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Abstract Background Pancreatic fibrosis is an early diagnostic feature of the common inherited disorder cystic fibrosis (CF). Many people with CF (pwCF) are pancreatic insufficient from birth and the replacement of acinar tissue with cystic lesions and fibrosis is a progressive phenotype that may later lead to diabetes. Little is known about the initiating events in the fibrotic process though it may be a sequela of inflammation in the pancreatic ducts resulting from loss of CFTR impairing normal fluid secretion. Here we use a sheep model of CF (CFTR −/− ) to examine the evolution of pancreatic disease through gestation. Methods Fetal pancreas was collected at six time points from 50-days of gestation through to term, which is equivalent to ~ 13 weeks to term in human. RNA was extracted from tissue for bulk RNA-seq and single cells were prepared from 80-day, 120-day and term samples for scRNA-seq. Data were validated by immunochemistry. Results Transcriptomic evidence from bulk RNA-seq showed alterations in the CFTR −/− pancreas by 65-days of gestation, which are accompanied by marked pathological changes by 80-days of gestation. These include a fibrotic response, confirmed by immunostaining for COL1A1, αSMA and SPARC, together with acinar loss. Moreover, using scRNA-seq we identify a unique cell population that is significantly overrepresented in the CFTR −/− animals at 80- and 120-days gestation, as are stellate cells at term. Conclusion The transcriptomic changes and cellular imbalance that we observe likely have pivotal roles in the evolution of CF pancreatic disease and may provide therapeutic opportunities to delay or prevent pancreatic destruction in CF.

Background: Pancreatic fibrosis is an early diagnostic feature of the common inherited disorder cystic fibrosis (CF). Many people with CF (pwCF) are pancreatic insufficient from birth and the replacement of acinar tissue with cystic lesions and fibrosis is a progressive phenotype that may later lead to diabetes. Little is known about the initiating events in the fibrotic process though it may be a sequela of inflammation in the pancreatic ducts resulting from loss of CFTR impairing normal fluid secretion. Here we use a sheep model of CF (CFTR−/−) to examine the evolution of pancreatic disease through gestation. Methods: Fetal pancreas was collected at six time points from 50-days of gestation through to term, which is equivalent to ~ 13 weeks to term in human. RNA was extracted from tissue for bulk RNA-seq and single cells were prepared from 80-day, 120-day and term samples for scRNA-seq. Data were validated by immunochemistry. Results: Transcriptomic evidence from bulk RNA-seq showed alterations in the CFTR−/− pancreas by 65-days of gestation, which are accompanied by marked pathological changes by 80-days of gestation. These include a fibrotic response, confirmed by immunostaining for COL1A1, αSMA and SPARC, together with acinar loss. Moreover, using scRNA-seq we identify a unique cell population that is significantly overrepresented in the CFTR−/− animals at 80- and 120-days gestation, as are stellate cells at term. Conclusion: The transcriptomic changes and cellular imbalance that we observe likely have pivotal roles in the evolution of CF pancreatic disease and may provide therapeutic opportunities to delay or prevent pancreatic destruction in CF. [ABSTRACT FROM AUTHOR]

The prenatal environment plays a critical role in shaping fetal development and ultimately the long-term health of the child. Here, we present data linking prenatal health, via maternal nutrition, comorbidities in pregnancy (e.g., diabetes, hypertension), and infectious and inflammatory exposures, to lifelong health through the developmental origins of disease framework. It is well-established that poor maternal health puts a child at risk for adverse outcomes in the first 1,000 days of life, yet the full health impact of the in utero environment is not confined to this narrow window. The developmental origins of disease framework identifies cognitive, neuropsychiatric, metabolic and cardiovascular disorders, and chronic diseases in childhood and adulthood that have their genesis in prenatal life. This perspective highlights the enormous public health implications for millions of pregnancies where maternal care, and therefore maternal health and fetal health, is lacking. Despite near universal agreement that access to antenatal care is a priority to protect the health of women and children in the first 1,000 days of life, insufficient progress has been achieved. Instead, in some regions there has been a political shift toward deprioritizing maternal health, which will further negatively impact the health and safety of pregnant people and their children across the lifespan. In this article we argue that the lifelong health impact attributed to the perinatal environment justifies policies aimed at improving access to comprehensive antenatal care globally.

Use of antidepressants (ADs) in general, and in pregnant notwithstanding, has been increasing globally in recent decades. Associations with a wide range of adverse perinatal and childhood outcomes following prenatal ADs exposure have been observed in registry-based studies, with Autism Spectrum Disorders (ASD) frequently reported. Studies using animal models, sibling analyses, and negative control approaches, have linked dysfunctional serotonin metabolism with ASD, but did not convincingly tease apart the role of maternal mental health from that of ADs. As work to decipher the nature of the AD-ASD association continues, this review raises some public health concerns pertinent to a hypothetical conclusion that this association is causal, including the need to identify specific gestation periods with higher risk, the importance of precise assessment of the ASD potential prevention that might be attributed to AD discontinuation, and the estimation of risks associated with prenatal exposure to untreated depression. [ABSTRACT FROM AUTHOR]

The gut microbiome is established in the newborn period and is recognised to interact with the host to influence metabolism. Different environmental factors that are encountered during this critical period may influence the gut microbial composition, potentially impacting upon later disease risk, such as asthma, metabolic disorder, and inflammatory bowel disease. The sterility dogma of the foetus in utero is challenged by studies that identified bacteria, bacterial DNA, or bacterial products in meconium, amniotic fluid, and the placenta; indicating the initiation of maternal-to-offspring microbial colonisation in utero. This narrative review aims to provide a better understanding of factors that affect the development of the gastrointestinal (GI) microbiome during prenatal, perinatal to postnatal life, and their reciprocal relationship with GI tract development in neonates. [ABSTRACT FROM AUTHOR]

The prenatal environment plays a critical role in shaping fetal development and ultimately the long-term health of the child. Here, we present data linking prenatal health, via maternal nutrition, comorbidities in pregnancy (e.g., diabetes, hypertension), and infectious and inflammatory exposures, to lifelong health through the developmental origins of disease framework. It is well-established that poor maternal health puts a child at risk for adverse outcomes in the first 1,000 days of life, yet the full health impact of the in utero environment is not confined to this narrow window. The developmental origins of disease framework identifies cognitive, neuropsychiatric, metabolic and cardiovascular disorders, and chronic diseases in childhood and adulthood that have their genesis in prenatal life. This perspective highlights the enormous public health implications for millions of pregnancies where maternal care, and therefore maternal health and fetal health, is lacking. Despite near universal agreement that access to antenatal care is a priority to protect the health of women and children in the first 1,000 days of life, insufficient progress has been achieved. Instead, in some regions there has been a political shift toward deprioritizing maternal health, which will further negatively impact the health and safety of pregnant people and their children across the lifespan. In this article we argue that the lifelong health impact attributed to the perinatal environment justifies policies aimed at improving access to comprehensive antenatal care globally., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 McDonald, Weckman, Wright, Conroy and Kain.)

This editorial aims to provide a concise summary of the factors involved in the dynamics of microbiome establishment and maturation. At the same time, it briefly updates the current knowledge and opens new questions in this regard. Many factors act as drivers of the microbiota's development at both pre- and post-natal levels (e.g., maternal factors, antibiotic usage, type of delivery, dietary pattern, post-natal feeding type, etc.). However, it is interesting to research into its real impact, the relationship between these external modulators, and how to modulate them. The are great opportunities for new research in the field. [ABSTRACT FROM AUTHOR]