No description available.

The fetal component of the human placenta is comprised of cells termed trophoblasts and the proper differentiation of these cells is pivotal for maintaining maternal and fetal health throughout pregnancy. The placental syncytiotrophoblast layer is a key secretory portion of the placenta and is produced through fusion of underlying progenitor cytotrophoblast cells with the multinucleated syncytiotrophoblast layer. The MacPhee laboratory has previously established that fusion or syncytialization of cytotrophoblasts is aided by expression of integrin-linked kinase (ILK), a cytoplasmic adapter protein. Nuclear enzyme Poly ADP-ribose Polymerase-1 (PARP-1) and the transcriptional repressor Snail-1 work with ILK to downregulate epithelial cell-cell adhesion. This process would also be necessary for proper trophoblast syncytialization. Thus, it was hypothesized that PARP-1 would be an important mediator of syncytiotrophoblast development. To test this hypothesis, immunofluorescence analysis of PARP-1 and Snail expression in human chorionic villi from first and second trimester as well as from term pregnancy was conducted. Furthermore, co-localization between PARP-1 and Snail-1 were evaluated. Lastly, human PARP-1 was overexpressed in the BeWo trophoblast derived cell line, under fusion promoting conditions, to directly test the ability of PARP-1 to regulate trophoblast fusion. Throughout the first and second trimester, PARP-1 and Snail were highly expressed and co-localized in villous cytotrophoblast nuclei. In contrast, PARP-1 was rarely detectable in syncytiotrophoblast nuclei, while Snail was highly expressed. Upon transient overexpression of PARP-1 in BeWo cells, fusion was robustly promoted. Furthermore, the mean number of nuclei per syncytium was markedly higher in PARP-overexpressing cells compared to control cells. However, PARP-1 overexpression did not regulate trophoblast hormonal differentiation. In conclusion, PARP-1 does appear to be a key enzyme in the process of trophoblast syncytialization. Lastly, a comparative analysis of PARP-1 was conducted in the mouse placenta. It was found that PARP-1 was highly detectable in nuclei of mononuclear trophoblast as well as the nuclei in the syncytiotrophoblast bilayer of the mouse labyrinth. Additionally, PARP-1 was localized to the nuclei of other trophoblast populations, including spongiotrophoblasts, trophoblast giant cell, and glycogen trophoblast giant cells, which are involved in the invasive pathway of trophoblast differentiation.

Understanding the physiology of pregnancy enables effective management of pregnancy complications that could otherwise be life threatening for both mother and fetus. A functional uterus (a) retains the fetus in utero during pregnancy without initiating stretch-induced contractions and (b) is able to dilate the cervix and contract the myometrium at term to deliver the fetus. The onset of labour is associated with successful cervical remodelling and contraction of myometrium, arising from concomitant activation of uterine immune and endocrine systems. A large body of evidence suggest that the action of local sex hormones may drive changes occurring in the uterine microenvironment at term. Although there have been a number of studies considering the potential role(s) played by progesterone and estrogens at the time of parturition, the role of androgens has received less scrutiny. The overarching aim of this thesis was to investigate the potential roles of androgens in myometrial biology at the time of pregnancy. We examined both the genetranscription dependent (genomic) and independent (non-genomic) action of androgens on the uterine smooth muscle, employing in vitro, ex vivo, and in vivo approaches. We found that the androgen receptor (AR) mRNA was significantly increased in the myometrium during labour when compared to the term non-labouring myometrium. Our gene expression studies revealed that ligand-dependent AR signalling in the myometrium might play a role in regulation of uterine smooth muscle cell contractility. We explored the effect of androgens on contraction of uterine smooth muscle strips obtained from both human myometrial biopsies collected at term and murine uterine horns. We found that testosterone (T) and dihydrotestosterone (DHT) in a range of 10-100 μM concentrations rapidly relaxed spontaneous and oxytocin-initiated contractions. The relaxant effect was not mediated by the classical intracellular AR nor was cell-surface initiated as shown by experiments employing a specific AR antagonist (flutamide) and a cell-surface impermeable androgen (TBSA). We investigated whether the relaxant effect was specific to androgens or a generic effect of sex hormones. We demonstrated that both estradiol (E2) and progesterone (P4) were also capable of relaxing the human and murine myometrium at the same dose range. In addition, a sex hormone “cocktail” (all four sex hormones combined at 10 μM dose each) mimicked the relaxant effect that each individual sex hormone elicited at a 40 μM dose, implying that the effect was possibly attributable to the steroid structure of the sex hormones. To study the underlying molecular events that mediate the relaxant effect of sex hormones observed ex vivo, we employed two human myometrial cell lines namely PHM1-41s and UtSMCs. We demonstrated that the androgen-induced relaxation in vitro was not induced by cell death but was mediated by a physiological mechanism whereby incubation with the androgen impaired the stimulated-Ca2+ entry into the uterine myocytes, which in turn resulted in poor phosphorylation of myosin light chain protein. Finally, we conducted a pilot study to explore the hypothesis that administration of androgen could relax the uterine muscle in vivo. We utilised a mouse model of infection-induced preterm labour, where infection was induced by intrauterine administration of liposaccharide (LPS) on day 17 of murine pregnancy. Our preliminary data showed that intrauterine administration of DHT on day 17 did not significantly reduce the rate of LPS-induced preterm birth in the doses tested in this study. In conclusion, the androgen-induced in vitro tocolysis appears to be sex hormone-specific rather than androgen-specific. Therefore, sex hormones might have the potential to be used for effective in vivo tocolysis to inhibit premature-initiated contractions. Our investigation of the androgen-dependent signalling in the myometrium contributed to the development of novel hypotheses regarding the role of androgens in the regulation of the phenotypic transition of MSMCs during pregnancy. These hypotheses remain to be confirmed in future studies.

Recent progress in science and medicine is that regions such as the United States, Canada, Australia, and Western Europe have witnessed dramatic declines in infant morbidity and mortality. The most significant of these declines has occurred among infants born prematurely and low birth weight (LBW)--the cohort that represents the highest proportion of illness and death among infants Despite these medical advances, recent longitudinal studies have provided clear evidence of physical health problems; cognitive and neuropsychological dysfunction; and other social, emotional, and behavioral problems among children born prematurely. A number of studies have indicated that premature and LBW infants are still at risk for psychosocial, physical, and mental problems despite the immediate contributions of post-natal interventions to their increased chance for survival The extant research has demonstrated that children born prematurely and LBW are at risk for problems in health, neuropsychological functioning, learning, academic achievement, behavior, and psychosocial adjustment. Research has further demonstrated that a variety of physical and psychological conditions are associated with poorer QOL among children. However, few studies have examined pediatric QOL among preterm school-aged children. Moreover, existing studies have not explored the relationship between cognitive, academic, and social/emotional functioning and QOL. The current study compared child and parent ratings of health-related quality of life among school-aged children born preterm (n = 26) and full-term (n = 28). Given the increased rates of physical, psychological, and cognitive problems among the preterm population, it was hypothesized that children born prematurely would have significantly poorer proxy-reported and self-reported QOL than children born preterm.

Prior studies have shown that the low-level microbiome in the placenta is most similar to the non-pregnant oral microbiome, suggesting a hematogenous route of bacterial transmission. Based on these studies, we theorized that a disruption of the normal balance of pathogenic and commensal microorganisms in the oral cavity will lead to conditions that favor colonization of the placenta and amniotic cavity, leading to inflammation and preterm birth. We hypothesized that an altered oral microbiome profile will promote preterm birth. Our study aimed to compare metagenomic profiles of saliva and tongue in women delivering preterm to those of women delivering at term. Unstimulated saliva and tongue brushings were collected according to an IRB-approved protocol from patients who delivered preterm, and from age and race-matched patients who delivered at term. Exclusion criteria included obvious risk factors for preterm birth or other major complications (multiple gestation; history of or current cervical cerclage; history of hypertension or diabetes; prior history of preterm birth or preeclampsia; age less than 16 or greater than 45) as well as immunologic problems (HIV, organ transplant, etc). Oral samples were collected within 24-48 hours after delivery. Samples were analyzed using 16S rDNA-based sequencing, where the DNA was extracted and then amplified by PCR using 16S rDNA primers. Data was processed using the UPARSE/SINTAX pipeline, and differentially abundant taxa were determined using the LEfSe method and MaAsLin2. The parent study enrolled 100 patients who delivered preterm and 205 patients who delivered at term. A subset of patients had oral samples collected, and 95 saliva and 70 tongue samples were analyzed using 16S rDNA-based sequencing. Communities from tongue and saliva were significantly different between women who delivered preterm and those who delivered at term, although not between those delivering low birthweight versus normal birthweight infants. When assessing beta diversity using the unweighted unifrac metric, patients who delivered very preterm (VPT, < 32 weeks) had a tongue microbiome that was consistently and statistically different from the tongue microbiome of patients who delivered both term (T, > 37 weeks) and late preterm (LPT, 32-<37). Differences remained significant after controlling for tobacco use. In a three-way comparison of saliva samples between the groups using MaAsLin2, the genus Lachnoanaerobaculum was significantly less abundant in the VPT group. Our studies suggest a tongue and salivary microbiome that differs between women delivering term and late preterm versus very preterm. Future studies are required to prospectively confirm differences and may yield data to design noninvasive tests to predict preterm birth risk. / 2021-06-12T00:00:00Z

BACKGROUND AND OBJECTIVE: It has been well established that children born preterm are at an increased risk of developing Autism Spectrum Disorder (ASD), and that risk increases as gestational age decreases. However, there is limited knowledge on how the ASD phenotype in preterm-born children compares to ASD presentation in children born at term. The objective of this study is to compare ASD core symptoms and characteristics commonly associated with ASD in children born extremely preterm (EP) and children born at term. METHODS: Extremely preterm (EP) participants (n=59) from the Extremely Low Gestational Age Newborn (ELGAN) Study who met diagnostic criteria for ASD at approximately 10 years of age were matched with term participants (n=59) from the Simons Simplex Collection (SSC) on age, sex, and nonverbal IQ. Differences in core ASD symptomatology were evaluated using the Autism Diagnostic Interview-Revised (ADI-R), an in-depth parent interview, and the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2), a semi-structured clinical observation assessment. Developmental milestones, anthropometrics, seizure disorder, and psychiatric symptoms were also investigated as associated characteristics of ASD. Analyses excluding multiplex EP individuals and their term matches, as well female-only analyses, were also conducted. RESULTS: On the ADI-R, the EP group had lower scores (decreased symptom severity) on verbal communication, specifically stereotypic language, and restricted and repetitive behaviors (RRBs). However, no between-group differences were observed with direct observation based on the ADOS-2 assessment. The EP group was more likely to have delayed speech milestones, lower height, weight, and head circumference, and lower rates of depression and anxiety symptoms. When 7 multiplex EP participants and their term control matches were eliminated from the sample, there were no differences from the primary analyses. Female-only analyses were similar to primary analyses on core ASD symptomatology findings. Regarding associated characteristics, females only differed on height, head circumference, and anxiety symptoms. CONCLUSIONS: Accounting for age, sex, nonverbal IQ, and prior ASD diagnosis status, EP children had less severe stereotypic language and RRB symptoms compared to term children based on ADI-R parent report, but exhibited no differences on parent-reported nonverbal communication or reciprocal social interaction symptoms, or with direct observation of social affective and repetitive and restricted ASD symptoms on the ADOS-2. EP children with ASD also showed decreased physical growth and delayed language relative to those born at term, possibly reflecting the developmental effects of being born EP. In sum, the ASD phenotype was generally similar between EP and term born children, with the exception of less severity of retrospectively parent-reported stereotypic behaviors, lower physical growth parameters, and increased delays in language milestones among EP born children with ASD.

No description available.

The purpose of this study was to examine the effects of multi-modal stimulation (differing amounts of light and vocal stimulation) on preterm infants' behavioral and state organization. Specifically, we looked at the effects that supplemental vocal stimulation (taped female voice) had when varied in amount of exposure (three times a day versus once a day) and when provided in different lighting conditions ("typical illumination" versus "decreased illumination"). Forty infants were placed in one of four groups: Standard Illumination/High Voice (SIHV), Standard Illumination /Low Voice (SILV), Decreased Illumination/High Voice (DIHV) and Decreased Illumination/Low Voice (DILV). Infants receiving standard illumination were exposed to the vocal stimulus in standard NICU lighting conditions (approximately 20 lux), whereas infants in the "low" lighting conditions were exposed to the stimulus in darkened conditions (approximately 3 lux). Infants receiving high vocal stimulation listened to a taped female voice three times a day, whereas infants receiving low vocal stimulation were exposed to the voice only once a day. Each infant received 10 minutes of exposure per session over five consecutive days. Infants were videotaped in their incubator for 10 minutes before, during, and after the stimulus exposure (total of 30 minutes) for each day. The videotapes were then scored on the infant's frequency of stress related behaviors and self-regulatory behaviors before, during, and after the stimulus for each day. Results indicated that both lighting levels and vocal stimulation altered preterm infants' stress and self-regulatory behaviors, and that these effects were dependent on both the day and the stimulus condition the infant was in. In addition, the vocal stimulation and lighting levels had an effect on the states that infants exhibited during and after the presentation of stimulation. These results suggest that the occurrence of different types and amounts of stimulation have an effect on behavioral organization of the preterm infant, and these effects are highly dependent on both history and context in which this stimulation is presented / Ph. D.

Synchronous interaction between adolescent mothers with preterm infants in the Neonatal Intensive Care Unit was examined in this study. Understanding the characteristics of synchrony in adolescent mother and premature infant interactions during this early period in the development of the relationship provides direction for the development of nursing strategies to foster synchronous interaction in the neonatal intensive care unit (NICU) setting and, subsequently, positive developmental outcomes for preterm infants. The research design was a one-group, pretest-posttest, exploratory intervention assessing synchronous interaction using the Nursing Child Assessment Feeding Scale (NCAFS) among 27 adolescent mothers and their premature infants in the NICU. The study examined the differences in adolescent mother-premature infant interaction in the NICU environment prior to an intervention and within 48 hours after receiving the Preterm Infant Cues Intervention (PICI). Additional variables including stress, social support, age of the adolescent mother and preterm infant, ethnicity, length of stay in the NICU, and preterm infant weight were considered. Results showed a statistically significant difference between Time 1 and Time 2 synchronous interaction measurements indicating that the PICI may have resulted in the adolescent mother better understanding the preterm infant’s behavior. The Caregiver Total Scale score (t = -3.93, p < .001) and the Total Scale score (t = -3.96, p < .001) were the two main scales that the PICI could have affected. There were no correlations among the other independent variables and the dependant variable. Future research should focus on a large scale longitudinal study to measure synchronous interaction over multiple time points beginning in the NICU carrying through the first year of child development. Adding a qualitative component to future studies would provide further insight into experience of adolescent mothers with preterm infants. / text

Definition of neurodevelopmental outcome from early brain imaging remains a priority for survivors of very preterm (VPT) birth given their persistently high rates of cognitive and motor difficulties. Volumes of the deep grey matter (DGM) structures were measured longitudinally using magnetic resonance imaging from 96 VPT infants studied within 2 weeks of birth and 70 at term-equivalent age. At 4 years of age, 36 children returned for neuropsychological assessments evaluating IQ, language function, and visual motor integration. Multiple hierarchical regressions examined associations of DGM growth with neuropsychological measures. Overall DGM growth, primarily attributed to the caudate and thalamus, predicted Full Scale IQ, core language and VMI scores after controlling for sex and total brain volume. Thalamic growth was additionally associated with measures of neonatal clinical severity, bronchopulmonary dysplasia, and white matter lesions. Longitudinal growth of the DGM, particularly the caudate and thalamus were established as early markers of long-term outcomes.