GENERAL MEDICAL NEWS
The staff of The Reproductive Times here offers brief referenced notes on interesting general medical and scientific news with broad relevance to reproductive medicine and biology. Some of these news items may become subjects of more detailed reporting in The Reproductive Times on later occasions. The purpose of these short notifications is to give readers the opportunity to get immediately more detailed information by looking up the reference of the note.
A specific molecular trigger for Multiple Sclerosis (MS) and autoimmune diseases in general?
Regulatory T cells (Tregs) – characterized as CD4+FOXP3+ – have for 20 years now been known to play a central role in preventing autoimmunity. How they do it, has, however, been unknown. Yale University researchers and U.S. and Japanese collaborators have now identified the primate-specific short isoform of PR domain zinc finger protein (PRDM1-S) as a trigger of loss of immune regulation in MS but is also found in other autoimmune diseases. Upregulation of the protein apparently leads to interaction of several genetic and environmental factors including high salt uptake and appears to be a key driver of dysfunction of Tregs in, possibly, all autoimmune diseases.1
REFERENCE
1. Sumida TS, et al. Sci Transl Med 2024;16(762): eadp1720.doi: 101126/scitranslmed.adp1720
Does premature menopause affect causes of mortality and life span in affected women?
Considering that the question of whether ovarian aging is reflective of general aging and longevity of women is likely one of the most basic unanswered questions in reproductive medicine, a recent paper in Menopause on first impression seemed to offer an answer; in execution, it unfortunately failed to do so, for two principal reasons: First, the comparison the study offered was between women with premature menopause and men, rather than between women with and without premature menopause. And second, the authors paradoxically failed to recognize the potential significance of their findings when concluding “that women with premature menopause demonstrated a lower risk for all-cause mortality than men; but their lifespan advantage was insignificant.”1 What the authors (and peer-review) in this context apparently overlooked was the fact that women are expected to have longer life spans. That they did not show longer life spans in this study, therefore, may indeed suggest that premature menopause may be associated with shortened life spans.
REFERENCE
1. Zailing X, Russel K. Menopause 2024; 10.1097/GME.0000000000002412.
A better way to manage stem-cell transplants?
Researchers at New York’s Albert Einstein College of Medicine just reported in Science magazine a potentially important advance in transplantation of hematopoietic stem cells (HSCs) which lifelong have the function of producing all types of blood cells.1 This happens through so-called “stem cell mobilization,” a process in which the bone marrow constantly releases small amounts of HSCs into the peripheral blood. This process can, for example, be enhanced through hematopoietic cytokine signaling with granulocyte colony-stimulating factor (G-CSF) and has been used to increase the number of harvested HSCs in peripheral blood for the treatment of the myelodysplastic syndrome, cancers, autoimmune diseases, and in reproductive medicine, in Asherman’s syndrome.2
The investigators in this study discovered that some HSCs engage in trogocytosis, a process involving the exchange of plasma membrane portions between cells between immune cells, including B and T lymphocytes, NK cells, and basophils. Lymphocytes conjugated to antigen-presenting cells, for example, in this way extract surface molecules from other cells in order to express them on their own surface. In this study, the authors demonstrated that HSCs acquired proteins in this way from bone marrow-associated macrophages which were associated with retention of HSCs in bone marrow, while HSCs without these proteins on their surface would be released into the periphery. These findings, therefore, should allow for even better HSC mobilization strategies in the near future.
REFERENCES
1. Gao et al., Science 2024;385(6709): eadp2065.doi: 10.1126/science.adp2065.
2. Santamaria et al., Hum Reprod 2016;31(5):1087-1096
The ethics of prenatal genetic testing – is more information always better?
As an introduction to this news item we, first, have to introduce the two participants in a fascinating interview,1 the interviewer, Molly McDonough, who is the Associate Editor of the Harvard Medicine magazine, and the interviewee, Vardit Ravitsky, PhD, who a little over a year ago became the new president and CEO of the prestigious Hastings Center, a nonprofit bioethics research institute in Westchester, while maintaining her professorial academic appointment at the University of Montreal—her prior fulltime academic position—as well as her parttime position as senior lecturer on global health and social medicine at Harvard University.
While this interview will likely become subject of a more detailed report in The Reproductive Times, here is its essence: What it so interesting is that it addressed the very personal experience of a highly educated bioethicist whose research for years has focused on new reproductive technologies. Several years ago, pregnant at age 40, a routine blood screening test (called NIPT, non-invasive prenatal testing) revealed that her pregnancy had a 1 in 40 chance of being a Down’s syndrome (Trisomy 21). The recommendation she received was to undergo a more invasive diagnostic test like an amniocentesis (if the difference between a screening and diagnostic test is not absolutely clear, today’s preceding article by Dr. Barad explains it well) which increases the risk of a spontaneous miscarriage.
What is interesting is not so much her decision at that point, but her earlier decision to undergo the NIPT test in the first place, “because it felt empowering.” Once she started thinking about the implications at a societal scale, however, the decision “felt more problematic.”
Explaining this dichotomy and discussing ethical considerations of several other prenatal tests offered by the laboratory testing industry in growing numbers makes a fascinating read we strongly recommend.
REFERENCE
1. McDonough M. Harvard Medicine Magazine, August 2024. https://magazine.hms.harvard.edu/articles/ethics-prenatal-genetic-testing