ABSTRACT
BACKGROUND: A variety of autoimmune diseases, including MS, amplify sex-based physiological differences in immunological responsiveness. Female MS patients experience pathophysiological changes during reproductive phases (pregnancy and menopause). Sex hormones can act on immune cells, potentially enabling them to modify MS risk, activity, and progression, and to play a role in treatment. METHODS: Scientific papers (published between 1998 and 2021) were selected through PubMed, Google Scholar, and Web of Science literature repositories. The search was limited to publications analyzing the hormonal profile of male and female MS patients during different life phases, in particular focusing on sex hormone treatment. RESULTS: Both men and women with MS have lower testosterone levels compared to healthy controls. The levels of estrogens and progesterone increase during pregnancy and then rapidly decrease after delivery, possibly mediating an immune-stabilizing process. The literature examined herein evidences the neuroprotective effect of testosterone and estrogens in MS, supporting further examinations of their potential therapeutic uses. CONCLUSIONS: A correlation has been identified between sex hormones and MS clinical activity. The combination of disease-modifying therapies with estrogen or estrogen plus a progestin receptor modulator promoting myelin repair might represent an important strategy for MS treatment in the future.
ABSTRACT
Persistence of a fetal thickened nuchal translucency (NT), one of the most sensitive and specific individual markers of fetal disorders, is strongly correlated with the possibility of a genetic syndrome, congenital infections, or other malformations. Thickened NT can also be found in normal pregnancies. Several of its pathophysiological aspects still remain unexplained. Metabolomics could offer a fresh opportunity to explore maternal-foetal metabolism in an effort to explain its physiological and pathological mechanisms. For this prospective case-control pilot study, thirty-nine samples of amniotic fluids were collected, divisible into 12 euploid foetuses with an enlarged nuchal translucency (>NT) and 27 controls (C). Samples were analyzed using gas chromatography mass spectrometry. Multivariate and univariate statistical analyses were performed to find a specific metabolic pattern of >NT class. The correlation between the metabolic profile and clinical parameters was evaluated (NT showed an R2 = 0.75, foetal crown-rump length showed R2 = 0.65, pregnancy associated plasma protein-A showed R2 = 0.60). Nine metabolites significantly differing between >NT foetuses and C were detected: 2-hydroxybutyric acid, 3-hydroxybutyric, 1,5 Anydro-Sorbitol, cholesterol, erythronic acid, fructose, malic acid, threitol, and threonine, which were linked to altered pathways involved in altered energetic pathways. Through the metabolomics approach, it was possible to identify a specific metabolic fingerprint of the fetuses with >NT.
