ABSTRACT
The potential risk of yellow fever (YF) infection in unvaccinated pregnant women has aroused serious concerns. In this study, we evaluated the effect of the YF vaccine during gestation using a mouse model, analyzing placental structure, immunolocalization of the virus antigen, and viral activity at the maternal-fetal barrier and in the maternal liver and fetus. The YF vaccine (17DD) was administered subcutaneously at a dose of 2.0 log10 PFU to CD-1 mice on gestational days (gd) 0.5, 5.5, and 11.5 (n = 5-10/group). The control group received sterile saline (n = 5-10/group). Maternal liver, implantation sites with fetus, and placentas were collected on gd18.5. The numbers of implantation sites, reabsorbed embryos, and stillborn fetuses were counted, and placentas and live fetuses were weighed. Tissues (placenta, fetuses, and liver) of vaccinated pregnant mice on gd5.5 (n = 15) were paraffin-embedded in 10% buffered-formalin and collected in TRIzol for immunolocalization of YF vaccine virus and PCR, respectively. PCR products were also subjected to automated sequence analysis. Fetal growth restriction (p < 0.0001) and a significant decrease in fetal viability (p < 0.0001) occurred only when the vaccine was administered on gd5.5. In stillbirths, the viral antigen was consistently immunolocalized at the maternal-fetal barrier and in fetal organs, suggesting a transplacental transfer. In stillbirths, RNA of the vaccine virus was also detected by reverse transcriptase-PCR indicating viral activity in the maternal liver and fetal tissues. In conclusion, the findings of this study in the mouse suggest that vaccination did not cause adverse outcomes with respect to fetal development except when administered during the early gestational stage, indicating the implantation period as a susceptible period in which the YF vaccine virus might interfere with pregnancy.
ABSTRACT
Serum levels of estrogen decrease at climacterium and directly interfere with the urogenital tract. Urinary bladder (UB) is responsive to hormonal changes, especially estrogen. Resistance exercise elicits benefits on severe chronic diseases. Nevertheless, it is still unclear whether the resistance exercise directly affects the UB in ovariectomized (OVx) rats. This study focused on investigating the effects of resistance exercise on UB function and morphology in OVx and control rats. Adult female Wistar rats (â¼250-300 g, 14-16 weeks old) [control (n = 20) and OVx (n = 20)] were divided in the following groups: sedentary (SED), and trained over 1 week (acute), 3 weeks (intermediate), and 10 weeks (chronic). Training was carried out in a ladder, with six bouts in alternate days with 75% of body weight load attached to the tail of the animal. Afterward, the animals were isoflurane anesthetized for evaluation of intravesical pressure (IP) changes upon topical administration of acetylcholine (Ach) and noradrenaline (NE) on the UB. At the end of the experiment, the UB was harvested for histological analysis and stained with hematoxylin-eosin and picrosirius red. Ach increased the IP in both OVx and control rats, whereas NE decreased the IP. However, the acute and intermediate groups showed attenuated responses to Ach and NE, while the chronic groups recovered the responses to Ach and NE close to those observed in SED groups. Acute and intermediate groups also showed decreased thickness of the muscular layer, with a reversal of the process with chronic training. In the OVx groups, the acute training reduced the thickness of the smooth muscle and mucosal layers, whereas chronic training increased it. Urothelium thickness decreased in the OVx SED and acute groups. Collagen type I fibers (CI-F) reduced in OVx SED acute and intermediate groups, while collagen type III fibers (CIII-F) increased in the OVx acute group. In the mucosal layer, the volume density of CFs reduced in OVx rats compared to control groups and chronic training resulted in their recovery. Our data suggest that chronic resistance exercise for 10 weeks reversed the functional and morphological changes caused by hypoestrogenism.
