vitro fertilisation. METHODS: This multicentre, retrospective cohort study included all couples who had undergone autologous ICSI cycles at My Duc Hospital and My Duc Phu Nhuan Hospital in Vietnam between January 2018 and January 2021 (female age < 35 years and males with severe male factor or normozoospermia based on the World Health Organization 2010 criteria). The primary outcome was the cumulative live birth rate after the first ICSI cycle. RESULTS: A total of 1296 couples were included, including 648 with severe male factor infertility and 648 with normozoospermia. The number of two pronuclei zygotes, embryos, and frozen embryos was significantly lower in couples with severe male factor infertility compared with normozoospermia (p < 0.05). In contrast, there were no significant differences between the two groups with respect to cumulative pregnancy outcomes, including the live birth rate, and secondary outcomes including clinical pregnancy rate, ongoing pregnancy rate, and miscarriage rate. CONCLUSION: Severe male factor infertility appeared to have an impact on the fertilisation and early developmental potential of embryos, but sperm quality did not affect cumulative clinical fertility outcomes.