ISSN 1662-4009 (online)

ey0017.15-11 | (1) | ESPEYB17

15.11. Targeting a ceramide double bond improves insulin resistance and hepatic steatosis

B Chaurasia , TS Tippetts , R Mayoral Monibas , J Liu , Y Li , L Wang , JL Wilkerson , CR Sweeney , RF Pereira , DH Sumida , JA Maschek , JE Cox , V Kaddai , GI Lancaster , MM Siddique , A Poss , M Pearson , S Satapati , H Zhou , DG McLaren , SF Previs , Y Chen , Y Qian , A Petrov , M Wu , X Shen , J Yao , CN Nunes , AD Howard , L Wang , MD Erion , J Rutter , WL Holland , DE Kelley , SA Summers

To read the full abstract: Science 2019;365:386–392.By genetically engineering mice, the authors deleted the enzyme dihydroceramide desaturase 1 (DES1), which normally inserts a conserved double bond into the backbone of ceramides. Ablation of DES1 from whole animals or tissue-specific deletion in the liver and/or adipose tissue resolved hepatic steatosis and insulin resistance in mice caused by leptin deficiency or obesogenic diets<p c...

ey0018.2-18 | Maternal Obesity and Long-term Infant Consequences | ESPEYB18

2.18. Maternal obesity interrupts the coordination of the unfolded protein response and heat shock response in the postnatal developing hypothalamus of male offspring in mice

N Chen , Y Zhang , M Wang , X Lin , J Li , J Li , X Xiao

Mol Cell Endocrinol. 2021 May 1;527:111218. doi: 10.1016/j.mce.2021.111218. PMID: 33636254This study used a high fat and high sucrose diet to generate obese mice. The offspring of these mice showed activation of the unfolding protein response and the heat-shock response in the hypothalamus as early as weaning. This was associated with malformed paraventricular nucleus axonal projections ...

ey0015.5-7 | Fractures, vitamin D and steroids – unclear associations | ESPEYB15

5.7 Vitamin D and Fracture Risk in Early Childhood: A Case-Control Study

LN Anderson , SW Heong , Y Chen , KE Thorpe , K Adeli , A Howard , E Sochett , CS Birken , PC Parkin , JL Maguire , TARGet Kids Collaboration

To read the full abstract: Am J Epidemiol 2017;185:1255-1262Vitamin D and adequate dietary calcium intake are important for skeletal health and therefore it was expected that vitamin D concentration would be associated with increased fracture risk. However, here, the authors did not find any statistically significant association between concurrent 25(OH)D concentration and fracture risk. In addition...

ey0019.6-7 | Basic and Genetic Research of DSD | ESPEYB19

6.7. MAP3K1 variant causes hyperactivation of Wnt4/[beta]-catenin/FOXL2 signaling contributing to 46,XY disorders/differences of sex development

H Chen , Q Chen , Y Zhu , K Yuan , H Li , B Zhang , Z Jia , H Zhou , M Fan , Y Qiu , Q Zhuang , Z Lei , M Li , W Huang , L Liang , Q Yan , C Wang

Front Genet. 2022 Mar 3;13:736988. PMID: 35309143, doi: 10.3389/fgene.2022.736988.Brief Summary: This molecular study highlights a novel mechanism of action of Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) in the development of testicular dysgenesis.MAP3K1 is one of the most common genes that has been identified to cause 46, XY DSD and variants are attribu...

ey0015.8-8 | Important for Clinical Practice | ESPEYB15

8.8 Noninvasive prenatal diagnosis of 21-hydroxylase deficiency using target capture sequencing of maternal plasma DNA

D Ma , Y Yuan , C Luo , Y Wang , T Jiang , F Guo , J Zhang , C Chen , Y Sun , J Cheng , P Hu , J Wang , H Yang , X Yi , W Wang , Asan , Z Xu

To read the full abstract: Sci Rep. 2017; 7(1): 7427Prenatal dexamethasone treatment has been suggested over three decades ago to prevent virilization of a female fetus affected with 21-hydroxylase deficiency due to genetic mutations in the CYP21A2 gene. However, current treatment guidelines for CAH regard this treatment still as experimental, mainly because follow-up studies of treated fetu...

ey0017.14-4 | (1) | ESPEYB17

14.4. Insights into human genetic variation and population history from 929 diverse genomes

A Bergstrom , SA McCarthy , R Hui , MA Almarri , Q Ayub , P Danecek , Y Chen , S Felkel , P Hallast , J Kamm , H Blanche , JF Deleuze , H Cann , S Mallick , D Reich , MS Sandhu , P Skoglund , A Scally , Y Xue , R Durbin , C Tyler-Smith

To read the full abstract: Science 2020; 367(6484):eaay5012.These authors sequenced 929 whole-genome sequences from 54 geographically, linguistically, and culturally diverse human populations, as part of the Human Genome Diversity Project, a panel of global populations. The data represent African, Oceanian, and American-Indian populations. They identified 67.3 million single-nucleotide polymorphisms (SNPs), 8.8 million small insertions or deleti...

ey0020.4-3 | Sexuality, Fertility and Fertility Optimization in DSD | ESPEYB20

4.3. AAV-mediated gene therapy produces fertile offspring in the Lhcgr-deficient mouse model of Leydig cell failure

K Xia , F Wang , X Lai , L Dong , P Luo , S Zhang , C Yang , H Chen , Y Ma , W Huang , W Ou , Y Li , X Feng , B Yang , C Liu , Z Lei , X Tu , Q Ke , FF Mao , C Deng , AP Xiang

Brief summary: In this in vivo study, Xia et al. demonstrate that AAV-mediated gene therapy recovers testosterone levels, restarts sexual development, restores spermatogenesis, and produces fertile offspring in a mouse model of Leydig cell failure (LCF).A null mutation in the gene encoding luteinizing hormone/choriogonadotrophin receptor (Lhcgr) causes a hereditary LCF in mice which is characterized by a reduction in testosterone levels...