• Gillespie Mcgee posted an update 6 hours, 15 minutes ago

    Over the entire reproductive lifespan in mammals, a fixed number of primordial follicles serve as the source of mature oocytes. Uncontrolled and excessive activation of primordial follicles can lead to depletion of the ovarian reserve. We observed that disruption of ESR2-signaling results in increased activation of primordial follicles in Esr2-null (Esr2-/-) rats. However, follicle assembly was unaffected, and the total number of follicles remained comparable between neonatal wildtype and Esr2-/- ovaries. While the activated follicle counts were increased in Esr2-/- ovary, the number of primordial follicles were markedly decreased. Excessive recruitment of primordial follicles led to premature ovarian senescence in Esr2-/- rats and was associated with reduced levels of serum AMH and estradiol. Disruption of ESR2-signaling through administration of a selective antagonist (PHTPP) increased the number of activated follicles in wildtype rats, whereas a selective agonist (DPN) decreased follicle activation. In contrast, primordial follicle activation was not increased in the absence of ESR1 indicating that the regulation of primordial follicle activation is ESR2-specific. Follicle activation was also increased in Esr2-mutants lacking the DNA-binding domain, suggesting a role for the canonical transcriptional activation function. Both primordial and activated follicles express ESR2 suggesting a direct regulatory role for ESR2 within these follicles. We also detected that loss of ESR2 augmented the activation of AKT, ERK and mTOR pathways. Our results indicate that the lack of ESR2 upregulated both granulosa and oocyte factors, which can facilitate AKT and mTOR activation in Esr2-/- ovaries leading to increased activation of primordial follicles. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.BACKGROUND Pigs were domesticated independently from European and Asian wild boars nearly 10,000 years ago. Chinese indigenous pigs have been historically introduced to improve Europe local pigs. However, the geographic origin and biological functions of introgressed Chinese genes in modern European pig breeds remain largely unknown. RESULTS Here we explored whole-genome sequencing data from 266 Eurasian wild boars and domestic pigs to produce a fine-scale map of introgression between French Large White (FLW) and Chinese pigs. We show that FLW pigs had historical admixture with both Southern Chinese (SCN) and Eastern Chinese (ECN) pigs ∼200-300 years ago. Moreover, a set of SCN haplotypes was shown to be beneficial for improving disease resistance and ECN haplotypes are favorable for improved reproductive performance in FLW pigs. selleckchem In addition, we confirm human-mediated introgression events at the AHR locus, at which the haplotype of most likely ECN origin contributes to increased fertility of FLW pigs. CONCLUSIONS This study advances our understanding of the breeding history of global domestic pigs and highlights the importance of artificial introgression in the formation of phenotypic characteristics in domestic animals. © The Author(s) 2020. Published by Oxford University Press.BACKGROUND The loquat (Eriobotrya japonica) is a species of flowering plant in the family Rosaceae that is widely cultivated in Asian, European, and African countries. It blossoms in the winter and ripens in the early summer. The genome of loquat has to date not been published, which limits the study of molecular biology in this cultivated species. Here, we used the third-generation sequencing technology of Nanopore and Hi-C technology to sequence the genome of Eriobotrya. FINDINGS We generated 100.10 Gb of long reads using Oxford Nanopore sequencing technologies. Three types of Illumina high-throughput sequencing data, including genome short reads (47.42 Gb), transcriptome short reads (11.06 Gb), and Hi-C short reads (67.25 Gb), were also generated to help construct the loquat genome. All data were assembled into a 760.1-Mb genome assembly. The contigs were mapped to chromosomes by using Hi-C technology based on the contacts between contigs, and then a genome was assembled exhibiting 17 chromosomes and a scaffold N50 length of 39.7 Mb. A total of 45,743 protein-coding genes were annotated in the Eriobotrya genome, and we investigated the phylogenetic relationships between the Eriobotrya and 6 other Rosaceae species. Eriobotrya shows a close relationship with Malus and Pyrus, with the divergence time of Eriobotrya and Malus being 6.76 million years ago. Furthermore, chromosome rearrangement was found in Eriobotrya and Malus. CONCLUSIONS We constructed the first high-quality chromosome-level Eriobotrya genome using Illumina, Nanopore, and Hi-C technologies. This work provides a valuable reference genome for molecular studies of the loquat and provides new insight into chromosome evolution in this species. © The Author(s) 2020. Published by Oxford University Press.BACKGROUND Despite its high prevalence and health burden, many aspects of endometriosis remain unclear, including risk factors and the underlying biological mechanisms. Exposures during early life, including in utero, are thought to play an important role in the subsequent onset of the condition. To date, however, much of the evidence from studies on early life exposures and diagnosed endometriosis appears mixed and difficult to assess. OBJECTIVE AND RATIONALE This study aims to provide a systematic review of the epidemiologic evidence on early life factors associated with the subsequent diagnosis of endometriosis. In utero and early life exposures have previously been linked to a range of adult health outcomes, including infertility. SEARCH METHODS A systematic review of case-control, cross-sectional and cohort studies was conducted using the search terms ‘endometriosis'[MeSH] AND (‘risk factors'[MeSH] OR ‘protective factors'[MeSH]) AND (‘in utero’, ‘fetal’, ‘neonatal, ‘perinatal’, ‘developmental origins’, ‘ Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail journals.permission@oup.com.Background O6-methylguanine-DNA methyltransferase (MGMT) is a specific DNA damage reversal repair protein. The influence of MGMT status on alkylating agent sensitivity in patients with neuroendocrine neoplasms (NENs) is controversial. We conducted a meta-analysis to assess the influence of MGMT status on the therapeutic sensitivity of alkylating agents in patients with NENs. Methods We searched PubMed, EmBase, and Cochrane library public databases through 3 July 2019. The objective response rate (ORR) was the outcome data of interest. Subgroup analysis was performed according based on MGMT methylation and expression of MGMT protein. Results Eleven studies were included in the meta-analysis. The proportion of patients with NENs that achieved an ORR after alkylating agent treatment was higher in the MGMT-deficient group than the non-deficient group (OR 5.00; 95% CI 3.04-8.22; p less then 0.001; I2 3%). Similar results were noted in the MGMT methylation and MGMT protein expression subgroups. Conclusion Patients with NENs and MGMT methylation or low protein expression had a higher ORR proportion than patients without MGMT methylation or high protein expression.