Fetal Programming Research Articles

Maternal nutrition and fetal imprinting of the male progeny

The global population as well as the demand for human food is rapidly growing worldwide, which necessitates improvement of efficiency in livestock operations. In this context, environmental factors during fetal and/or neonatal life have been observed to influence normal physical and physiological function of an individual during adulthood, and this phenomenon is called fetal or developmental programming. While numerous studies have reported the impact of maternal factors on development of the female progeny, limited information is available on the potential effects of fetal programming on reproductive function of the male offspring. Therefore, the objective for this review article was to focus on available literature regarding the impact of maternal factors, particularly maternal nutrition, on reproductive system of the male offspring. To this end, we highlighted developmental programming of the male offspring in domestic species (i.e., pig, cow and sheep) as well as laboratory species (i.e., mice and rat) during pregnancy and lactation. In this sense, we pointed out the effects of maternal nutrition on various functions of the male offspring including hypothalamic–pituitary axis, hormonal levels, testicular tissue and semen parameters.

Effect Of Prenatal Exercise Toward Clinical Outcome On Delivery Process At Permata Bunda Clinic, Serang In 2018

Prenatal exercise is one of activities in services during pregnancy. Prenatal exercise result in a better pregnancy product and better delivery outcome, compared to the mothers that do not follow prenatal exercise. Delivery is a physiological process. If the mother gets no clear information and do not examine her pregnancy regularly, it becomes pathological. The research aims to determine the effect of prenatal exercise toward clinical outcome in the delivery process at Permata Bunda clinic Serang 2018. The method used in the research was quasi Experimentt control group design. The samples were 20 pregnant mothers who follow prenatal exercise at Permata Bunda Clinic Serang. The result shows that prenatal exercise affect clinical outcome during the delivery process phase I,II,III,IV which is significant among experiment group (p = 0,000). Prenatal exercise could decrease pain and accelerate labor process. Permata Bunda Clinic needs to socialize the prenatal exercise program regularly.

Ментальне здоров’я вагітних: сучасні реалії

This review provides data on the impact of the war in Ukraine and the COVID-19 pandemic on the mental health of Ukrainian women during pregnancy, childbirth, and the postpartum period. It is noted that even in peacetime, the perinatal period is quite vulnerable. The aim of the study is to analyze the impact of post-traumatic stress disorder (PTSD) on the course of pregnancy, childbirth and the postpartum period. According to statistics, one in five women may have a perinatal mental disorder. In today's realities, mental health is given considerable attention. Mental health disorders, such as depression, anxiety and PTSD, manifested by negative thoughts, loss of interest and/or pleasure, fatigue and/or increased anxiety, are the most common diagnoses. It is clear that pregnancy and the postpartum period, although they can be joyful, are also times of stress and difficulty for mothers as they face physiological and psychosocial changes. Particular attention is paid to the connection of maternal depression and anxiety with an increase in inflammatory biomarkers in the mother during pregnancy, which is associated with an increased risk of neurodevelopment in children. Despite the contradictory results of the hypothesis about fetal programming, it is important to recognize that caring for the mother and the child are interconnected. Pregnant mothers who have PTSD are at increased risk of premature termination of pregnancy and premature birth, the development of preeclampsia, gestational diabetes, and other obstetric and perinatal losses. A review of the literature confirms the relevance of studying the impact of PTSD on the perinatal period, since timely diagnosis and treatment of mental disorders is a key element of preserving the health of pregnant women and ensuring the stable development of the nation. The authors declare no conflict of interest.

Prevalence of common autosomal recessive mutation carriers in women in the Southern Vietnam following the application of expanded carrier screening

The common autosomal recessive (AR) mutation carrier is still unknown in Vietnam. This study aims to identify the most common AR gene mutation carriers in women of reproductive age to build a Vietnamese-specific carrier screening panel for AR and X-linked disorders in the preconception and prenatal healthcare program. A cross-sectional study was conducted at University Medical Center–Branch 2 in Ho Chi Minh City from December 1st, 2020, to June 30th, 2023. 338 women have consented to take a 5 mL blood test to identify 540 recessive genes. The carrier screening panel was designed based on the American College of Medical Genetics and Genomics (ACMG)-recommended genes and suggestions from 104 clinical experts in Vietnam. Obstetricians and genetic experts counseled all positive testing results to discuss the possibility of recessive diseases in their offspring. The most common recessive disorders were defined at a prevalence of 1 in 60 or greater, and those were added to a Vietnamese-specific carrier screening panel. 338 non-pregnant and pregnant women underwent the expanded carrier screening (ECS). The carrier frequency was 63.6%, in which 215 women carried at least one AR gene mutation. GJB2 hearing impairment was identified as the most common chronic condition (1 in 5). The second most common AR disorder was beta-thalassemia (1 in 16), followed by cystic fibrosis (1 in 23), G6PD deficiency (1 in 28), Wilson’s disease (1 in 31), Usher’s syndrome (1 in 31), and glycogen storage disease (1 in 56). Seven common recessive genes were added in ethnic-based carrier screening. Women in the South of Vietnam have been carried for many recessive conditions at high frequency, such as hearing impairment, genetic anemia, and cystic fibrosis. It is necessary to implement a preconception and prenatal screening program by using seven widely popular AR genes in a Vietnamese-specific carrier screening panel to reduce the burden related to AR and X-linked disorders.

Substance P Concentration in Gestational Diabetes and Excessive Gestational Weight Gain and Its Impact on Neonatal Anthropometry.

Fetal programming is a process initiated by intrauterine conditions, leaving a lasting impact on the offspring's health, whether they manifest immediately or later in life. It is believed that children born to mothers with gestational diabetes mellitus (GDM) and excessive gestational weight gain (EGWG) may be at an increased risk of developing type 2 diabetes mellitus (T2DM) and obesity later in their adult lives. Substance P is a neurotransmitter associated with obesity development and impairment of insulin signaling. Dysregulation of substance P could lead to several pregnancy pathologies, such as preeclampsia and preterm birth. Our study aimed to compare substance P concentrations in serum and umbilical cord blood in patients with GDM, EGWG, and healthy women with a family history of gestational weight gain. Substance P levels in umbilical cord blood were significantly higher in the GDM group compared to the EGWG and control groups. Substance P levels in serum and umbilical cord blood were positively correlated in all groups and the GDM group. A very interesting direction for future research is the relationship between the concentration of substance P in newborns of diabetic mothers and the occurrence of respiratory distress syndrome as a complication of impaired surfactant synthesis. To our knowledge, it is the first study assessing substance P concentration in GDM and EGWG patients.

Aberrant stem cell and developmental programs in pediatric leukemia.

Hematopoiesis is a finely orchestrated process, whereby hematopoietic stem cells give rise to all mature blood cells. Crucially, they maintain the ability to self-renew and/or differentiate to replenish downstream progeny. This process starts at an embryonic stage and continues throughout the human lifespan. Blood cancers such as leukemia occur when normal hematopoiesis is disrupted, leading to uncontrolled proliferation and a block in differentiation of progenitors of a particular lineage (myeloid or lymphoid). Although normal stem cell programs are crucial for tissue homeostasis, these can be co-opted in many cancers, including leukemia. Myeloid or lymphoid leukemias often display stem cell-like properties that not only allow proliferation and survival of leukemic blasts but also enable them to escape treatments currently employed to treat patients. In addition, some leukemias, especially in children, have a fetal stem cell profile, which may reflect the developmental origins of the disease. Aberrant fetal stem cell programs necessary for leukemia maintenance are particularly attractive therapeutic targets. Understanding how hijacked stem cell programs lead to aberrant gene expression in place and time, and drive the biology of leukemia, will help us develop the best treatment strategies for patients.

ERRγ1 and Aromatase Expression in Human Placental Tissues from Term Deliveries of Large for Gestational Age Newborns

Plain Language SummaryEvents during fetal development are associated with susceptibility to chronic disease in adulthood. Extreme birth weight, for newborns of small for gestational age or large for gestational age (LGA), has been associated with an increased risk of developing metabolic syndrome in adulthood. Even though some intrauterine events during fetal development have been described, there is still a long way for identifying all the factors that are involved in fetal programming. The placenta has an important role in intrauterine programming because it controls the intrauterine environment by supplying oxygen, nutrients, and specific hormones involved in fetal development. Estrogens and androgens in maternal and fetal circulations play an important role in determining a physiological placental phenotype. ERRγ1 expression in placental tissues is involved in aromatase activity regulation and hence in intrauterine estrogen-androgen balance. In this study, we propose that the dysregulation of ERRγ1 in placental tissue might modify the estrogen-androgen balance in the intrauterine environment, representing one of the key factors in the regulation of fetal programming in LGA newborns.

Ultrasonographic Fetal Nuchal Translucency Measurements and Cytogenetic Outcomes

Ultrasonographic measurement of fetal nuchal translucency is used in prenatal screening for trisomies 21 and 18 and other conditions. A cutoff of 3.5 mm or greater is commonly used to offer follow-up investigations, such as prenatal cell-free DNA (cfDNA) screening or cytogenetic testing. Recent studies showed a possible association with chromosomal anomalies for levels less than 3.5 mm, but extant evidence has limitations. To evaluate the association between different nuchal translucency measurements and cytogenetic outcomes on a population level. This population-based retrospective cohort study used data from the Better Outcomes Registry & Network, the perinatal registry for Ontario, Canada. All singleton pregnancies with an estimated date of delivery from September 1, 2016, to March 31, 2021, were included. Data were analyzed from March 17 to August 14, 2023. Nuchal translucency measurements were identified through multiple-marker screening results. Chromosomal anomalies were identified through all Ontario laboratory-generated prenatal and postnatal cytogenetic tests. Cytogenetic testing results, supplemented with information from cfDNA screening and clinical examination at birth, were used to identify pregnancies without chromosomal anomalies. Multivariable modified Poisson regression with robust variance estimation and adjustment for gestational age was used to compare cytogenetic outcomes for pregnancies with varying nuchal translucency measurement categories and a reference group with nuchal translucency less than 2.0 mm. Of 414 268 pregnancies included in the study (mean [SD] maternal age at estimated delivery date, 31.5 [4.7] years), 359 807 (86.9%) had a nuchal translucency less than 2.0 mm; the prevalence of chromosomal anomalies in this group was 0.5%. An increased risk of chromosomal anomalies was associated with increasing nuchal translucency measurements, with an adjusted risk ratio (ARR) of 20.33 (95% CI, 17.58-23.52) and adjusted risk difference (ARD) of 9.94% (95% CI, 8.49%-11.39%) for pregnancies with measurements of 3.0 to less than 3.5 mm. The ARR was 4.97 (95% CI, 3.45-7.17) and the ARD was 1.40% (95% CI, 0.77%-2.04%) when restricted to chromosomal anomalies beyond the commonly screened aneuploidies (excluding trisomies 21, 18, and 13 and sex chromosome aneuploidies). In this cohort study of 414 268 singleton pregnancies, those with nuchal translucency measurements less than 2.0 mm were at the lowest risk of chromosomal anomalies. Risk increased with increasing measurements, including measurements less than 3.5 mm and anomalies not routinely screened by many prenatal genetic screening programs.

Incidence and Spectrum of Congenital Anomalies in Pediatric Populations of Southern Punjab, Pakistan

Background: Congenital anomalies (CAs) remain a significant concern for pediatric health worldwide, affecting millions of newborns. In Southern Punjab, Pakistan, a region characterized by its distinct socio-cultural dynamics, including a high prevalence of consanguineous marriages, the impact of these anomalies presents a unique public health challenge. This study aims to shed light on the incidence and spectrum of CAs within this context, exploring the genetic and environmental factors contributing to their prevalence.
 Objective: The primary objective of this study was to estimate the incidence and types of congenital anomalies among the pediatric population of Southern Punjab, with a particular focus on the relationship between consanguineous marriages and the prevalence of CAs.
 Methods: A cross-sectional study design was utilized, encompassing 406 pregnant women aged 20-42 from Southern Punjab, screened via ultrasound and genetic testing. The study emphasized the categorization of CAs across five main systems: digestive, central nervous, cardiovascular, ear-face-neck, and musculoskeletal. The inclusion of women with a history of cousin marriages provided a comparative analysis to understand the genetic impact on CA incidence.
 Results: Out of 406 newborns, a total of 16 (3.94%) were diagnosed with congenital anomalies. The distribution of CAs was as follows: digestive system (5 cases, 1.23%), central nervous system (3 cases, 0.74%), cardiovascular system (5 cases, 1.23%), anomalies of ear, face, and neck (3 cases, 0.74%), and musculoskeletal system (3 cases, 0.74%). Notably, the prevalence of CAs was higher in children born from cousin marriages (12 cases, 2.95%) compared to those from non-consanguineous unions (4 cases, 0.99%), with a statistically significant p-value of 0.05.
 Conclusion: The study underscores the heightened risk of congenital anomalies associated with consanguineous marriages in Southern Punjab, Pakistan. These findings advocate for enhanced genetic counseling and prenatal screening programs in regions with similar socio-cultural practices to mitigate the risks and impact of CAs.

Epigenetic modifications of placenta in women with gestational diabetes mellitus and their offspring.

Gestational diabetes mellitus (GDM) is a pregnancy-related complication characterized by abnormal glucose metabolism in pregnant women and has an important impact on fetal development. As a bridge between the mother and the fetus, the placenta has nutrient transport functions, endocrine functions, etc., and can regulate placental nutrient transport and fetal growth and development according to maternal metabolic status. Only by means of placental transmission can changes in maternal hyperglycemia affect the fetus. There are many reports on the placental pathophysiological changes associated with GDM, the impacts of GDM on the growth and development of offspring, and the prevalence of GDM in offspring after birth. Placental epigenetic changes in GDM are involved in the programming of fetal development and are involved in the pathogenesis of later chronic diseases. This paper summarizes the effects of changes in placental nutrient transport function and hormone secretion levels due to maternal hyperglycemia and hyperinsulinemia on the development of offspring as well as the participation of changes in placental epigenetic modifications due to maternal hyperglycemia in intrauterine fetal programming to promote a comprehensive understanding of the impacts of placental epigenetic modifications on the development of offspring from patients with GDM.

Maternal use of nitrosatable drugs during pregnancy and adult male reproductive health: A population-based cohort study.

Prenatal exposures to xenobiotics during the masculinization programming window are suggested to impact male fecundity later in life. Frequently used nitrosatable drugs, such as penicillins and beta2-agonists, contain amines or amides that may form teratogenic compounds in reaction with nitrite. We explored whether maternal nitrosatable drug use during gestation was associated with biomarkers of male fecundity in adulthood; moreover, the potential modifiable effect of nitrate and vitamin intake was investigated. We performed a cohort study in the Fetal Programming of Semen Quality cohort that includes semen characteristics, reproductive hormone concentrations, and measures of testis size on 1058 young adult sons in the Danish National Birth Cohort. Information on maternal use of nitrosatable drugs was obtained from questionnaires and interviews around gestational weeks 11 and 16. A multivariable negative binomial regression model was used to obtain relative differences in biomarkers of male fecundity for those whose mothers used nitrosatable drugs compared to those without such maternal use. In sub-analyses, the exposure was categorized according to nitrosatable drug type: secondary amine, tertiary amine, or amide. We investigated dose dependency by examining the number of weeks with intake and explored potential effect modification by low versus high maternal nitrate and vitamin intake from diet and nitrate concentration in drinking water. We added selection weights and imputed values of missing covariates to limit the risk of selection bias. In total, 19.6% of the study population were born of mothers with an intake of nitrosatable drugs at least once during early pregnancy. Relative differences in biomarkers related to male fecundity between exposed and unexposed participants were negligible. Imputation of missing covariates did not fundamentally alter the results. Furthermore, no sensitive subpopulations were detected. The results suggest that maternal use of nitrosatable drugs does not have a harmful influence on the male fecundity of the offspring.

Programming the next generation of prenatal programming of stress research: A review and suggestions for the future of the field.

In this article, I highlight core ideas, empirical findings, and advances in the study of how stress during pregnancy may prenatally program child neurodevelopmental, psychopathological, and health outcomes, emphasizing reviews, metanalyses, and recent contributions of conceptual and empirical work. The article offers a perspective on the history of this area of science, the underrecognized contributions of influential scholars from diverse fields of study, what we know from the evidence to date, the persistent challenges in sorting through what is left to learn, and suggestions for future research. I include sections focused on promoting resilience, pregnancy interventions that demonstrate positive effects across two generations, and the translational implications of the accruing data for practice and policy, highlighting opportunities for integrating across a range of fields and sectors. In the concluding sections, I discuss lessons learned from conducting this work and provide a closing summary of progress and future directions. The goal of this writing was to provide a viewpoint on some ways that emerging intergenerational transmission scholars might responsibly contribute to the future of the field of developmental psychopathology.

The Renin-Angiotensin System and Cardiovascular-Kidney-Metabolic Syndrome: Focus on Early-Life Programming.

The identification of pathological links among metabolic disorders, kidney ailments, and cardiovascular conditions has given rise to the concept of cardiovascular-kidney-metabolic (CKM) syndrome. Emerging prenatal risk factors seem to increase the likelihood of CKM syndrome across an individual's lifespan. The renin-angiotensin system (RAS) plays a crucial role in maternal-fetal health and maintaining homeostasis in cardiovascular, metabolic, and kidney functions. This review consolidates current preclinical evidence detailing how dysregulation of the RAS during pregnancy and lactation leads to CKM characteristics in offspring, elucidating the underlying mechanisms. The multi-organ effects of RAS, influencing fetal programming and triggering CKM traits in offspring, suggest it as a promising reprogramming strategy. Additionally, we present an overview of interventions targeting the RAS to prevent CKM traits. This comprehensive review of the potential role of the RAS in the early-life programming of CKM syndrome aims to expedite the clinical translation process, ultimately enhancing outcomes in cardiovascular-kidney-metabolic health.

Fetal Programming Influence on Microbiome Diversity and Ruminal and Cecal Epithelium in Beef Cattle.

We explored the influence of maternal nutritional strategies on the development of the rumen and cecum in offspring. Additionally, we investigated the potential repercussions of prenatal nutrition on the rumen and fecal microbiota composition, utilizing metagenomic 16S techniques, to understand the effects of fetal programming (FP) in Nellore cattle. A total of 63 bulls submitted to different prenatal nutrition strategies, namely, non-programming (NP), partial programming (PP), and complete programming (CP), were evaluated. The rumen epithelium was methodically evaluated based on the presence of rumenitis and structural irregularities. The assessment of cecum lesions was conducted post-evisceration, whereby all thoroughly cleaned ceca were methodically evaluated. Samples from 15 animals of rumen fluid at slaughter and feces during the finishing phase were collected, respectively. All DNA extraction were carried out using the Macherey Nagel NucleoSpin Tissue®, and 16S sequencing was conducted using the V4 primers on the MiSeq platform. Within the ruminal ecosystem, an estimated range of 90 to 130 distinct amplicon sequence variants was discerned, as distributed across 45,000 to 70,000 sequencing reads. Our metagenomic exploration unveils microbial communities that distinctly mirror gastrointestinal tract microenvironments and dietary influences. In sum, this comprehensive study advances our comprehension of FP, highlighting the interplay of maternal nutrition, gastrointestinal development, and microbial communities, contributing significantly to the fields of animal science.

Birth by caesarean section and semen quality in adulthood: a Danish population-based cohort study

BackgroundThe caesarean section (CS) rate has increased worldwide and there is an increasing public and scientific interest in the potential long-term health consequences for the offspring. CS is related to persistent aberrant microbiota colonization in the offspring, which may negatively interfere with sex hormone homeostasis and thus potentially affect the reproductive health. It remains unknown whether adult sons’ semen quality is affected by CS. We hypothesize that CS is associated with lower semen quality.MethodsThis study was based on the Fetal Programming of Semen Quality cohort (FEPOS, enrolled from 2017 to 2019) nested within the Danish National Birth Cohort (DNBC, enrolled from 1996 to 2002). A total of 5697 adult sons of mothers from the DNBC were invited to the FEPOS cohort, and 1044 young men participated in this study. Information on mode of delivery was extracted from the Danish Medical Birth Registry, and included vaginal delivery, elective CS before labor, emergency CS during labor and unspecified CS. The young men provided a semen sample for analysis of semen volume, sperm concentration, motility and morphology. Negative binomial regression models were applied to examine the association between CS and semen characteristics with estimation of relative differences in percentages with 95% confidence intervals (CIs).ResultsAmong included sons, 132 (13%) were born by CS. We found a slightly lower non-progressive sperm motility (reflecting higher progressive sperm motility) among sons born by CS compared to sons born by vaginal delivery [relative difference (95% CI): − 7.5% (− 14.1% to − 0.4%)]. No differences were observed for other sperm characteristics. When CS was further classified into elective CS, emergency CS and unspecified CS in a sensitivity analysis, no significant differences in non-progressive motility were observed among sons born by any of the three types of CS compared to sons born vaginally.ConclusionsThis large population-based cohort study found no significant evidence for an adverse effect on semen quality in adult sons born by CS.

Daily Injection of the β2 Adrenergic Agonist Clenbuterol Improved Muscle Glucose Metabolism, Glucose-Stimulated Insulin Secretion, and Hyperlipidemia in Juvenile Lambs Following Heat-Stress-Induced Intrauterine Growth Restriction.

Stress-induced fetal programming diminishes β2 adrenergic tone, which coincides with intrauterine growth restriction (IUGR) and lifelong metabolic dysfunction. We determined if stimulating β2 adrenergic activity in IUGR-born lambs would improve metabolic outcomes. IUGR lambs that received daily injections of saline or the β2 agonist clenbuterol from birth to 60 days were compared with controls from pair-fed thermoneutral pregnancies. As juveniles, IUGR lambs exhibited systemic inflammation and robust metabolic dysfunction, including greater (p < 0.05) circulating TNFα, IL-6, and non-esterified fatty acids, increased (p < 0.05) intramuscular glycogen, reduced (p < 0.05) circulating IGF-1, hindlimb blood flow, glucose-stimulated insulin secretion, and muscle glucose oxidation. Daily clenbuterol fully recovered (p < 0.05) circulating TNFα, IL-6, and non-esterified fatty acids, hindlimb blood flow, muscle glucose oxidation, and intramuscular glycogen. Glucose-stimulated insulin secretion was partially recovered (p < 0.05) in clenbuterol-treated IUGR lambs, but circulating IGF-1 was not improved. Circulating triglycerides and HDL cholesterol were elevated (p < 0.05) in clenbuterol-treated IUGR lambs, despite being normal in untreated IUGR lambs. We conclude that deficient β2 adrenergic regulation is a primary mechanism for several components of metabolic dysfunction in IUGR-born offspring and thus represents a potential therapeutic target for improving metabolic outcomes. Moreover, benefits from the β2 agonist were likely complemented by its suppression of IUGR-associated inflammation.

DHEA: a neglected biological signal that may affect fetal and child development.

The stress-sensitive maternal hypothalamic-pituitary-adrenal (HPA) axis through the end-product cortisol, represents a primary pathway through which maternal experience shapes fetal development with long-term consequences for child neurodevelopment. However, there is another HPA axis end-product that has been widely ignored in the study of human pregnancy. The synthesis and release of dehydroepiandosterone (DHEA) is similar to cortisol, so it is a plausible, but neglected, biological signal that may influence fetal neurodevelopment. DHEA also may interact with cortisol to determine developmental outcomes. Surprisingly, there is virtually nothing known about human fetal exposure to prenatal maternal DHEA and offspring neurodevelopment. The current study examined, for the first time, the joint impact of fetal exposure to prenatal maternal DHEA and cortisol on infant emotional reactivity. Participants were 124 mother-infant dyads. DHEA and cortisol were measured from maternal hair at 15 weeks (early gestation) and 35 weeks (late gestation). Observational assessments of positive and negative emotional reactivity were obtained in the laboratory when the infants were 6 months old. Pearson correlations were used to examine the associations between prenatal maternal cortisol, prenatal maternal DHEA, and infant positive and negative emotional reactivity. Moderation analyses were conducted to investigate whether DHEA might modify the association between cortisol and emotional reactivity. Higher levels of both early and late gestation maternal DHEA were linked to greater infant positive emotional reactivity. Elevated late gestation maternal cortisol was associated with greater negative emotional reactivity. Finally, the association between fetal cortisol exposure and infant emotional reactivity was only observed when DHEA was low. These new observations indicate that DHEA is a potential maternal biological signal involved in prenatal programming. It appears to act both independently and jointly with cortisol to determine a child's emotional reactivity. Its role as a primary end-product of the HPA axis, coupled with the newly documented associations with prenatal development shown here, strongly calls for the inclusion of DHEA in future investigations of fetal programming.

SOX17 enables immune evasion of early colorectal adenomas and cancers.

A hallmark of cancer is the avoidance of immune destruction. This process has been primarily investigated in locally advanced or metastatic cancer1-3; however, much less is known about how pre-malignant or early invasive tumours evade immune detection. Here, to understand this process in early colorectal cancers (CRCs), we investigated how naive colon cancer organoids that were engineered in vitro to harbour Apc-null, KrasG12D and Trp53-null (AKP) mutations adapted to the in vivo native colonic environment. Comprehensive transcriptomic and chromatin analyses revealed that the endoderm-specifying transcription factor SOX17 became strongly upregulated in vivo. Notably, whereas SOX17 loss did not affect AKP organoid propagation in vitro, its loss markedly reduced the ability of AKP tumours to persist in vivo. The small fraction of SOX17-null tumours that grew displayed notable interferon-γ (IFNγ)-producing effector-like CD8+ T cell infiltrates in contrast to the immune-suppressive microenvironment in wild-type counterparts. Mechanistically, in both endogenous Apc-null pre-malignant adenomas and transplanted organoid-derived AKP CRCs, SOX17 suppresses the ability of tumour cells to sense and respond to IFNγ, preventing anti-tumour T cell responses. Finally, SOX17 engages a fetal intestinal programme that drives differentiation away from LGR5+ tumour cells to produce immune-evasive LGR5- tumour cells with lower expression of major histocompatibility complex class I(MHC-I). We propose that SOX17 is a transcription factor that is engaged during the early steps of colon cancer to orchestrate an immune-evasive programme that permits CRC initiation and progression.

Application of DOHaD hypothesis to the Effect of Stress Levels in Pregnant Women on the Fetus and Baby’s Mental Health: A Literature Review

Introduction: According to the research of Cadzow et al., on antepartum and postpartum mental health, weak attachment bonding between the fetus and mother during pregnancy was associated with postpartum depression and anxiety. Sugishita et al. found that postpartum depression decreased when attachment to the fetus was higher during the antepartum period. Attachment to the fetus during pregnancy was associated with maternal mental health and was associated not only during pregnancy but with postpartum depression and blood cortisol levels, which are stress indicators, cross over the placenta and have been correlated with maternal and fetal levels. It has been afraied that strong psychological stress during pregnancy has some effect on the fetus and causes mental development in children, and the fetal programming hypothesis is pointed out in the background. However, there has been no previous research on the relationship between mental health such as stress in pregnant women and the fetal programming hypothesis. The purpose of this study is to examine the relationship between stress in pregnant women and the fetal programming hypothesis through literature. Methods: The databases used in the literature search are Pubmed, CINAHL, Cochrane Library, and Google Scholar. The search range is from 2000 to 2020. The criteria for adopting the document are 'DoHaD' x 'Mental Health', 'DoHaD' x 'Stress', and 'DoHaD' x 'Depression' in the English original article registered in the retrieved database. Among the retrieved articles, duplicate documents were excluded as a result of animal experiments and genome analysis. As a result, 13 articles were selected. Results &amp; Conclusion: As a result of conducting a literature review, it was found that when the stress of the pregnant woman is physically and psychologically high, the stress of the child is high. In particular, fetal dysfunction is likely to occur during labor if you spend pregnancy period when pregnancy complications and anxiety are strong. It is still necessary to examine the relationship between the child's growth and mental illness and the stress she received as a mother at the time of the fetus.

Nutritional Approaches Targeting Gut Microbiota in Oxidative-Stress-Associated Metabolic Syndrome: Focus on Early Life Programming.

Metabolic syndrome (MetS) denotes a constellation of risk factors associated with the development of cardiovascular disease, with its roots potentially traced back to early life. Given the pivotal role of oxidative stress and dysbiotic gut microbiota in MetS pathogenesis, comprehending their influence on MetS programming is crucial. Targeting these mechanisms during the early stages of life presents a promising avenue for preventing MetS later in life. This article begins by examining detrimental insults during early life that impact fetal programming, ultimately contributing to MetS in adulthood. Following that, we explore the role of oxidative stress and the dysregulation of gut microbiota in the initiation of MetS programming. The review also consolidates existing evidence on how gut-microbiota-targeted interventions can thwart oxidative-stress-associated MetS programming, encompassing approaches such as probiotics, prebiotics, postbiotics, and the modulation of bacterial metabolites. While animal studies demonstrate the favorable effects of gut-microbiota-targeted therapy in mitigating MetS programming, further clinical investigations are imperative to enhance our understanding of manipulating gut microbiota and oxidative stress for the prevention of MetS.