In all three phases, the majority of the secretory cell nuclei either had no evident nucleolus or exhibited nuclei with a single nucleolar corpuscle (Table 2). The young animals presented the largest percentages of nuclei, with two or multiple (more than two) nucleoli and consequently a larger mean number of nucleoli per nucleus in relation to the two other phases, indicating high proliferative ac- tivity. However, these parameters were not correlated proportionally by the area and perimeter nucleolar mea- surements (Table 1), and the total nucleolar area of the young group was smaller in relationship to that of the other two groups. The mean values of the perimeter and nucleolus/nucleus ratios for these parameters did not vary signiﬁcantly throughout postnataldevelopment, suggest- TABLE 1. Values of the morphometric-stereological data in the gerbil ventral prostate in three phases of
We previously reported that secreted phosphoprotein 1 (SPP1) mRNA is expressed in neurons whose axons form the corticospinal tract (CST) of the rhesus macaque, but not in the corresponding neurons of the marmoset and rat. This suggests that SPP1 expression is involved in the functional or structural specialization of highly developed corticospinal systems in certain primate species. To further examine this hypothesis, we evaluated the expression of SPP1 mRNA in the motor cortex from three viewpoints: species differences, postnataldevelopment, and functional/structural changes of the CST after a lesion of the lateral CST (l-CST) at the mid-cervical level. The density of SPP1-positive neurons in layer V of the primary motor cortex (M1) was much greater in species with highly developed corticospinal systems (i.e., rhesus macaque, capuchin monkey, and humans) than in those with less developed corticospinal systems (i.e., squirrel monkey, marmoset, and rat). SPP1-positive neurons in the macaque monkey M1 increased logarithmically in layer V during postnataldevelopment, following a time course consistent with the increase in conduction velocity of the CST. After an l-CST lesion, SPP1-positive neurons increased in layer V of the ventral premotor cortex, in which compensatory changes in CST function/ structure may occur, which positively correlated with the extent of finger dexterity recovery. These results further support the concept that the expression of SPP1 may reflect functional or structural specialization of highly developed corticospinal systems in certain primate species.
The study of the testicular parenchyma is a useful tool to evaluate the spermatogenic capacity in normal, pathologic and experimental conditions (Cardoso 2009). Several studies have quantified the testicular cells using different techniques, as proposed by Bellvé et al. (1977), but most of then use histomorphometry (Nunes et al. 2013, De Melo et al. 2013, Morais et al. 2014). Thus, this work aims to estimate the number of testicular cells in two Caviomorph rodents during the postnataldevelopment, applying design-based stereological techniques as an accurate tool.
Female Wistar rats from our breeding colony weighing approximately 200 g were mated overnight to males of the same stock, in a harem system. Vaginal smears were collected and the presence of sperm was used to determine gestational day 0. Ten to 12 pregnant dams per group were exposed to either 8 or 16 mg/kg of fluoxetine (F8 or F16) or 40 or 80 mg/kg of venlafaxine (V40 or V80) administered intragastrically by ga- vage from gestational day 15 to 20. A control group (C) was gavaged with the vehicle (wa- ter). Food and water consumption during treatment was recorded. Doses of fluoxetine were selected from a previous experimental study on the embryotoxicity of fluoxetine carried out on rats (14). In this study, the developmental no observed adverse effect level (NOAEL) was 12.5 mg/kg. We chose 8 and 16 mg/kg dose levels which were lower and slightly higher than the NOAEL for embryotoxicity in order to look for the po- tential functional toxicity of lower doses and in order to obtain information for the design of future studies on behavioral teratology. Functional and behavioral toxicity is assumed to occur at dose levels lower than those involved in embryotoxicity. Less informa- tion was available on the developmental ef- fects of venlafaxine. Therefore, we based our dose selection on the information from the manufacturer referring to experimental studies in which the only toxic effect re- ported was delayed rat development at the dose of 80 mg/kg. In our study we selected 40 and 80 mg/kg. Thus, we used a weight ratio of 5:1 for venlafaxine and fluoxetine in the present study. It should be pointed out that this same proportion of doses is reported in clinical practice (maximum dose levels of 80 mg/day and 275 mg/day for fluoxetine and venlafaxine, respectively).
Postnatal gelişme döneminde sıçan kaput epididi- misindeki AR dağılımını belirlemek için 21 ile 120 gün arasındaki değişik yaş gurubu sıçanlardan alı- nan doku kesitleri, immunohistokimyasal yöntemler kullanılarak incelendi. Tablo 1 de bu çalışmadan ve bu konuda yapılmış olan diğer çalışmalardan elde edilen sonuçlar karşılaştırmalı olarak gösterilmiştir.
Our results demonstrated that serum EPI levels of OAP rats were decreased in 2 weeks after birth. As the development of puberty, serum EPI increased gradually, and regained normal level. The expressions of PNMT protein in adrenal medulla showed the same tendency. However, ONP rats showed lower levels of serum EPI and the expressions of PNMT protein from birth to adulthood. The marker of AMCC is the synthesis and secretion of a large number of EPI, glucocorticoid induced expressions of synthetic enzyme PNMT that promoted the formation of EPI [26–28]. We presume that, although there existed impaired factors in asthma maternal uterus, adrenal medulla of offspring rats gradually were repaired during the development. We found that OVA-induced stress in asthma maternal rats during pregnancy enhanced significantly the serum levels of corticosterone in offspring rats from asthma and NGF maternal group from birth to adulthood. It is proved that the high glucocorticoids(GCs) concentrations in the adrenal medulla prevented the fiber outgrowth from medullary chromaffin cells in vivo  and contributed to the decrease of transformation adrenal cells into neurons [30,31]. GCs could promote the expression of PNMT in adrenal medulla that catalyzes the conversion of norepinephrine to epinephrine [32–34].Thus we inferred that high corticosterone level may lead to the recovery of EPI level in offspring. However the increase of corticosterone level could not completely antagonize the alteration of NGF on the adrenal medulla that promoted chromaffin cells to differentiate into sympathetic nerve cells from birth to puberty, and exogenous GCs supplement may be essential.
To date, very few studies on the roles of lncRNAs in mammalian testis development and spermatogenesis have been reported. Lee et al. identified a total of 50, 35 and 24 potential lncRNAs from type A spermatogonia, pachytene spermatocytes, and round spermatids, respectively, through searching SAGE data. Candidates were BLAST searched, mapped and RNA secondary structures were compared against various ncRNA databases. They found that levels of some lncRNAs decreased significantly following induction of differentiation by retinoic acid and the levels of several lncRNAs were decreased by more than a 1000-fold . A recent study revealed that an X-linked gene, Tsx, located within the X-inactivation center, is actually a new member of the lncRNA family and is abundantly expressed in meiotic germ cells. Tsx mutant male mice have smaller testes resulting from pachytene-specific apoptosis, indicating that Tsx performs general functions in male germ cell development . Another recent study found that a lncRNA, meiotic recombination hot spot locus (mrhl), negatively regulates Wnt signaling in mouse spermatogonial cells through its protein partner Ddx5/p68 .
We did find that postnatal mammary gland development is Akt1-dependent. Unlike embryonic growth, postnataldevelopment requires estrogen and progesterone, which are secreted by the ovaries at approximately three weeks of age in the mouse. Ductal outgrowth of inguinal mammary glands was significantly reduced in Akt1 2/2 glands during early and late pubertal time points. However, by adulthood these glands occupied the same amount of space in the fat pad as their wild-type counterparts. Our previous work indicated that Akt12/2 female mice had higher levels of estradiol and lower levels of progesterone than Akt1+/+ females during late puberty, but that these levels were similar in both genotypes by adulthood irrespective of Akt1 status . Consid- ering that postnatal ductal growth and alveolar expansion are dependent on estradiol and progesterone, the higher levels of progesterone most likely have a compensatory effect on ductal outgrowth, allowing for the Akt1 2/2 mammary glands to reach full size. Conversely, the levels of estradiol may be a contributing factor to the altered terminal end bud and alveolar expansion seen in the Akt12/2 glands. Mammary gland postnatal ductal development is driven by the rapid growth of the terminal end bud, a unique structure that contains dichotomously dividing stem cells during puberty. The terminal end bud contains a ‘tube within a tube’ structure, with an outer layer of undifferentiated cap cells and an inner layer of luminal epithelial cells. Both layers have high rates of mitosis, and normally have rates of forward growth through the fat pad of about 0.5 mm per day . Akt1 deficiency resulted in a significant decrease in the terminal end bud population during puberty, and a significant decrease in total alveolar buds and a strong trend for decreased alveolar bud size in adulthood. We also demonstrated that suppression of Akt1 in
The reduced ACE activity with enalapril treatment affects at least the function of two relevant physiological systems, RAS and kallikrein-kinin system. Classically, these systems have been linked to cardiovascular and inflammatory processes especially in adult phase. However, both systems also have pivotal roles during postnataldevelopment and their activation can change the maturation of the adipose tissue (Martins et al., 2008; Mori et al., 2008). Obesity resistance phenotype has been generated upon deletion of many receptors in these systems (Yvan-Charvet et al., 2005; Mori et al., 2008) as well as of the AngII precursor molecule angiotensinogen (Massiera et al., 2001), which corrob- orates the physiological relevance of these systems in the regula- tion of metabolic activity and body mass maintenance. Metabolic alterations were also obtained with the insertion of three copies of the ACE gene into the mouse genome, although divergent data have been observed. In this case the genetic augmenta- tion of ACE activity triggers a phenotype of decreased body fat and mass under hyperlipidic diet (Heimann et al., 2005), in opposition to other studies that point positive correlation between ACE activity and obesity (Davidson et al., 2011). These apparently contrasting findings could be due to other functions attributed to ACE not related to AngII production, like the sig- naling activity of the enzyme (Kohlstedt et al., 2005; Guimaraes et al., 2011).
this postnatal period may modulate the brain’s functional mat- uration and determine its lifelong integrity . Evidence from human studies has shown that some environmental stimuli such as physical activity habits in infancy and adolescence seem to have a favorable influence [3,11,22]. For instance, a positive cor- relation between physical activity and learning and intelligence scores has been observed in school-age children . In preado- lescent children, single or various exercise sessions may modify neuronal activity, improve the performance in attention tasks, and enhance reading comprehension and response accuracy in aca- demic achievement tests [3,11]. Data from animal studies have shown that exercise can modulate the functional maturation of the developing brain by means of neuroplastic processes [8,24]. In a study conducted by our group, we verified that an exercise program undertaken during adolescent period of rats was able to increase axonal density of granule cells of the dentate gyrus, to enhance hippocampal expression of neurotrophic factors, and to improve learning and memory . Together, these interesting data sug- gest that physical exercise during postnataldevelopment results in positive changes for the brain, particularly in the hippocampal formation – a highly plastic region of the brain linked to cognitive and emotional processes. However, it is important to point out that exercise-induced neuroplastic effects may vary according to animal age  and training intensity .
cleared in the heart. We have not yet elucidated the immune mechanisms responsible for viral clearance from the heart in our juvenile mouse model. However, the limited CD3 staining in the heart observed at 2 and 77 days is consistent with previous studies demonstrating a lack of functional antiviral T cells following CVB3 infection [40,41], and suggests that the type I interferon response may ultimately be responsible for controlling the viral infection . We observed that after CVB3 exposure in vivo, CPCs showed a strong tendency to differentiate into vascular cells. Additionally, CVB3 has been previously shown to upregulate autophagy, a cellular process which may be essential during cellular differentiation . Similar to DOX-induced senescence, CVB3-mediated premature differentiation reduced the number of CPCs available later in life. The role of CPCs in postnataldevelopment and physiologic remodeling is poorly understood, but observations drawn from the juvenile DOX model suggest that CPCs are important for vascular development in the growing heart as well as in response to physiologic hypertrophy during exercise and in postinfarction remodeling . The findings presented in this study support the hypothesis that a mild CVB3 infection early in development can impair the heart’s ability to undergo physiologic remodeling, leading to dilated cardiomyop- athy later in life.
The skewed XCI toward Cul4b null -bearing chromosome could be caused either by an initiation of XCI that favors the Cul4b null - bearing X or by a selection against Cul4b null -expressing cells during development. To distinguish between those two possibilities, we next examined the XCI pattern in younger Cul4b heterozygous females. As shown in Fig. 6B–C, the percentages of Cul4b- expressing cells in lung were not significantly different between Cul4b heterozygous and wild-type females even in the newborn. However, the percentages of Cul4b positive cells in kidney and liver were significantly lower in heterozygotes than in wild-type (Fig. 6B–C). These results suggest that the skewed XCI is caused by a gradual selection against the Cul4b negative cells and that different organs face differential selection pressure during prenatal and postnataldevelopment. While Cul4b null cells in lung were nearly all eliminated before birth, those cells remained in Figure 4. Growth retardation of Cul4b heterozygous mice during embryonic development. (A) Bodyweights of Cul4b heterozygous mice and littermate wild-type females after birth. Data were presented as mean6SD. N = 8, *: p,0.05; **: p,0.01; ***: p,0.001. (B–E) Representative photographs of Cul4b heterozygous embryos and littermate wild-type controls at 9.5 (B), 10.5 (C), 12.5 (D) and 14.5 (E) dpc. The bar represents 1 mm in (B–C) and 2 mm in (D) and (E), respectively.
nicotine-exposed offspring in this animal model would have altered beta cell function. As anticipated, developmental nicotine exposure resulted in altered insulin granule morphology and impaired GSIS compared to saline controls at 26 weeks of age. Electron microscopy (EM) analysis revealed a reduction in the total number of insulin granules within beta cells of nicotine- exposed offspring. Furthermore, there was a pronounced reduc- tion (18-fold) in the number of pale, immature secretory granules by 26 weeks, suggesting that proinsulin biosynthesis may be impaired in this animal model and thus contribute to the loss of beta cell function. Indeed, proinsulin gene transcription has been previously shown to be crucial for maintaining proinsulin biosynthesis, retaining islet insulin stores, and ultimately regulating glucose homeostasis . However, this finding of fewer immature insulin granules conflicts with EM studies in other animal models of dysglycemia, which have reported increased numbers of Figure 5. Insulin granule patterns during postnataldevelopment. The number per beta cell area of: A) total insulin granules (filled, immature and empty); B) immature insulin secretory granules (containing pale-staining proinsulin); and C) filled insulin granules (containing dense-core mature insulin). D) Representative electron microscopy photographs of saline and nicotine-exposed beta cells at 26 weeks of age illustrate both the typical insulin granule patterns (immature insulin granules are indicated by solid black arrows and mature insulin granules by striped arrows), and mitochondrial structures (indicated by white boxes); N = nucleus. All data are presented as mean6SEM. Values with an asterisk are significantly (p,0.05) different from saline controls.
Because the three mouse strains included in this study are known to exhibit differences in susceptibility to induced lung fibrosis (B6 > AJ > C3H) we investigated the strain-dependent expression levels of genes in the pro-fibrotic Wnt signaling pathway (Chilosi et al., 2003; Douglas et al., 2006; Konigshoff et al., 2008). A key regulator of epithelial-mesenchymal crosstalk (Wnt2b) exhibits increased expression in B6 mice relative to AJ or C3H throughout most of lung development. Further investigation of Wnt family genes identified increased postnatal expression of Wnt5a, Wnt10b, and Wnt11 in B6 mice relative to AJ/C3H as well as decreased expression of Wnt-inhibitory factor 1 (Wif1) in B6 compared to AJ/C3H (Fig. S10A ). Regression analysis confirmed significant strain-differences (P < .0001) in the expression of each of these Wnt-related genes as well frizzled receptors 3, 4, and 6 (Wnt2b, Wnt10b, Wnt11, Wif1, Fzd3, Fzd4, Fzd6 ). The expression profiles of 12 other genes associated with pulmonary fibrosis (MP:0006050) were not correlated between strains (Fig. S10B) as determined by regression analysis. Our analysis identified several additional genes with both strain-specific expression patterns and reported roles in pulmonary fibrosis or immune function, including Cysltr2 (B6 > AJ > C3H) (Beller et al., 2004), Asah1/Asah2 (B6 > AJ = C3H) (Dhami, He & Schuchman, 2010), Hck (B6 > C3H > AJ) (Ernst et al., 2002), Gas5 (B6 > AJ = C3H) (Song et al., 2014), and Cpa3 and Mcpt4 (C3H = AJ > B6) (Paun & Haston, 2012). These results suggest a potential role for Wnt signaling in the strain-dependent modulation of vascularization during alveolar development, as well as shed light on putative signaling pathways and immune modulators involved in conferring strain-dependent resistance susceptibility to pulmonary fibrosis.
O'Meara et al  have profiled the global gene expression patterns of mouse cardiomyo- cytes during differentiation. They examined the cardiomyocytes on postnatal day 0, 4, 7 and weeks 8–10 to identify genes and gene networks that change dynamically during the differenti- ation processes. They suggested that cardiac regeneration involves a transcriptional reversion of the cardiomyocyte differentiation process. Furthermore, Giudice et al. showed that extensive transcriptional changes and alternative splicing occurred in the heart between post- natal day 1 and 28. They demonstrated that alternative splicing played a role in vesicular traf- ficking and intracellular membrane organization. Their findings are consistent with our current data from the gene ontology enrichment analysis. Our reliance on a bioinformatics approach in the current study cannot directly verify the functional relevance of the key genes and regulators that we have identified. For functional follow-up study in the future, we will deliver and over-express adeno-associated virus carrying Gata4, Myh7, TNNI, Hand1, Hif3a and Cyclin A genes into cardiac fibroblasts that occupy the heart infract site. This could be combined with local administration of IGF1 and BMP10 to enhance cardiac regeneration, based on the findings from our results. Theoretically, over-expression of these factors might be able to promote the proliferation of adult cardiomyocytes and also directly reprogram cardiac fibroblasts into new cardiomyocytes.
In the current study, pockets of CD146+ cells accumulated in the neotendon only, and had a rounded morphology that was distinct from the appearance of fibroblasts. CD146 gene ex- pression was elevated at 3 days, and peaked at 7 days following overload. Scleraxis, which is a marker of the tendon fibroblast lineage , and MMP14, which is the membrane-tethered MMP chiefly responsible for fibroblast migration , displayed expression patterns similar to CD146. The transcription factors Egr1 and Egr2 play important roles in embryonic tendon de- velopment and in tendon regeneration following injury or in response to reloading after immo- bilization [26, 39–41]. In the current study, to our surprise, Egr1 expression was consistently lower in overloaded tendons than in non-overloaded tendons. This may be due to the acute and transient nature of Egr1 expression , and it is possible that changes in Egr1 expression occurred prior to the 3 day time point. Egr2 expression, however, was elevated over baseline at 3 days, and continued to increase until 7 days after overload, in a fashion similar to CD146 and scleraxis. Tenomodulin was downregulated at 3 days, and upregulated at 7 and 28 days, consis- tent with its described role as a marker of late tendon fibroblast differentiation . The pat- terns observed in CD146, scleraxis, Egr2 and tenomodulin expression, and the ability of pericytes to differentiate into fibroblasts in other tissues [36, 37], suggest a potential for peri- cytes to enter the tendon fibroblast lineage and contribute to postnatal tendon growth and ma- trix production. Another potential source of fibroblast progenitors are epithelial cells, through a process of epithelial-to-mesenchymal transition (EMT) . Tendons are surrounded by an epithelial layer of connective tissue , and the EMT-related genes Snail1, Slug, Twist1 and Gsc are coordinately expressed during the regeneration of injured tendons . In the current study, Snail1 expression is highly induced 3 days after overload and remains elevated through
METHODS: This is a prospective cohort study conducted with 1,121 pregnant aged 18 to 49 years, who attended the prenatal program devised by the Brazilian Family Health Strategy, Recife, PE, Northeastern Brazil, between July 2005 and December 2006. We interviewed 1,121 women during pregnancy and and 1,057 after childbirth. Unintended pregnancy was evaluated during the irst interview and postpartum depression symptoms were assessed using the Edinburgh Postnatal Depression Screening Scale. The crude and adjusted odds ratios for the studied association were estimated using logistic regression analysis. RESULTS: The frequency for unintended pregnancy was 60.2%; 25.9% presented postpartum depression symptoms. Those who had unintended pregnancies had a higher likelihood of presenting this symptoms, even after adjusting for confounding variables (OR = 1.48; 95%CI 1.09;2.01). When the Self Reporting Questionnaire (SRQ-20) variable was included, the association decreased, however, remained statistically signiicant (OR = 1.42; 95%CI 1.03;1.97). CONCLUSIONS: Unintended pregnancy showed association with subsequent postpartum depressive symptoms. This suggests that high values in Edinburgh Postnatal Depression Screening Scale may result from unintended pregnancy. DESCRIPTORS: Depression, Postpartum, epidemiology. Pregnancy, Unplanned. Pregnancy, Unwanted. Cohort Studies.
Thus far the use of electroporation in the brain has been largely limited to embryonic tissue. Injection of plasmids is typically performed in utero, where the delivery of the electrical pulse enables the constructs to enter cells . However, this is a surgical technique with significant risks of pup mortality . More recently, electroporation has been applied to the postnatal retina and cerebellum [4,7]. In our efforts to understand postnatal neurogenesis we developed a highly efficient and non-invasive procedure that utilizes electroporation for manipulating gene expression in the subventricular zone (SVZ). Here we introduce a method of electroporation in early postnatal animals that requires neither surgery nor stereotaxic apparatus, but which results in widespread expression of foreign genes in specific cell populations, with nearly 100% success rates. This methodology makes genetic manipulation in rodents a bench top procedure, bringing it within the technical and financial reach of most laboratories.
Figure 1. A flow chart summarizing the results of this and other studies investigating the postnatal periods of lowest and greatest larynx sensitivity to androgen exposure and the mechanism of vocal development in response to this exposure. Pink curves correspond to female F0 spectra and blue curves to male F0 spectra. (1) Normal development of F0 differentiation in males and females. Adrenarche and activation of the hypothalamus–pituitary–gonadal axis (gonadarche) are the main events leading to attainment of adult vocal patterns. At puberty, the larynx, vocal folds, and vocal tract (e.g., the resonance tube up to the oral cavity) acquire increased mass, leading to variable degrees of F0 reduction in men at adrenarche and gonadarche and to partial reduction in women at adrenarche. F0 decreases and then stabilizes between the ages of 14 and 18 years. Mean F0, which is shown for normal male and female Brazilian subjects , slightly decreases with age, as was shown in a study of normal Swedish women  and in other studies (Hollien and Shipp, 1972; Stoicheff, 1981; Hollien et al., 1994), due to steroids and other factors. (2) A hypothesis based on the study results postulating that androgen exposure during pre- and post-pubertal stages in CAH females causes fluctuations in androgen levels and permanent virilization of F0. (3) A good marker identified for the accumulated androgen effect (represented by Tanner stage) is shown for all ACT cases. Each full dot represents 4 months of androgen exposure. Androgen exposure during the pre-pubertal stage leading to decreased F0 was found in only 3 ACT cases (3/19; 15.7%), leading to development of the hypothesis that laryngeal tissue has a low level of sensitivity to androgen exposure during the first 5 postnatal years in females.