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Transcriptome and proteome dynamics of cervical remodeling in the mouse during pregnancy

ABSTRACT: Transcriptome and proteome dynamics of cervical remodeling in the mouse during pregnancy

PROVIDER: PRJNA688721 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13332106.fastq.gz	Fastqsanger.gz
	SRR13332107.fastq.gz	Fastqsanger.gz
	SRR13332108.fastq.gz	Fastqsanger.gz
	SRR13332109.fastq.gz	Fastqsanger.gz
	SRR13332110.fastq.gz	Fastqsanger.gz

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Transcriptome and proteome dynamics of cervical remodeling in the mouse during pregnancy

Project description:The transcriptomic patterns that drive cervical softening and ripening in early mid- and late pregnancy were identified in this study. Further we sought to evaluate protein turnover rates with a focus on ECM proteins. In early pregnancy there is a shift in immune cell and epithelial cell responses at the transcriptional level and an overall slowing down of protein turnover rates. By mid pregnancy transcriptomic patterns indicate there is an increase in extracellular matrix reorganization and by late pregnancy the transcriptional patterns of early and mid-pregnancy begin to reverse. Protein turnover rates for fibrillar collagen are high in the nonpregnant and pregnant cervix and thus allow for the rapid replacement of mature collagen with poorly crosslinked collagen through pregnancy.

2021-11-24 | GSE164059 | GEO

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Project description:The cervical epithelium undergoes continuous changes in proliferation, differentiation and function that is critical before pregnancy to ensure fertility and during pregnancy to provide a physical and immunoprotective barrier for pregnancy maintenance. Barrier disruption can lead to the ascension of pathogens that elicit inflammatory responses and preterm birth. Here we identify epithelial subtypes in the cervix of nonpregnant, pregnant and laboring mice using single cell- transcriptome and spatial analysis. We identify heterogeneous subpopulations of epithelia displaying spatial and temporal specificity in cell proliferation, turnover and transcriptional programs. Further we identify untimely proliferation and function of epithelial cells in a model of cervical epithelial barrier disruption. Together these data provide insights as to how the cervical epithelium undergoes a continuous remodeling to maintain a dynamically shifting state of homeostasis in pregnancy and labor and provide a framework by which to understand perturbations in epithelial cell health and host-microbe interactions that contribute to risk of premature birth.

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Transcriptome and proteome dynamics of cervical remodeling in the mouse during pregnancy†.

Project description:During gestation, the female reproductive tract must maintain pregnancy while concurrently preparing for parturition. Here, we explore the transitions in gene expression and protein turnover (fractional synthesis rates [FSR]) by which the cervix implements a transition from rigid to compliant. Shifts in gene transcription to achieve immune tolerance and alter epithelial cell programs begin in early pregnancy. Subsequently, in mid-to-late pregnancy transcriptional programs emerge that promote structural reorganization of the extracellular matrix (ECM). Stable isotope labeling revealed a striking slowdown of overall FSRs across the proteome on gestation day 6 that reverses in mid-to-late pregnancy. An exception was soluble fibrillar collagens and proteins of collagen assembly, which exhibit high turnover in nonpregnant cervix compared with other tissues and FSRs that continue throughout pregnancy. This finding provides a mechanism to explain how cross-linked collagen is replaced by newly synthesized, less cross-linked collagens, which allows increased tissue compliance during parturition. The rapid transition requires a reservoir of newly synthesized, less cross-linked collagens, which is assured by the high FSR of soluble collagens in the cervix. These findings suggest a previously unrecognized form of "metabolic flexibility" for ECM in the cervix that underlies rapid transformation in compliance to allow parturition.

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Cardiac Remodeling During Pregnancy With Metabolic Syndrome: Prologue of Pathological Remodeling

Project description:The heart undergoes physiological hypertrophy during pregnancy in healthy individuals. Metabolic syndrome (MetS) is now prevalent in women of child-bearing age and might add risks of adverse cardiovascular events during pregnancy. The present study asks if cardiac remodeling during pregnancy in obese individuals with MetS is abnormal and whether this predisposes them to a higher risk for cardiovascular disorders. The idea that MetS induces pathological cardiac remodeling during pregnancy was studied in a long-term (15 weeks) Western diet–feeding animal model that recapitulated features of human MetS. Pregnant female mice with Western diet (45% kcal fat)–induced MetS were compared with pregnant and nonpregnant females fed a control diet (10% kcal fat). Pregnant mice fed a Western diet had increased heart mass and exhibited key features of pathological hypertrophy, including fibrosis and upregulation of fetal genes associated with pathological hypertrophy. Hearts from pregnant animals with WD-induced MetS had a distinct gene expression profile that could underlie their pathological remodeling. Concurrently, pregnant female mice with MetS showed more severe cardiac hypertrophy and exacerbated cardiac dysfunction when challenged with angiotensin II/phenylephrine infusion after delivery. These results suggest that preexisting MetS could disrupt physiological hypertrophy during pregnancy to produce pathological cardiac remodeling that could predispose the heart to chronic disorders.

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Project description:The uterine cervix is the boundary structure between the uterus and the vagina and is a key component of the female reproductive tract for the maintenance of pregnancy and timing of parturition. Here we report on a comparative transcriptomic study of the cervix of four placental mammal species, mouse, guinea pig, rabbit and the basal eutherian mammal, armadillo, Dasypus novemcinctus, and one marsupial species, Monodelphis domestica. Our aim is to investigate the evolution of cervical gene expression as related to putative mechanisms for functional progesterone withdrawal. Our main findings are: 1) The patterns of gene expression found in eutherian species is consistent with the notion that an increase in the ratio of E/P4 signaling strength is critical for cervical remodeling. How the increased E/P4 ratio is achieved, however, is variable between eutherian species. 2) None of the genes related to steroid signaling modulated in eutherian species change expression during opossum gestation, suggesting that the role of P4 signaling in cervical remodeling evolved after the common ancestor of marsupials and placental mammals. 3) A tendency for decreased expression of progesterone receptor co-activators (NCOA1, -2 and -3, and CREBP) towards term is a shared derived feature of eutherians. This finding suggests that parturition is associated with broad scale histone de-acetylation. We tested this hypothesis by performing Western-blotting on mouse cervix and found evidence for a striking degree of histone de-acetylation in labor. This finding may have important implications for the control of premature cervical remodeling and preterm birth in humans.

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Cross breed RNASEQ analysis of cervical tissues in sheep

Project description:Aim to characterize the cervical transcriptome of four European ewe breeds with known differences in pregnancy rates following cervical AI using frozen-thawed semen.

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