Background: Intrauterine growth retardation (IUGR) is a common problem in human and other species and increases the risk of death of the fetus and newborn during the perinatal period. Objectives: This study was conducted to examine the influences of intrauterine growth retardation (IUGR) on development of the gastrointestinal tract in newborn pigs. Methods: Ten animals from five litters were divided into five piglets with IUGR and five with normal birth-weight (NW). The IUGR category comprised animals with a birth weight 2 SD below the mean birth weight of the total population, while the NW category included animals with a birth weight within one SD of the mean birth weight in the total population. Animals were anesthetized and sampled within 2–4 h after birth and without suckling. The morphological changes of intestine and stomach of IUGR piglets were compared with NW ones. The expressions of IGF-I and receptors for growth hormone and insulin in intestinal mucosa were semiquantified using reverse transcription PCR. Results: The results of our study indicated that the weights of the stomach, small intestine and small intestinal mucosa were significantly lower in IUGR compared with NW piglets (p < 0.01). In addition, the lengths of the small intestine and colon in IUGR pigs were also significantly less than those of NW (p < 0.05). Furthermore, insulin-like growth factor-I (IGF-I) mRNA level in intestinal mucosa of IUGR piglets was increased significantly (p < 0.05), and the expression mRNA levels of insulin receptor and growth hormone (GH) receptor in the mucosa in IUGR piglets showed a tendency to be lower (p = 0.17 and p = 0.11, respectively) than those of the NW animals. Conclusion: We conclude from the data that IUGR affects intestinal growth and morphology and is in associated with altered gene expression of growth-related proteins. We speculate that the morphological change and associated altered endocrine homeostasis contribute to lower growth rates of pigs affected by IUGR.

Saccharin sodium consumption is considered safe and beneficial, owing to its very intense sweetness without any associated calories, but supporting scientific data remain sparse and controversial. Herein, we demonstrate that dose-response relationships existed with regard to administration of saccharin or sucrose to mice for 35 days, and this association involved testis-expressed sweet-tasting molecules (taste receptor type 1 subunit 3 [T1R3]; G protein alpha-gustducin [Galpha]). Mouse body weights and testis weights in middle- and low-dose saccharin-treated groups were increased with up-expressions of molecules involved in testicular sweet taste and steroidogenic (middle saccharin: steroidogenic acute regulatory protein [StAR]; P450 cholesterol side-chain cleavage enzyme [CYP11A1]; 17-alpha-hydroxylase/C17,20-lyase [CYP17A1]; low saccharin: StAR). Moreover, a high-dose saccharin-related decline in reproductive hormone levels and injuries to testis and sperm were observed to be associated with suppression of testicular T1R3 and Galpha, as well as steroidogenic-related factors (StAR; 3-beta-hydroxysteroid dehydrogenase [3-beta-HSD]; CYP11A1; CYP17A1; 17-beta-hydroxysteroid dehydrogenase [17-beta-HSD]), and activation of cleaved caspase-3. However, abnormalities of the testis and sperm in high- and middle-dose sucrose-exposed mice were related to the increased-cleaved caspase-3, but independent of T1R3 and/or Galpha. Collectively, our results clearly suggest that saccharin-induced physiologic effects on testis are associated with testicular T1R3 and Galpha, which differed from sucrose. We hence call for a reassessment of the excessive use of sweeteners in daily life, especially artificial ones, considering their potential side effects.

To characterize inhibin secretion during the estrous cycle in guinea pigs, the concentrations of plasma inhibin, estradiol, progesterone, and FSH were determined. A significant positive correlation was observed between inhibin and estradiol throughout the estrous cycle. Plasma inhibin and estradiol started to increase a few days before ovulation (Day 0 = day of estimated ovulation), and decreased after ovulation. These two hormones remained low during the luteal phase. The immunoreactivity of inhibin alpha, betaA, and betaB subunits was colocalized in the granulosa cells of one or two healthy large follicles in the ovary before ovulation. There was no positive reaction of inhibin alpha and beta subunits in the corpora lutea or other follicles. Ovariectomy resulted in an abrupt decrease in plasma inhibin and a significant increase in plasma FSH. Injection of anti-inhibin serum into adult female guinea pigs induced an elevation in plasma FSH in a dose-dependent manner. This report presents the first description of sequential changes in plasma inhibin and estradiol during the estrous cycle of guinea pigs. Results suggest that inhibin is secreted mainly by granulosa cells of a few healthy large follicles in the ovary and that it plays an important role in the regulation of FSH secretion during the estrous cycle in guinea pigs.

-Young women with galactosemia experience ovarian failure at a very early age raising concern about the ovarian toxicity of galactose. While galactose may be present in the diet as a monosaccharide, it is predominantly derived from cleavage of the disaccharide lactose within the intestine. Our previous studies in animals have shown that high galactose diets inhibit ovarian follicular development and long-term exposure to high lactose diets retards growth of rats. The objective of the present study was to determine whether galactose exposure in the form of dietary lactose mimics the effects found previously with diets rich in galactose. Sixty female Long-Evans rats (25-day-old) were randomly assigned to two groups and fed a control diet (41.9% glucose in AIN93G [American Institute of Nutrition], CON) before lactose treatment. Unilateral ovariectomy (uOVX) was performed on half of the rats in each group to determine baseline ovarian follicle numbers. The study diet was a high lactose diet (HLD) containing 41.9% lactose in AIN93G. Study diet exposure started 1 month after uOVX (3 months old) and continued for 7 months in the treatment group. The control group remained on the 41.9% glucose diet throughout. Vaginal cytology, ovarian morphometric analyses, and serum concentrations of estradiol and progesterone were examined. Long-term exposure to the HLD decreased the body weights of animals and progesterone concentrations in the serum but produced no harmful effects on ovarian morphology or function. Beginning at 5 months of age (two months of lactose treatment) increasing numbers of females began to cycle irregularly but there was no difference between the glucose and lactose diet groups. These negative findings imply that administration of galactose in the form of lactose seems to be much less toxic than when galactose is fed to animals. From a human health perspective, these results are somewhat reassuring, since in general, women eat lactose-containing foods rather than foods that contain large amounts of free galactose.lactose / galactose / ovary / toxicology / rat

Preterm birth (PTB) is the leading cause of neonatal mortality and morbidity, with few prevention and treatment options. Uterine contraction is a central feature of PTB, so gaining new insights into the mechanisms of this contraction and consequently identifying novel targets for tocolytics are essential for more successful management of PTB. Here we report that myometrial cells from human and mouse express bitter taste receptors (TAS2Rs) and their canonical signaling components ( G-protein gustducin and phospholipase C β2). Bitter tastants can completely relax myometrium precontracted by different uterotonics. In isolated single mouse myometrial cells, a phenotypical bitter tastant (chloroquine, ChQ) reverses the rise in intracellular Ca concentration ([Ca]) and cell shortening induced by uterotonics, and this reversal effect is inhibited by pertussis toxin and by genetic deletion of α-gustducin. In human myometrial cells, knockdown of TAS2R14 but not TAS2R10 inhibits ChQ's reversal effect on an oxytocin-induced rise in [Ca] Finally, ChQ prevents mouse PTBs induced by bacterial endotoxin LPS or progesterone receptor antagonist mifepristone more often than current commonly used tocolytics, and this prevention is largely lost in α-gustducin-knockout mice. Collectively, our results reveal that activation of the canonical TAS2R signaling system in myometrial cells produces profound relaxation of myometrium precontracted by a broad spectrum of contractile agonists, and that targeting TAS2Rs is an attractive approach to developing effective tocolytics for PTB management.-Zheng, K., Lu, P., Delpapa, E., Bellve, K., Deng, R., Condon, J. C., Fogarty, K., Lifshitz, L. M., Simas, T. A. M., Shi, F., ZhuGe, R. Bitter taste receptors as targets for tocolytics in preterm labor therapy.

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MicroRNAs (miRNAs) are endogenous non-coding RNAs of ∼22 nucleotides in length that play important roles in multiple biological processes by degrading targeted mRNAs or repressing mRNA translation. To evaluate the roles of miRNA in porcine skeletal muscle, miRNA expression profiles were investigated using longissimus muscle tissue from pigs at embryonic day 90 (E90) and postpartum day 120 (PD120). First, we used previously known miRNA sequences from humans and mice to perform blast searches against the porcine expressed sequence tag (EST) database; 98 new miRNA candidates were identified according to a range of filtering criteria. These miRNA candidates and 73 known miRNAs (miRBase 13.0) from pigs were chosen for porcine miRNA microarray analysis. A total of 16 newly identified miRNAs and 31 previously known miRNAs were detected in porcine skeletal muscle tissues. During later foetal development at E90, miR-1826, miR-26a, miR-199b and let-7 were highly expressed, whilst miR-1a, miR-133a, miR-26a and miR-1826 showed highest abundance during the fast growing stage at PD120. Using the 47 miRNAs detected by the microarray assay, we performed further investigations using the publicly available porcine mRNA database from NCBI and computed potential target hits using the software rnahybrid. This study identified 16 new miRNA candidates, computed potential target hits for 18 miRNA families and determined the miRNA expression profiles in porcine skeletal muscle tissues at different developmental stages. These results provide a valuable resource for investigators interested in post-transcriptional gene regulation in pigs and related animals.

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