Gender dysphoria (GD) reflects distress caused by incongruence between one's experienced gender identity and one's natal (assigned) gender. Previous studies suggest that high levels of prenatal testosterone (T) in natal females and low levels in natal males might contribute to GD. Here, we investigated if the 2D:4D digit ratio, a biomarker of prenatal T effects, is related to GD. We first report results from a large Iranian sample, comparing 2D:4D in 104 transwomen and 89 transmen against controls of the same natal sex. We found significantly lower (less masculine) 2D:4D in transwomen compared to control men. We then conducted random-effects meta-analyses of relevant studies including our own (k = 6, N = 925 for transwomen and k = 6, N = 757 for transmen). In line with the hypothesized prenatal T effects, transwomen showed significantly feminized 2D:4D (d ≈ 0.24). Conversely, transmen showed masculinized 2D:4D (d ≈ − 0.28); however, large unaccounted heterogeneity across studies emerged, which makes this effect less meaningful. These findings support the idea that high levels of prenatal T in natal females and low levels in natal males play a part in the etiology of GD. As we discuss, this adds to the evidence demonstrating the convergent validity of 2D:4D as a marker of prenatal T effects.

With advances in bone tissue engineering, various materials and methods have been explored to find a better scaffold that can help in improving bone growth and regeneration. Three-dimensional (3D) printing by fused deposition modeling can produce customized scaffolds from biodegradable polyesters such as polycaprolactone (PCL). Although the fabricated PCL scaffolds exhibited a lack of bioactivity and poor cell attachment on their surfaces, herein, using a simple postfabrication modification method with hydroxyapatite (HA) and bioglasses (BGs), we obtained better cell proliferation and attachment. Biological behavior and osteosupportive capacity of the 3D-printed scaffolds including PCL, PCL/HA, PCL/BG, and PCL/HA/BG were evaluated in this study, while human adipose tissue-derived mesenchymal stem cells (hADSCs) were cultured on the scaffolds. The cell morphology, attachment, and proliferation were investigated using scanning electron microscopy (SEM), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, and 4′,6-diamidino-2-phenylindole (DAPI) staining. In the next step, the ability of stem cells to differentiate into osteoblasts was evaluated by measuring alkaline phosphatase (ALP) activity, calcium deposition, and bone-related gene and protein expression. In the end, the expression levels of miR-20a, miR-125a, and their target genes were also investigated as positive and negative regulators in osteogenesis pathways. The results showed that the coated scaffolds with bioceramics present a more appropriate surface for cell adhesion and proliferation, as well as efficient potential in inducing osteoconduction and osteointegration compared to PCL alone and control. The PCL/HA/BG scaffold exhibited higher in vitro cell viability and bone formation compared to the other groups, which can be due to the synergistic effect of HA and BG. On the whole, this tricomponent 3D-printing scaffold has a promising prospect for bone tissue engineering applications.

Self-healing and autologous bone graft of calvaraial defects can be challenging. Therefore, the fabrication of scaffolds for its rapid and effective repair is a promising field of research. This paper provided a comparative study on the ability of Three-dimensional (3D) printed polycaprolactone (PCL) scaffolds and PCL-modified with the hydroxyapatite (HA) and bioglasses (BG) bioceramics scaffolds in newly bone formed in calvaria defect area. The studied 3D-printed PCL scaffolds were fabricated by fused deposition layer-by-layer modeling. After the evaluation of cell adhesion on the surface of the scaffolds, they were implanted into a rat calvarial defect model. The rats were divided into four groups with scaffold graft including PCL, PCL/HA, PCL/BG, and PCL/HA/BG and a non-explant control group. The capacity of the 3D-printed scaffolds in calvarial bone regeneration was investigated using micro computed tomography scan, histological and immunohistochemistry analyses. Lastly, the expression levels of several bone related genes as well as the expression of miR-20a and miR-17-5p as positive regulators and miR-125a as a negative regulator in osteogenesis pathways were also investigated. The results of this comparative study have showed that PCL scaffolds with HA and BG bioceramics have a great range of potential applications in the field of calvaria defect treatment.