Vertical transmission of maternal DNA through extracellular vesicles associates with altered embryo bioenergetics during the periconception period.

The transmission of DNA through extracellular vesicles (EVs) represents a novel genetic material transfer mechanism that may impact genome evolution and tumorigenesis. We aimed to investigate the potential for vertical DNA transmission within maternal endometrial EVs to the pre-implantation embryo and describe any effect on embryo bioenergetics. We discovered that the human endometrium secretes all three general subtypes of EV - apoptotic bodies (ABs), microvesicles (MVs), and exosomes (EXOs) - into the human endometrial fluid (EF) within the uterine cavity. EVs become uniformly secreted into the EF during the menstrual cycle, with the proportion of different EV populations remaining constant; however, MVs contain significantly higher levels of mitochondrial (mt)DNA than ABs or EXOs. During the window of implantation, MVs contain an eleven-fold higher level of mtDNA when compared to cells-of-origin within the receptive endometrium, which possesses a lower mtDNA content and displays the upregulated expression of mitophagy-related genes. Furthermore, we demonstrate the internalization of EV-derived nuclear-encoded (n)DNA/mtDNA by trophoblast cells of murine embryos, which associates with a reduction in mitochondrial respiration and ATP production. These findings suggest that the maternal endometrium suffers a reduction in mtDNA content during the preconceptional period, that nDNA/mtDNA become packaged into secreted EVs that the embryo uptakes, and that the transfer of DNA to the embryo within EVs occurs alongside the modulation of bioenergetics during implantation.

Putting reproductive rights into practice. The profile of the demand in a publicly sponsored ART program for single or female partner women in Catalonia.

PURPOSE: To evaluate the size and characteristics of the demand for a newly established, publicly sponsored, program of assisted reproduction for single women (SW) and women with a female partner (FP) in a European country. MATERIALS AND METHODS: We analysed the application forms received during the first two years and structured interviews with 300 successive non selected applicants. RESULTS: The mean sustained size of the demand was of 52.6 applications per month (sd 14) and corresponded to 0.06 % of the target population. Data from 237 applicants was evaluable. 119 (50.2 %) were SW and 118 (49.8 %) were FP. The median age was 36 years, 36.5 years for SW and 34 years for FP (p < 0.001, Mann-Whitney). Clinically 18.6 % of women presented irregular cycles, and 17.8 % of women had undergone hysterosalpingography (HSG), with a 14.3% prevalence of tubal dysfunction. CONCLUSIONS: A publicly sponsored program for Assisted Reproduction for SWFP should establish clear inclusion criteria, especially as regards to age, ovarian reserve, techniques offered, and the number of cycles to obtain the maximal efficiency. Further research specific for this group is required to ensure that they receive adequate care and ultimately to fulfil their reproductive rights.