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Effect of early postnatal stress on adult mouse Sertoli cells

ABSTRACT: Effect of early postnatal stress on adult mouse Sertoli cells

PROVIDER: PRJNA844395 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19511039.fastq.gz	Fastqsanger.gz
	SRR19511040.fastq.gz	Fastqsanger.gz
	SRR19511041.fastq.gz	Fastqsanger.gz
	SRR19511042.fastq.gz	Fastqsanger.gz
	SRR19511043.fastq.gz	Fastqsanger.gz

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Effect of early postnatal stress on adult mouse Sertoli cells

Project description:To investigate whether early postnatal stress has a long-lasting impact on Sertoli cells up to adulthood, we compared the gene expression of adult Sertoli cells obtained from stressed versus control mice.

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Project description:Early postnatal myofibroblasts are a key cell type involved in postnatal alveolarization. The majority of these cells undergo apoptosis post-alveolarization. However, some dedifferntaite and persist in the adult lung. We utilized single cell RNA seq. to understand transcriptomics of these persisted myofibroblasts.

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Long-term effects of early postnatal stress on Sertoli cells.

Project description:Sertoli cells are somatic cells in testis essential for spermatogenesis, that support the development, maturation, and differentiation of germ cells. Sertoli cells are metabolically highly active and physiologically regulated by external signals, particularly factors in the blood stream. In disease conditions, circulating pathological signals may affect Sertoli cells and consequentially, alter germ cells and fertility. While the effects of stress on reproductive cells have been well studied, how Sertoli cells respond to stress remains poorly characterized. We used a mouse model of early postnatal stress to assess the effects of stress on Sertoli cells. We developed an improved strategy based on intracellular stainings and obtained enriched preparations of Sertoli cells from exposed males. We show that adult Sertoli cells have impaired electron transport chain (ETC) pathways and that several components of ETC complexes particularly complex I, III, and IV are persistently affected. We identify serum as potential mediator of the effects of stress on Sertoli cells by showing that it can recapitulate ETC alterations in primary cells. These results highlight Sertoli cells as cellular targets of stress in early life that can keep a trace of exposure until adulthood.

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Pig liver postnatal vs adult proteome analysis

Project description:During the perinatal period, unique metabolic adaptations support energetic requirements for rapid growth. To gain insight into perinatal adaptations, quantitative proteomics were performed comparing the livers of yorkshire pigs at postnatal day seven and adult. These data revealed differences in the metabolic control of liver function including significant changes in lipid and carbohydrate metabolic pathways. Newborn livers showed an enrichment of proteins in lipid catabolism and gluconeogenesis concomitant with elevated liver carnitine and acylcarnitines levels. Sugar kinases were some of the most dramatically differentially enriched proteins comparing neonatal and adult pigs including galactokinase 1 (Galk1), ketohexokinase (KHK), hexokinase 1 (HK1) and hexokinase 4 (GCK). Interestingly, hexokinase domain containing 1 (HKDC1), an enigmatic fifth hexokinase associated with glucose disturbances in pregnant women was highly enriched in the liver during the prenatal and perinatal periods and continuously declined throughout postnatal development in pigs and mice. These changes were confirmed via Western blot and mRNA expression. These data provide new insights into the developmental and metabolic adaptations in the liver during the transition from the perinatal period to adulthood in multiple mammalian species.

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Proteomic consequences of early postnatal, chronic THC exposure for the adolescent and adult hippocampus

Project description:This study aims to identify the proteomic targets of THC in the early postnatal hippocampus of developing mice. Therefore, early postnatal C57Bl/6 mice (P5) were exposed daily and for 30 days to plant extracted THC (either 1 mg/kg or 5 mg/kg) or vehicle solution (saline with 3% Tween® 80) for the control group. All animals stayed with their mothers until P25 and after the initial drug exposure time (until P35) animals were given a drug-free resting period. The animals were sacrificed, and their hippocampus was dissected and prepared for the following proteomic analysis at either P48 or after an extended resting period at P120. We found 31 proteins to be changed after THC exposure compared to vehicle at P48 and 186 proteins showing modifications at P120. Gene ontology classification of protein targets revealed a substantial amount of proteins involved in metabolic processes of neurons after THC exposure. The results highlight the vulnerability of the developing hippocampus towards THC exposure and identify the mitochondrial as well as other cell metabolic processes as potential drug targets.

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Human Early Postnatal Thymus [CITE-seq]

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Project description:Germ cell neoplasia in situ (GCNIS) is the noninvasive precursor of testicular germ cell tumors type II (TGCT), the most common cancer in young men. GCNIS originates from embryonic germ cells blocked in their maturation. The causes are unknown. GCNIS is associated with impaired Sertoli cells that express fetal marker keratin 18 (KRT18) and pluripotency factor SOX2. According to the spread theory of the origin of GCNIS, these impaired Sertoli cells are prepubertal cells arrested in their maturation due to genetic anomalies and/ or environmental anti-androgens. Thus, they are unable to support the development of germ cells, leading to their maturational block with further progression into GCNIS. The alternative theory states that the impaired Sertoli cells are adult cells dedifferentiating secondarily due to the influence of GCNIS. To address this issue, we established a co-culture model of adult human Sertoli cells (FS1) and a seminoma cell line similar to GCNIS (TCam-2). After 2 weeks of co-culture, FS1 cells showed progressive expression of KRT18 and SOX2. Interestingly, TCam-2 cells in co-culture showed SOX2 expression and upregulation of further pluripotency- and reprogramming-associated genes (LEFTY1/2, GAL, DPPA5, NODAL, ZIC3, DND1, DPPA3, GDF3, BCAT1, JARID2, and DNMT3B), suggesting a seminoma to embryonal carcinoma transition. Thus, our FS1/ TCam-2 co-culture model is a valuable tool to investigate interactions between Sertoli cells and tumor cells. Our studies of human testicular biopsies with GCNIS further suggest that the impaired Sertoli cells associated to GCNIS represent adult cells undergoing progressive dedifferentiation.

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Polycomb suppresses a female gene regulatory network in Sertoli cells

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