Neuroscience in transgender people : an update

Transgender persons identify with a gender different from the one they were assigned at birth. Although describing oneself as transgender is not a new phenomenon, media attention has lately been increasing exponentially, thanks to progressive changes in laws and change in societal attitudes. These changes also allow more people nowadays to (openly) identify as transgender and/or seek gender-affirming treatment. However, simultaneously, not much is presently understood about the underlying neurobiology, and specifically the brain structure and brain function of transgender persons. One major question in neuroimaging and neuroscience has been to determine whether, at the brain level, transgender people resemble more their gender identity, their sex assigned at birth, or have a unique neural profile. Although the evidence is presently inconsistent, it suggests that while the brain structure, at least before hormonal treatment, is more similar to sex assigned at birth, it may shift with hormonal treatment. By contrast, on “sex-stereotypical tasks,” brain function may already be more similar to gender identity in transgender persons, also before receiving gender-affirming hormone treatment. However, studies continue to be limited by small sample sizes and new initiatives are needed to further elucidate the neurobiology of a ‘brain gender’ (sex-dimorphic change according to one’s gender).Transgender-Personen identifizieren sich mit einem anderen Geschlecht als dem bei der Geburt zugewiesenen. Obwohl Menschen, die sich mit einem anderen Geschlecht identifizieren, kein neues Phänomen sind, so ist die mediale Aufmerksamkeit in den letzten Jahren diesbezüglich exponentiell gestiegen. Dies ist auch den gesetzlichen Verbesserungen und einer Veränderung in der gesellschaftlichen Einstellung zu dem Thema zu verdanken. Zur gleichen Zeit aber weiß man noch nicht viel über die Gehirnstruktur und Gehirnfunktion bei transgender Menschen. Eine Hauptfrage in den Neurowissenschaften ist es, ob die Gehirne von Transgender-Personen jenen ähneln des Geschlechtes, dem sie bei der Geburt zugewiesen wurden, des Geschlechtes mit dem sie sich identifizieren, oder ob sie ein unabhängiges neuronales Profil aufzeigen. Obwohl die Befunde derzeit widersprüchlich sind, zeigen sie in die Richtung, dass sich die Gehirnstruktur vor der hormonellen Behandlung nur unwesentlich verändert. Auf der anderen Seite gleicht die neuronale Aktivität bei “geschlechtstypischen Aufgaben” von Transgender-Personen der neuronalen Aktivität ihres identifizierten Geschlechts (auch schon vor der Hormonbehandlung). Trotzdem sind Studien weiterhin limitiert, da sie oft mit kleinen Stichproben auskommen müssen und neue Initiativen zur Bestätigung der ersten Befunde nötig sind

Lower serum estradiol levels in assigned female at birth transgender people with initiation of testosterone therapy : results from the European Network for the Investigation of Gender Incongruence

Purpose: Concerns have been raised about undesired estrogenic effects in assigned female at birth (AFAB) transgender people on testosterone therapy. How serum estradiol levels change after initiation of testosterone therapy and if these levels should be monitored remain unclear. Methods: This prospective cohort study was part of the European Network for the Investigation of Gender Incongruence. Serum levels of sex steroids were assessed in 746 AFAB transgender people during a 3-year follow-up period, starting at the initiation of hormone treatment. Results: Estradiol levels decreased from median [P25-P75] 45.6 [24.0-102.2] pg/mL to 36.5 [25.0-46.2] pg/mL over 3 years (p < 0.001); a change was already noticeable during the first 3 months (mean -17.1 pg/mL, 95% confidence interval -23.8 to -10.6, p < 0.001). Serum estradiol levels were lower in people without endogenous estradiol production from ovarian source (contraceptive users or post hystero-oophorectomy) at baseline and after 3 months, compared with people with endogenous estradiol production. Using long-acting testosterone undecanoate injections resulted in a more prominent decrease in serum estradiol values over 12 months, compared with short-acting mixed testosterone esters (p < 0.001) or testosterone gel (p = 0.001). Changes in serum estradiol were positively correlated to changes in luteinizing hormone (rho = 0.107, p < 0.001) and negatively correlated to changes in follicle-stimulating hormone levels (rho = -0.167, p < 0.001) and body mass index (rho = -0.082, p < 0.001). Conclusion: Testosterone administration in AFAB transgender people resulted in decreasing serum estradiol levels. Our results suggest that testosterone therapy leads to central suppression of estradiol production, with partial restitution due to aromatization

CBLL1 is hypomethylated and correlates with cortical thickness in transgender men before gender affirming hormone treatment

[Abstract] Gender identity refers to the consciousness of being a man, a woman or other condition. Although it is generally congruent with the sex assigned at birth, for some people it is not. If the incongruity is distressing, it is defined as gender dysphoria (GD). Here, we measured whole-genome DNA methylation by the Illumina © Infinium Human Methylation 850k array and reported its correlation with cortical thickness (CTh) in 22 transgender men (TM) experiencing GD versus 25 cisgender men (CM) and 28 cisgender women (CW). With respect to the methylation analysis, TM vs. CW showed significant differences in 35 CpGs, while 2155 CpGs were found when TM vs. CM were compared. With respect to correlation analysis, TM showed differences in methylation of CBLL1 and DLG1 genes that correlated with global and left hemisphere CTh. Both genes were hypomethylated in TM compared to the cisgender groups. Early onset TM showed a positive correlation between CBLL1 and several cortical regions in the frontal (left caudal middle frontal), temporal (right inferior temporal, left fusiform) and parietal cortices (left supramarginal and right paracentral). This is the first study relating CBLL1 methylation with CTh in transgender persons and supports a neurodevelopmental hypothesis of gender identity.Ministerio de Ciencia, Innovación y Universidades; PGC2018-094919-B-C21 & PDI21-127547NB-C21 (A.G.), PGC2018-094919-B-C22 and PID2021-127547NB-C22 (R.F., E.P.).Xunta de Galicia; ED431B 2022/16 (E.P.)Special Research Fund (BOF) of Ghent University (IOP003- 18) (S.M.C. and G.T.S)

Head-to-head comparison of two angiography-derived fractional flow reserve techniques in patients with high-risk acute coronary syndrome: A multicenter prospective study

BACKGROUND FFRangio and QFR are angiography-based technologies that have been validated in patients with stable coronary artery disease. No head-to-head comparison to invasive fractional flow reserve (FFR) has been reported to date in patients with acute coronary syndromes (ACS). METHODS This study is a subset of a larger prospective multicenter, single-arm study that involved patients diagnosed with high-risk ACS in whom 30-70% stenosis was evaluated by FFR. FFRangio and QFR - both calculated offline by 2 different and blinded operators - were calculated and compared to FFR. The two co-primary endpoints were the comparison of the Pearson correlation coefficient between FFRangio and QFR with FFR and the comparison of their inter-observer variability. RESULTS Among 134 high-risk ACS screened patients, 59 patients with 84 vessels underwent FFR measurements and were included in this study. The mean FFR value was 0.82 ± 0.40 with 32 (38%) being ≤0.80. The mean FFRangio was 0.82 ± 0.20 and the mean QFR was 0.82 ± 0.30, with 27 (32%) and 25 (29%) being ≤0.80, respectively. The Pearson correlation coefficient was significantly better for FFRangio compared to QFR, with R values of 0.76 and 0.61, respectively (p = 0.01). The inter-observer agreement was also significantly better for FFRangio compared to QFR (0.86 vs 0.79, p < 0.05). FFRangio had 91% sensitivity, 100% specificity, and 96.8% accuracy, while QFR exhibited 86.4% sensitivity, 98.4% specificity, and 93.7% accuracy. CONCLUSION In patients with high-risk ACS, FFRangio and QFR demonstrated excellent diagnostic performance. FFRangio seems to have better correlation to invasive FFR compared to QFR but further larger validation studies are required

Epigenetics Is Implicated in the Basis of Gender Incongruence: An Epigenome-Wide Association Analysis

[Abstract] Introduction: The main objective was to carry out a global DNA methylation analysis in a population with gender incongruence before gender-affirming hormone treatment (GAHT), in comparison to a cisgender population. Methods: A global CpG (cytosine-phosphate-guanine) methylation analysis was performed on blood from 16 transgender people before GAHT vs. 16 cisgender people using the Illumina© Infinium Human Methylation 850k BeadChip, after bisulfite conversion. Changes in the DNA methylome in cisgender vs. transgender populations were analyzed with the Partek® Genomics Suite program by a 2-way ANOVA test comparing populations by group and their sex assigned at birth. Results: The principal components analysis (PCA) showed that both populations (cis and trans) differ in the degree of global CpG methylation prior to GAHT. The 2-way ANOVA test showed 71,515 CpGs that passed the criterion FDR p < 0.05. Subsequently, in male assigned at birth population we found 87 CpGs that passed both criteria (FDR p < 0.05; fold change ≥ ± 2) of which 22 were located in islands. The most significant CpGs were related to genes: WDR45B, SLC6A20, NHLH1, PLEKHA5, UBALD1, SLC37A1, ARL6IP1, GRASP, and NCOA6. Regarding the female assigned at birth populations, we found 2 CpGs that passed both criteria (FDR p < 0.05; fold change ≥ ± 2), but none were located in islands. One of these CpGs, related to the MPPED2 gene, is shared by both, trans men and trans women. The enrichment analysis showed that these genes are involved in functions such as negative regulation of gene expression (GO:0010629), central nervous system development (GO:0007417), brain development (GO:0007420), ribonucleotide binding (GO:0032553), and RNA binding (GO:0003723), among others. Strengths and Limitations: It is the first time that a global CpG methylation analysis has been carried out in a population with gender incongruence before GAHT. A prospective study before/during GAHT would provide a better understanding of the influence of epigenetics in this process. Conclusion: The main finding of this study is that the cis and trans populations have different global CpG methylation profiles prior to GAHT. Therefore, our results suggest that epigenetics may be involved in the etiology of gender incongruence.Xunta de Galicia; ED431 B 019/02 (EP) Ministerio de Ciencia, Innovación y Universidades; PGC2018-094919-B-C21 (AG) e PGC2018-094919-B-C22 (RF and EP) Ghent University.; BOF interdisciplinary project (IOP003-18

Stellar Astrophysics and Exoplanet Science with the Maunakea Spectroscopic Explorer (MSE)

The Maunakea Spectroscopic Explorer (MSE) is a planned 11.25-m aperture facility with a 1.5 square degree field of view that will be fully dedicated to multi-object spectroscopy. A rebirth of the 3.6m Canada-France-Hawaii Telescope on Maunakea, MSE will use 4332 fibers operating at three different resolving powers (R ~ 2500, 6000, 40000) across a wavelength range of 0.36-1.8mum, with dynamical fiber positioning that allows fibers to match the exposure times of individual objects. MSE will enable spectroscopic surveys with unprecedented scale and sensitivity by collecting millions of spectra per year down to limiting magnitudes of g ~ 20-24 mag, with a nominal velocity precision of ~100 m/s in high-resolution mode. This white paper describes science cases for stellar astrophysics and exoplanet science using MSE, including the discovery and atmospheric characterization of exoplanets and substellar objects, stellar physics with star clusters, asteroseismology of solar-like oscillators and opacity-driven pulsators, studies of stellar rotation, activity, and multiplicity, as well as the chemical characterization of AGB and extremely metal-poor stars.Comment: 31 pages, 11 figures; To appear as a chapter for the Detailed Science Case of the Maunakea Spectroscopic Explore

Does root plasticity contribute to crop tolerance to abiotic stresses?

Poster that presents the experiments, the main results and take home messages