Later Stages Of Gestation Research Articles

Melatonin Supplementation during the Late Gestational Stage Enhances Reproductive Performance of Sows by Regulating Fluid Shear Stress and Improving Placental Antioxidant Capacity

In this study, the effects of daily melatonin supplementation (2 mg/kg) at the late gestational stage on the reproductive performance of the sows have been investigated. This treatment potentially increased the litter size and birth survival rate and significantly increased the birth weight as well as the weaning weight and survival rate of piglets compared to the controls. The mechanistic studies have found that these beneficial effects of melatonin are not mediated by the alterations of reproductive hormones of estrogen and progesterone, nor did the glucose and lipid metabolisms, but they were the results of the reduced oxidative stress in placenta associated with melatonin supplementation. Indeed, the melatonergic system, including mRNAs and proteins of AANAT, MTNR1A and MTNR1B, has been identified in the placenta of the sows. The RNA sequencing of placental tissue and KEGG analysis showed that melatonin activated the placental tissue fluid shear stress pathway to stimulate the Nrf2 signaling pathway, which upregulated its several downstream antioxidant genes, including MGST1, GSTM3 and GSTA4, therefore, suppressing the placental oxidative stress. All these actions may be mediated by the melatonin receptor of MTNR1B.

Possible transfer of lncRNA H19-derived miRNA miR-675-3p to adjacent H19-non-expressing trophoblast cells in near-term mouse placenta.

LncRNA H19 serves as a regulatory RNA in mouse placental development. However, there is little information available on the in situ expression of H19 in the late-gestation mouse placenta. In this study, we performed quantitative polymerase chain reaction (qPCR) and in situ hybridization (ISH) analyses of lncRNA H19 and its exon 1-derived miRNA miR-675-3p to identify cell types expressing these non-coding RNAs in the mouse placenta during mid-to-late gestation. By qPCR analysis, we confirmed that H19 was highly expressed during mid-to-late gestation (E10.5-E18.5) and that H19-derived miRNA miR-675-3p was remarkably upregulated in the E18.5 placenta. ISH analysis revealed trophoblast cell type-specific expression of lncRNA H19 and miR-675-3p during later stages of gestation. In the junctional zone and decidua of late-gestation placenta, H19 was expressed in trophoblast giant cells and glycogen trophoblast cells; however, H19 was absent in spongiotrophoblast cells. In the labyrinth and chorionic plate, H19 was present in sinusoidal mononuclear trophoblast giant cells, fetal vascular endothelial cells, and basal chorionic trophoblast cells, but not in syncytiotrophoblasts. As expected, these lncRNA H19-expressing cells exhibited miR-675-3p in the E18.5 placenta. Intriguingly, miR-675-3p was also present in H19-negative spongiotrophoblast cells and syncytiotrophoblasts, implying the possible transfer of miR-675-3p from H19-exprssing cells to adjacent H19-non-expressing trophoblast cells. These findings suggest that the mouse placenta expresses lncRNA H19 in a trophoblast cell type-specific fashion during later stages of gestation.

Gestational bisphenol A exposure advances puberty onset in female offspring: Critical time window identification

Increasing evidence shows that the early onset of puberty in female offspring may be caused by maternal prenatal exposure to bisphenol A (BPA) during pregnancy; however, the critical time window of maternal prenatal BPA exposure remains unknown. Here, we identify the critical time window of gestational BPA exposure that induces early onset of puberty in female offspring. Pregnant CD-1 mice were gavaged with BPA (8 mg/kg) daily during the early gestational stage (GD1–GD6), middle gestational stage (GD7–GD12) or late gestational stage (GD13–GD18). We show that maternal BPA exposure during the early and middle gestational stages could advance the vaginal opening time and increase the serum levels of kisspeptin-10 and GnRH in the female offspring at PND 34. Mechanistically, maternal BPA exposure during early and middle gestation could significantly increase CpG island methylation in the Eed gene promoters but reduce the mRNA expression of Eed in the hypothalamus tissues of the female offspring. In conclusion, the critical period of maternal BPA exposure-induced early onset of puberty in female offspring is early and middle gestation; this BPA-induced early onset of puberty might be partly attributed to epigenetic programming of the Eed gene in the hypothalamus. This study provides important insights regarding the relationship and the mechanisms between BPA and offspring pubertal development.

Transcriptome Analysis of Goat Mammary Gland Tissue Reveals the Adaptive Strategies and Molecular Mechanisms of Lactation and Involution.

To understand how genes precisely regulate lactation physiological activity and the molecular genetic mechanisms underlying mammary gland involution, this study investigated the transcriptome characteristics of goat mammary gland tissues at the late gestation (LG), early lactation (EL), peak lactation (PL), late lactation (LL), dry period (DP), and involution (IN) stages. A total of 13,083 differentially expressed transcripts were identified by mutual comparison of mammary gland tissues at six developmental stages. Genes related to cell growth, apoptosis, immunity, nutrient transport, synthesis, and metabolism make adaptive transcriptional changes to meet the needs of mammary lactation. Notably, platelet derived growth factor receptor beta (PDGFRB) was screened as a hub gene of the mammary gland developmental network, which is highly expressed during the DP and IN. Overexpression of PDGFRB in vitro could slow down the G1/S phase arrest of goat mammary epithelial cell cycle and promote cell proliferation by regulating the PI3K/Akt signaling pathway. In addition, PDGFRB overexpression can also affect the expression of genes related to apoptosis, matrix metalloproteinase family, and vascular development, which is beneficial to the remodeling of mammary gland tissue during involution. These findings provide new insights into the molecular mechanisms involved in lactation and mammary gland involution.

Transplantation of Human-Fetal-Spinal-Cord-Derived NPCs Primed with a Polyglutamate-Conjugated Rho/Rock Inhibitor in Acute Spinal Cord Injury.

Neural precursor cell (NPC) transplantation represents a promising therapy for treating spinal cord injuries (SCIs); however, despite successful results obtained in preclinical models, the clinical translation of this approach remains challenging due, in part, to the lack of consensus on an optimal cell source for human neuronal cells. Depending on the cell source, additional limitations to NPC-based therapies include high tumorigenic potential, alongside poor graft survival and engraftment into host spinal tissue. We previously demonstrated that NPCs derived from rat fetal spinal cords primed with a polyglutamate (PGA)-conjugated form of the Rho/Rock inhibitor fasudil (PGA-SS-FAS) displayed enhanced neuronal differentiation and graft survival when compared to non-primed NPCs. We now conducted a similar study of human-fetal-spinal-cord-derived NPCs (hfNPCs) from legal gestational interruptions at the late gestational stage, at 19–21.6 weeks. In vitro, expanded hfNPCs retained neural features, multipotency, and self-renewal, which supported the development of a cell banking strategy. Before transplantation, we established a simple procedure to prime hfNPCs by overnight incubation with PGA-SS-FAS (at 50 μM FAS equiv.), which improved neuronal differentiation and overcame neurite-like retraction after lysophosphatidic-acid-induced Rho/Rock activation. The transplantation of primed hfNPCs into immune-deficient mice (NU(NCr)-Foxn1nu) immediately after the eighth thoracic segment compression prompted enhanced migration of grafted cells from the dorsal to the ventral spinal cord, increased preservation of GABAergic inhibitory Lbx1-expressing and glutamatergic excitatory Tlx3-expressing somatosensory interneurons, and elevated the numbers of preserved, c-Fos-expressing, activated neurons surrounding the injury epicenter, all in a low percentage. Overall, the priming procedure using PGA-SS-FAS could represent an alternative methodology to improve the capabilities of the hfNPC lines for a translational approach for acute SCI treatment.

Characterization of long noncoding RNA in nonlactating goat mammary glands reveals their regulatory role in mammary cell involution and remodeling

Long noncoding RNA (lncRNA) can regulate mammary gland development and lactation physiological activities. However, the molecular genetic mechanisms of lncRNA in mammary gland involution and cell remodeling remain unclear. This work analyzed the expression characteristics and molecular functions of lncRNA in goat mammary gland tissue at the late lactation (LL), dry period (DP), and late gestation (LG) stages. Sequencing results showed that 3074 lncRNAs were identified in non-lactating goat mammary gland tissue. Statistical analysis of lncRNA length characteristics and exon number found that goat lncRNAs were shorter in length, had fewer exons, and significantly lower expression levels than those of protein-coding genes. 331 differentially expressed lncRNAs were identified in the three comparison groups (LLvsDP, DPvsLG, and LLvsLG), which indicated that the lncRNAs expression at the transcriptional level were changed during mammary involution. Interestingly, lncRNAs were more actively expressed during the dry period compared to lactation, suggesting that lncRNAs in mammary glands are developmentally specific. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that lncRNAs could regulate immune function, cell proliferation, apoptosis, hormones, substance metabolism, transport, and intercellular communication in the mammary gland through various action modes. Among them, cis-acting lncRNAs enhanced the protection of mammary gland health during the dry period and late gestation. The above reflects the particular mechanisms of lncRNA to adapt to the developmental needs of mammary involution and remodeling. Furthermore, in the lncRNA-miRNA-mRNA network associated with mammary gland development, the expression of LOC102168552 was higher in late gestation than in the dry period and late lactation. Its expression was positively correlated with PRLR and negatively correlated with chi-miR-324-3p. Overexpression of LOC102168552 in goat mammary epithelial cells cultured in vitro could up-regulate PRLR to activate the prolactin signaling pathway by competitively binding to chi-miR-324-3p, promoting cell proliferation, reducing cell cycle arrest in the G1 / S phase, and inhibiting apoptosis. However, overexpression of LOC102168552 alone did not affect mammary cell growth status and the prolactin signaling pathway. This indicates that LOC102168552 must rely on chi-miR-324-3p to inhibit mammary cell apoptosis. In conclusion, the above analysis revealed that lncRNAs in goat mammary tissue are differentially expressed at different stages of involution. As expected, lncRNAs adaptively regulate various physiological activities during mammary gland involution through multiple modes of action, in preparation for a new round of lactation. These findings provide a reference and help further understand the regulatory role of lncRNAs in mammary cell involution and remodeling.

Dynamic regulation of lipid metabolism in the placenta of in vitro and in vivo models of gestational diabetes mellitus†.

The purpose of this study was to investigate lipid metabolism in the placenta of gestational diabetes mellitus individuals and to evaluate its effect on the fetus. We examined the expression of lipogenesis- and lipolysis-related proteins in the in vitro and in vivo gestational diabetes mellitus placenta models. The levels of sterol regulatory element binding protein-1c were increased, and fat accumulated more during early hyperglycemia, indicating that lipogenesis was stimulated. When hyperglycemia was further extended, lipolysis was activated due to the phosphorylation of hormone-sensitive lipase and expression of adipose triglyceride lipase. In the animal model of gestational diabetes mellitus and in the placenta of gestational diabetes mellitus patients during the extended stage of gestational diabetes mellitus, the expression of sterol regulatory element binding protein-1c decreased and the deposition of fat increased. Similar to the results obtained in the in vitro study, lipolysis was enhanced in the animal and human placenta of extended gestational diabetes mellitus. These results suggest that fat synthesis may be stimulated by lipogenesis in the placenta when the blood glucose level is high. Subsequently, the accumulated fat can be degraded by lipolysis and more fat and its metabolites can be delivered to the fetus when the gestational diabetes mellitus condition is extended at the late stage of gestation. Imbalanced fat metabolism in the placenta and fetus of gestational diabetes mellitus patients can cause metabolic complications in the fetus, including fetal macrosomia, obesity, and type 2 diabetes mellitus.

LRF Promotes Indirectly Advantageous Chromatin Conformation via BGLT3-lncRNA Expression and Switch from Fetal to Adult Hemoglobin.

The hemoglobin switch from fetal (HbF) to adult (HbA) has been studied intensively as an essential model for gene expression regulation, but also as a beneficial therapeutic approach for β-hemoglobinopathies, towards the objective of reactivating HbF. The transcription factor LRF (Leukemia/lymphoma-related), encoded from the ZBTB7A gene has been implicated in fetal hemoglobin silencing, though has a wide range of functions that have not been fully clarified. We thus established the LRF/ZBTB7A-overexpressing and ZBTB7A-knockdown K562 (human erythroleukemia cell line) clones to assess fetal vs. adult hemoglobin production pre- and post-induction. Transgenic K562 clones were further developed and studied under the influence of epigenetic chromatin regulators, such as DNA methyl transferase 3 (DNMT3) and Histone Deacetylase 1 (HDAC1), to evaluate LRF’s potential disturbance upon the aberrant epigenetic background and provide valuable information of the preferable epigenetic frame, in which LRF unfolds its action on the β-type globin’s expression. The ChIP-seq analysis demonstrated that LRF binds to γ-globin genes (HBG2/1) and apparently associates BCL11A for their silencing, but also during erythropoiesis induction, LRF binds the BGLT3 gene, promoting BGLT3-lncRNA production through the γ-δ intergenic region of β-type globin’s locus, triggering the transcriptional events from γ- to β-globin switch. Our findings are supported by an up-to-date looping model, which highlights chromatin alterations during erythropoiesis at late stages of gestation, to establish an “open” chromatin conformation across the γ-δ intergenic region and accomplish β-globin expression and hemoglobin switch.

Effects of Dietary Fiber, Crude Protein Level, and Gestation Stage on the Nitrogen Utilization of Multiparous Gestating Sows

Simple SummaryTwo major concerns for sustainable swine production are the shortage of protein feed resources and the excretion of nitrogen and phosphorus into the environment. Those concerns can be partly alleviated by increasing nitrogen utilization by improving nutrition for pigs. This study observed that a low crude protein and dietary fiber supplemented diet can improve nitrogen utilization and reduce urinary nitrogen excretion. Additionally, late gestating sows have greater nitrogen utilization than those of early gestation, characterized by reduced nitrogen in urine and lower amino acids in serum. These findings offer nutritional solutions for improving nitrogen utilization.To investigate the effects of dietary fiber (DF), crude protein (CP) level, and gestation stage on nitrogen utilization, 28 Landrace-Yorkshire cross gestating sows at parity two were randomly divided into four dietary treatments with seven duplicates of one pig with a repeated-measures design. The diets comprised one with normal crude protein (CP) of 13.3%, one with a low CP diet of 10.1%, and two diets, one with dietary fiber (DF) supplementation of inulin and cellulose at the ratio of 1:1 and one without DF. The total litter size, litter size alive, and newborn birthweight of piglets did not differ between treatment groups. Sows that received high DF levels had greater nitrogen output in feces, lower urinary nitrogen, and increased nitrogen retention. Sows that received a low CP diet had reduced nitrogen excretion in feces and urine, lower nitrogen retention, and an unchanged nitrogen retention ratio. Sows at the late stage of gestation on days 95 to 98 had lower nitrogen excretion in urine and greater nitrogen retention than in the early stage of gestation on days 35 to 38, associated with a significant decrease in serum amino acids in late gestation. Maternal protein deposition was increased by high DF, decreased by low CP, and lower in late gestation compared with early gestation. Collectively, DF improved nitrogen utilization by decreasing urine nitrogen output, and nitrogen utilization increased as gestation advanced.

Expression of FLRT2 in Postnatal Central Nervous System Development and After Spinal Cord Injury.

Fibronectin and leucine-rich transmembrane (FLRT) proteins are necessary for various developmental processes and in pathological conditions. FLRT2 acts as a homophilic cell adhesion molecule, a heterophilic repulsive ligand of Unc5/Netrin receptors, and a synaptogenic molecule; the last feature is mediated by binding to latrophilins. Although the function of FLRT2 in regulating cortical migration at the late gestation stage has been analyzed, little is known about the expression pattern of FLRT2 during postnatal central nervous system (CNS) development. In this study, we used Flrt2-LacZ knock-in (KI) mice to analyze FLRT2 expression during CNS development. At the early postnatal stage, FLRT2 expression was largely restricted to several regions of the striatum and deep layers of the cerebral cortex. In adulthood, FLRT2 expression was more prominent in the cerebral cortex, hippocampus, piriform cortex (PIR), nucleus of the lateral olfactory tract (NLOT), and ventral medial nucleus (VM) of the thalamus, but lower in the striatum. Notably, in the hippocampus, FLRT2 expression was confined to the CA1 region and partly localized on pre- and postsynapses whereas only few expression was observed in CA3 and dentate gyrus (DG). Finally, we observed temporally limited FLRT2 upregulation in reactive astrocytes around lesion sites 7 days after thoracic spinal cord injury. These dynamic changes in FLRT2 expression may enable multiple FLRT2 functions, including cell adhesion, repulsion, and synapse formation in different regions during CNS development and after spinal cord injury.

Violence and newborn health: Estimates for Colombia.

This paper examines the relationship between maternal exposure to violence during pregnancy and newborn birthweight. The identification strategy exploits variation in the timing of exposure and in the geographic location of expectant mothers across Colombian municipalities. Exposure to violence in early pregnancy had a large negative impact on birthweight, primarily for boys, and the effect was mitigated by their mothers' education. Girls' birthweight was affected mainly by shocks in later stages of gestation. Furthermore, their mothers were more likely to engage in potentially harmful behaviors during the pregnancy. This evidence exposes the importance of parental responses in shaping the effect of exposure to violence on newborn health.

Major Reorganization of Chromosome Conformation During Muscle Development in Pig

The spatial organization of the genome in the nucleus plays a crucial role in eukaryotic cell functions, yet little is known about chromatin structure variations during late fetal development in mammals. We performed in situ high-throughput chromosome conformation capture (Hi-C) sequencing of DNA from muscle samples of pig fetuses at two late stages of gestation. Comparative analysis of the resulting Hi-C interaction matrices between both groups showed widespread differences of different types. First, we discovered a complex landscape of stable and group-specific Topologically Associating Domains (TADs). Investigating the nuclear partition of the chromatin into transcriptionally active and inactive compartments, we observed a genome-wide fragmentation of these compartments between 90 and 110 days of gestation. Also, we identified and characterized the distribution of differential cis- and trans-pairwise interactions. In particular, trans-interactions at chromosome extremities revealed a mechanism of telomere clustering further confirmed by 3D Fluorescence in situ Hybridization (FISH). Altogether, we report major variations of the three-dimensional genome conformation during muscle development in pig, involving several levels of chromatin remodeling and structural regulation.

COVID-19 in pregnancy: placental pathological patterns and effect on perinatal outcome in five cases

IntroductionCOVID-19, the disease caused by the novel coronavirus SARS-CoV-2, is a severe systemic thrombotic syndrome that emerged in 2019, with an ensuing pandemic.To evaluate the impact of this disease on placental tissue and perinatal outcome, histological, immunohistochemical and ultrastructural analyses of placental tissue were performed for five cases of pregnant women with COVID-19.Case reportsAll five pregnant women in this series developed COVID-19 in late pregnancy. Two patients experienced respiratory distress, and computed tomography revealed signs of pneumonia, with bilateral involvement, multiple lobular and subsegmental areas of consolidation and ground-glass opacities.Histological studies of placental tissue revealed the presence of slight signs of maternal vascular underperfusion (MVUs) or foetal vascular underperfusion (FVUs) lesions and mild inflammatory lesions. CD15 immunoreactivity in the placental tissue was low in all cases, demonstrating that in these cases there was not severe foetal hypoxia/asphyxia risk for newborns or distal vascular immaturity.In all cases examined, ultrastructural analyses showed spherical-like coronavirus particles with an electron intermediate-density core as well as projections from the surface as spike-like structures in the syncytiotrophoblasts. At term, all of the women delivered newborns who were negative for SARS-CoV-2 by nasopharyngeal testing in their first day of life. All newborns were exclusively breastfed and were discharged on the 3rd day of life.ConclusionsIn conclusion, placental patterns in pregnancy due to COVID-19 in the late stage of gestation indicate no evidence of vertical trans-placental SARS-CoV-2 transmission or a significant impact on the perinatal outcome of newborns, in both mild and more severe cases.

The Programmed Cell Death Ligand-1/Programmed Cell Death-1 Pathway Mediates Pregnancy-Induced Analgesia via Regulating Spinal Inflammatory Cytokines.

BACKGROUND:The maternal pain threshold gradually increases during pregnancy, especially in late pregnancy. A series of mechanisms underlying pregnancy-induced analgesia have been reported. However, these mechanisms are still not completely clear, and the underlying molecular mechanisms need further investigation. We examined the relationship between the antinociceptive effect and the expression level of programmed cell death ligand-1 (PD-L1) during pregnancy and further observed the changes in pain thresholds and expression levels of cytokines in late-pregnant mice before and after blockade of PD-L1 or programmed cell death-1 (PD-1).METHODS:Part 1: Female mice were assigned to 3 groups (nonpregnant, late-pregnant, and postpartum). Part 2: Late-pregnant mice were assigned to 3 treatment groups (control [phosphate buffer solution], RMP1-14 [mouse anti–PD-1 antibody], and soluble PD-1 [sPD-1]). Behavioral testing (mechanical and thermal) and tissue (serum and spinal cord) analysis were performed on all groups. PD-L1, interleukin (IL)-10, tumor necrosis factor-α (TNF-α), and IL-6 expression levels in tissue were examined via reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blot analysis.RESULTS:The mechanical and thermal pain thresholds were significantly increased in late pregnancy and decreased after delivery. PD-L1 expression was also elevated in late pregnancy and decreased after delivery. In addition, in the late stage of gestation, the maternal inflammatory microenvironment was dominated by anti-inflammatory factors. After administration of RMP1-14 or sPD-1, the pain thresholds of late-pregnant mice were significantly reduced. In late-pregnant mice, the high level of IL-10 was obviously reduced, and the low levels of TNF-α and IL-6 were elevated.CONCLUSIONS:The PD-L1/PD-1 pathway mediates pregnancy-induced analgesia, partially via the regulation of cytokines.

Prenatal maternal depressive symptoms of Chinese pregnant women and twin newborns’ physical health: the moderating role of infant sex

ABSTRACT Consequences of prenatal maternal depressive symptoms on infant health are well established. But the results of infants’ sex differences of such consequences are mixed. The current study examines whether any association exists between prenatal maternal depressive symptoms and infant physical health different for the sex of newborns. A sample of 84 women pregnant with twins reported depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS) in the late gestational stage. The Apgar scores of newborns were assessed by healthcare providers at 1, 5, and 10 minutes after birth. The relationship of maternal prenatal depressive symptoms and newborns’ physical health was moderated by infant sex. Higher depressive symptoms were associated with a lower Apgar index among newborn boys but not girls. Fetus environment or biomarkers related to sex may be a key mechanism of the effect of prenatal depression symptoms on newborns’ health. Tailored interventions targeting maternal depression symptoms may be warranted.

Conversion of α-Cells to β-Cells in the Postpartum Mouse Pancreas Involves Lgr5 Progeny.

In contrast to the skin and the gut, where somatic stem cells and their niche are well characterized, a definitive pancreatic multipotent cell population in the adult pancreas has yet to be revealed. Of particular interest is whether such cells may be endogenous in patients with diabetes, and if so, can they be used for therapeutic purposes? In the current study, we used two separate reporter lines to target Cre-recombinase expression to the Lgr5- or glucagon-expressing cells in the pancreas. We provide evidence for the existence of a population of cells within and in the proximity of the ducts that transiently express the stem-cell marker Lgr5 during late gestational stages. Careful timing of tamoxifen treatment in Lgr5EGFP-IRES-CreERT2;R26Tomato mice allowed us to show that these Lgr5-expressing progenitor cells can differentiate into α-cells during pregnancy. Furthermore, we report on a spontaneous lineage conversion of α- to β-cells specifically after parturition. The contribution of Lgr5 progeny to the β-cell compartment through an α-cell intermediate phase early after pregnancy appears to be part of a novel mechanism that would counterbalance against excessive β-cell mass reduction during β-cell involution.

Altered sacral neural crest development in Pax3 spina bifida mutants underlies deficits of bladder innervation and function

Mouse models of Spina bifida (SB) have been instrumental for identifying genes, developmental processes, and environmental factors that influence neurulation and neural tube closure. Beyond the prominent neural tube defects, other aspects of the nervous system can be affected in SB with significant changes in essential bodily functions such as urination. SB patients frequently experience bladder dysfunction and SB fetuses exhibit reduced density of bladder nerves and smooth muscle although the developmental origins of these deficits have not been determined. The Pax3 Splotch-delayed (Pax3Sp-d) mouse model of SB is one of a very few mouse SB models that survives to late stages of gestation. Through analysis of Pax3Sp-d mutants we sought to define how altered bladder innervation in SB might arise by tracing sacral neural crest (NC) development, pelvic ganglia neuronal differentiation, and assessing bladder nerve fiber density. In Pax3Sp-d/Sp-d fetal mice we observed delayed migration of Sox10+ NC-derived progenitors (NCPs), deficient pelvic ganglia neurogenesis, and reduced density of bladder wall innervation. We further combined NC-specific deletion of Pax3 with the constitutive Pax3Sp-d allele in an effort to generate viable Pax3 mutants to examine later stages of bladder innervation and postnatal bladder function. Neural crest specific deletion of a Pax3 flox allele, using a Sox10-cre driver, in combination with a constitutive Pax3Sp-d mutation produced postnatal viable offspring that exhibited altered bladder function as well as reduced bladder wall innervation and altered connectivity between accessory ganglia at the bladder neck. Combined, the results show that Pax3 plays critical roles within sacral NC that are essential for initiation of neurogenesis and differentiation of autonomic neurons within pelvic ganglia.

Responses of Vaginal Microbiota to Dietary Supplementation with Lysozyme and its Relationship with Rectal Microbiota and Sow Performance from Late Gestation to Early Lactation.

Simple SummaryThe vaginal microbiota has a crucial role for the health of the sow and the newborn piglet. The purpose of this study was to investigate the effect of dietary supplementation with lysozyme in the vaginal microbiota and evaluate its relationship with the fecal microbiota of the rectum and the reproductive performance of the sow. The results suggest that, lysozyme supplementation changed vaginal microbiota composition at different taxonomic levels, the changed vaginal microbiota was associated with variations in fecal microbiota, and these changes correlated with some reproductive performance of the sow.This study was conducted to evaluate the effects of dietary lysozyme (LZM) supplementation on the vaginal microbiota, as well as the relationship between vaginal microbiota and the fecal microbiota of rectum and the reproductive performance of the sow. A total of 60 Yorkshire × Landrace sows (3–6 of parity) were arranged from day 85 of gestation to the end of lactation in a completely randomized design with three treatments (control diet, control diet + lysozyme 150 mg/kg, control diet + lysozyme 300 mg/kg). The results showed that sows fed with lysozyme increased serum interleukin-10 (IL-10, p < 0.05) on day 7 of lactation. The vaginal microbiota varied at different taxonomic levels with LZM supplementation by 16S rRNA gene sequencing. The most representative changes included a decrease in Tenericutes, Streptococcus, Bacillus and increase in Bacteroidetes, Actinobacteria, Enterococcus, and Lactobacillus (p < 0.05). There were 777 OTUs existing in both, vaginal and fecal microbiota. The addition of LZM also decreased the abundance of Tenericutes (p < 0.05) in the vagina and feces. The changes in the microbiota were correlated in some cases positively with the performance of the sow, for example, Bacillus in feces was positively correlated with the neonatal weight (p < 0.05). These results indicate that the addition of lysozyme to the diet of sow during perinatal period promote the change of vaginal bacterial community after farrowing. The variations in vaginal microbiota are also associated with the changes in the fecal microbiology of the rectum and the reproductive performance of the sow. Therefore, it is concluded that dietary supplementation with lysozyme in sows in late gestation stage until early lactation, is beneficial to establish vaginal microbiota that seems to promote maternal health and reproductive performance.

Effect of Chicken Extract on Breast Milk Production in Primiparous Mothers in Japan: A Randomized Clinical Trial

The purpose of this study was to assess the effects of chicken extract on breast milk production and fatigue in early postpartum women. The study is an open-label parallel-group randomized clinical trial involving 80 healthy primiparous women from Japan divided into two groups. The intervention group ingested chicken extract twice daily for more than two weeks and the control group ingested water. The effectiveness of chicken extract on breast milk production after delivery and quality of life before and after delivery was examined. The result showed that milk production in the chicken extract group (356±191mL) was higher than in the control group (279±142mL) at 96-120h, but not significantly different (P=0.071). Expressed milk production had increased significantly more at 96-120h in the chicken extract group (122.6±115.5mL) than in the control group (66.5±55.8mL) (P=0.017). Chicken extract significantly reduced fatigue at 38 weeks after gestation, as assessed by visual analog scale (P=0.006). The study concluded that milk production increased more in the intervention group. It is suggesting that the chicken extract may be effective in increasing breast milk production and reducing fatigue in later stage of gestation.

Diabetogenically beneficial gut microbiota alterations in third trimester of pregnancy.

SummaryAltered gut microbiota (dysbiosis), inflammation and weight gain are pivotal to the success of normal pregnancy. These are features of metabolic syndrome that ordinarily increase the risk of type 2 diabetes in non-pregnant individuals. Though gut microbiota influences host energy metabolism and homeostasis, the outcome (healthy or unhealthy) varies depending on pregnancy status. In a healthy pregnancy, the gut microbiota is altered to promote metabolic and immunological changes beneficial to the mother and foetus but could connote a disease state in non-pregnant individuals. During the later stages of gestation, metabolic syndrome-like features, that is, obesity-related gut dysbiotic microbiota, increased insulin resistance, and elevated pro-inflammatory cytokines, promote energy storage in adipose tissue for rapid foetal growth and development, and in preparation for energy-consuming processes such as parturition and lactation. The origin of this gestation-associated host–microbial interaction is still elusive. Therefore, this review critically examined the host–microbial interactions in the gastrointestinal tract of pregnant women at late gestation (third trimester) that shift host metabolism in favour of a diabetogenic or metabolic syndrome-like phenotype. Whether the diabetogenic effects of such interactions are indeed beneficial to both mother and foetus was also discussed with plausible mechanistic pathways and associations highlighted.Lay summaryIn non-pregnant women, increased blood glucose, fat accumulation, and prolonged immune response lead to obesity and diabetes. However, during the later stages of pregnancy, the changes in the body’s metabolism described previously do not lead to disease, instead pregnancy facilitates the storage of sufficient energy in fat cells for rapid growth and development of the foetus. The excess energy stores also prepares the mother for labour and breastfeeding. This review examines the role of the normal bacteria in the digestive tract in this beneficial energy accumulation and transfer between the mother and foetus without leading to obesity, diabetes and hypertension in pregnancy.