INTERESTING RESEARCH NEWS
How many mammals can slow-down the development of embryos around blastocyst stage?
It does not happen often that so many superstars in reproductive biology from all over Europe publish a paper together, as in a recent paper in Cell (1). But this was not even the most interesting aspect of the paper. The most interesting thing about this paper clearly was what it reported!
It is well known that many mammals can interrupt embryo development in a reversible way (called diapause), and this usually happens at the blastocyst stage. In mice, this is achieved by decreasing the activity of the mTOR signaling pathway. Whether this ability is generally conserved in mammals—and, of course, especially in humans—was, however, unknown.
In this quite amazing paper, the authors now demonstrated that decreasing the activity of the mTOR signaling pathway in the human experience induced pluripotent stem cells (hPSCs) as well as blastoids (made from stem cell lines) to—similarly—enter a dormant state, characterized by limited proliferation, developmental progression, and capacity to attach to endometrial cells. In other words, human blastoids produced from stem cell lines, under mTOR inhibition, demonstrated a diapause-like response that has never before been described in human preimplantation-stage embryos.
In vitro assays demonstrated very convincingly that, similar to other species, the ability to enter dormancy is likely also active around the blastocyst stage in human embryos and is reversible at both functional and molecular levels.
The resulting theoretical possibility to pace human blastocyst development has, of course, quite amazing potential implications for IVF practice. Blastoids in such dormancy, for example, demonstrated altered developmental progression and attachment. Mouse and human cells, moreover, demonstrated species-specific metabolic profiles in dormancy.
Likely one of the most exciting research papers for IVF practice we have read in a long time, and we are very proud to be able to announce that one of the senior authors, Nicolas Rivron, PhD, from the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter, will this year be a member of the faculty at the annual Foundation for Reproductive Medicine Conference (FRMC) in NYC, which the Foundation and the CHR this year co-sponsor on December 5-7, 2025, at the Metropolitan Club.
Reference
1. Iyer et al.,., Cell 2024;187:6566-6583
Exosomal miR-302b for rejuvenation?
In another quite remarkable paper in Cell Metabolism, Chinese investigators demonstrated that human embryonic stem cell-derived exosomes (hESC-Exos) reversed senescence by restoring the proliferative capacity of SnCs in vitro.
Graphic abstract of here discussed paper (1)
hESC-Exos treatment in aging mice remodeled the proliferative landscape of senescent cells, leading to rejuvenation, as evidenced by extended lifespan, improved physical performance, and reduced aging markers. miR-302b was identified as enriched in hESC-Exos that specifically targeted the cell cycle inhibitors Cdkn1a and Ccng2. miR-302b treatment also reversed the proliferative arrest of senescent cells in vivo, resulting in rejuvenation without safety concerns over a 24-month observation period.
These results, summarized above in the graphic abstract from the paper, demonstrate that exosomal miR-302b has the potential to reverse cellular senescence. This finding, of course, has major potential clinical significance if it can be reconfirmed in the human experience. It then could offer a promising approach to mitigate senescence-related pathologies as well as the aging process in general. And all of that is obviously applicable to the ovaries—at least theoretically!
Reference
1. BI et al. Cell Metab 2025;37:1-5