Expression of the Insulin-like Growth Factor system in first and second trimester human embryonic and fetal gonads

Financial Support: This work was supported by The Medical Research Council [MR/L010011/1 to PAF] and the European Community's Seventh Framework Programme (FP7/2007-2013) [under grant agreement no 212885 to PAF], BBSRC/EASTBIO (to AZ), ESHRE supported the ReproUnion fellowship (to AZ), Rigshospitalets Forskningspuljer (to LSM), and ReproUnion 1.0 (to LSM). Acknowledgement Marianne Sguazzino is acknowledged for excellent technical assistance. Gabriela Gudbergsen is acknowledged for her excellent design of Fig. 1. Data Availability: The dataset generated and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request. Microarray data are available with the Array Express accession number: E-MTAB-5611Peer reviewedPostprin

Real-Time Ultrasound/MRI Fusion for Suprasacral Parallel Shift Approach to Lumbosacral Plexus Blockade and Analysis of Injectate Spread:An Exploratory Randomized Controlled Trial

Fused real-time ultrasound and magnetic resonance imaging (MRI) may be used to improve the accuracy of advanced image guided procedures. However, its use in regional anesthesia is practically nonexistent. In this randomized controlled crossover trial, we aim to explore effectiveness, procedure-related outcomes, injectate spread analyzed by MRI, and safety of ultrasound/MRI fusion versus ultrasound guided Suprasacral Parallel Shift (SSPS) technique for lumbosacral plexus blockade. Twenty-six healthy subjects aged 21–36 years received two SSPS blocks (20 mL 2% lidocaine-epinephrine [1 : 200,000] added 1 mL diluted contrast) guided by ultrasound/MRI fusion versus ultrasound. Number (proportion) of subjects with motor blockade of the femoral and obturator nerves and the lumbosacral trunk was equal (ultrasound/MRI, 23/26 [88%]; ultrasound, 23/26 [88%]; p=1.00). Median (interquartile range) preparation and procedure times (s) were longer for the ultrasound/MRI fusion guided technique (686 [552–1023] versus 196 [167–228], p<0.001 and 333 [254–439] versus 216 [176–294], p=0.001). Both techniques produced perineural spread and corresponding sensory analgesia from L2 to S1. Epidural spread and lidocaine pharmacokinetics were similar. Different compartmentalized patterns of injectate spread were observed. Ultrasound/MRI fusion guided SSPS was equally effective and safe but required prolonged time, compared to ultrasound guided SSPS. This trial is registered with EudraCT (2013-004013-41) and ClinicalTrials.gov (NCT02593370)

Hallmarks of Human Small Antral Follicle Development: Implications for Regulation of Ovarian Steroidogenesis and Selection of the Dominant Follicle

Regulation of human ovarian steroidogenesis differs from other species and precise knowledge on how human small antral follicles (hSAF) develop and acquire competence for continued growth and steroid output is still incomplete. The present study has characterized almost 1,000 normal hSAF collected in connection with cryopreservation of ovarian tissue for fertility preservation. The antral follicles (ranging from 3 to 13 mm) were generally aspirated from one ovary surgically removed during the natural cycle, and the follicular fluid (FF) and the granulosa cells (GC) were isolated and snap-frozen. In FF, the following hormones were measured: inhibin-B, inhibin-A, AMH, follistatin, PAPP-A, estradiol, progesterone, testosterone, and androstenedione. In GC, mRNA gene expressions using q-PCR were measured for the following genes: FSHR, AMH, CYP19, and AR. All samples in which one of the abovementioned parameters was measured were included, but typically multiple parameters were measured. Highly significant differences in concentration and follicular content in relation to follicular diameter were found for all measured hormones despite massive variability in-between follicles for any given diameter. The results demonstrate that profound changes take place in the hormonal microenvironment around follicular diameters of 8–11 mm corresponding to when follicular selection occurs. At this point, inhibin-B and inhibin-A showed distinct peaks concomitant with a significant reduction in both AMH protein and mRNA expression. Concentrations of inhibins, androgens, FSHR, and AR were intimately associated, and it is suggested that inhibin-B in combination with PAPP-A and thereby IGF2 activity exerts important paracrine signaling at follicular selection. At the same time upregulation of estradiol synthesis and CYP19 mRNA expression increased steroid output profoundly. Furthermore, the highly significant association between FSHR and AR mRNA gene expression enforces important functions of androgens in follicular development. Collectively, these data reintroduce the understanding of the follicular phase as two parted in which regulation of steroidogenesis differs. The profound changes taking place around follicular selection highlight important paracrine actions of TGF-β family members and IGFs for securing dominance of the selected follicle