Letter to President Biden and Secretary Designate of HHS, Xavier Becerra
In a published letter (_Santoro et al Reprod Sciences 2021; https:/doi.org/10.1007/s43032-021-00491-_9), a small group of prominent physicians, scientists, and ethicists in reproductive medicine urged the new administration to reverse a decision made by the Human Fetal Tissue Ethics Advisory Board. This decision withheld funding for 13 out of 14 NIH grants that were favorably peer reviewed in the Summer of 2020. It will be interesting to see whether this very appropriate request will be granted. Contrary to widely held beliefs, Democratic administration have in the past not necessarily been much more favorable in supporting reproductive research than Republicans. We hope for the best!
Specific T cells linked to fetal loss and gestational diabetes in pregnancy
A group of multinational investigators just published an interesting paper in Nature (Paolino et al., 2021;589:442-447), demonstrating that the so-called osteoclast differentiation receptor, RANK, promotes the hormone-mediated development of thymic Treg cells during pregnancy and expands their functional role in developing gestational diabetes and transgenerational metabolic rewiring of glucose hemostasis. In mouse models Rank depletion in the thymus reduces accumulation of natural Treg cells in the placenta and increases miscarriages by also decreasing Treg cells in visceral adipose tissue, increases the size of adipocytes, tissue inflammation, maternal glucose intolerance, fetal macrosomia and long-lasting transgenerational alteration of glucose hemostasis. This paper, therefore, offers a potential explanation for a Scandinavian paper we reported about in “Did you know?” that reported that chronic maternal conditions, like DM and autoimmune diseases, predispose to CP. And, on a sidenote, uncontrolled DM is also associated with increased miscarriage risk.
Mosaicism is inherent to the human placenta
A just published study in Nature (Coorens et al., Nature 2021; https://doi.org/10.1038/s41586-021-03345-1) offers further evidence that mosaicism (presence of limited numbers of chromosomal abnormal cells) in human embryos and their (later) placentas is a completely normal finding. The authors demonstrated that developmental bottlenecks genetically segregate trophectodermal (extraembryonic) from lineages of the inner cell mass (embryonic), likely, normalize zygotic aneuploidies. The authors, indeed, were able to directly observe a case of mosaic trisomy rescue. They concluded that the placenta, derived from the trophectoderm, is characterized by extensive mutagenesis and that mosaicism represents a typical feature of placental development.
This study, of course, has major relevance for the ongoing debate in IVF about the utilization of preimplantation genetic testing for aneuploidy (PGT-A), a frequent subject in the VOICE. This study reported findings, of course, that further support the position CHR has taken on the subject for decades because the placenta derives from the trophectoderm, where embryos are biopsied from. The inner cell mass, in turn becomes the fetus and baby. This study confirms with much more detail what has been known for decades, - namely that placentae in completely normal births frequently contain an island of cells with chromosomal abnormalities. A paper in press in another Nature journal, authored by investigators from Rockefeller University and CHR, should appear in print within weeks, and will further comment on this subject with important new information.
Norbert Gleicher, MD, FACOG, FACS
Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned specialist in reproductive endocrinology, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.
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