LncRNA MEG3 alleviates PFOS induced placental cell growth inhibition through its derived miR-770 targeting PTX3.

Perfluorooctane sulfonic acid (PFOS) is a persistent environmental pollutant. Exposure to PFOS has been associated with abnormal fetal development. The long non-coding RNA (lncRNA) has been showed to play a role in fetal growth restriction (FGR), preeclampsia (PE) and other pregnancy complications. Whether the lncRNA contributes to PFOS-induced toxicity in the placenta remains unknown. In this study, we investigated the function of lncRNA MEG3 and its derived miR-770 in PFOS-induced placental toxicity. Pregnant mice received gavage administration of different concentrations of PFOS (0.5, 2.5, and 12.5 mg/kg/day) from GD0 to GD17, and HTR-8/SVneo cells were treated with PFOS in the concentrations of 0, 10-1, 1, 10 µM. We found that expression levels of miR-770 and its host gene MEG3 were reduced in mice placentas and HTR-8/SVneo cells with exposure of PFOS. A significant hypermethylation was observed at MEG3 promoter in placentas of mice gestational-treated with PFOS. We also confirmed that MEG3 and miR-770 overexpression alleviated the cell growth inhibition induced by PFOS. Furthermore, PTX3 (Pentraxin 3) was identified as the direct target of miR-770 and it was enhanced after PFOS exposure. In summary, our results suggested that MEG3 alleviate PFOS-induced placental cell inhibition through MEG3/miR-770/PTX3 axis.

PFOS Inhibited Normal Functional Development of Placenta Cells via PPARγ Signaling.

Perfluorooctane sulfonic acid (PFOS), a persistent environmental pollutant, has adverse effects on gestation pregnancy. Peroxisome proliferator-activated receptor γ (PPARγ) is involved in angiogenesis, metabolic processes, anti-inflammatory, and reproductive development. However, the function of PPARγ in PFOS evoked disadvantageous effects on the placenta remain uncertain. Here, we explored the role of PPARγ in PFOS-induced placental toxicity. Cell viability, cell migration, angiogenesis, and mRNA expression were monitored by CCK-8 assay, wound healing assay, tube formation assay, and real-time PCR, respectively. Activation and overexpression of PPARγ were conducted by rosiglitazone or pcDNA-PPARγ, and inhibition and knockdown of PPARγ were performed by GW9662 or si-PPARγ. Results revealed that PFOS decreased cell growth, migration, angiogenesis, and increased inflammation in human HTR-8/SVneo and JEG-3 cells. Placenta diameter and fetal weight decreased in mice treated with PFOS (12.5 mg/kg). In addition, rosiglitazone or pcDNA-PPARγ rescued cell proliferation, migration, angiogenesis, and decreased inflammation induced by PFOS in HTR8/SVneo and JEG-3 cells. Furthermore, GW9662 or si-PPARγ exacerbated the inhibition of cell viability, migration, angiogenesis, and aggravated inflammation induced by PFOS in HTR-8/SVneo and JEG-3 cells. Meanwhile, the results of mRNA expression level were consistent with the cell representation. In conclusion, our findings revealed that PFOS induced placenta cell toxicity and functional damage through PPARγ pathway.

Analysis of pelvic floor electrical physiological parameters in nulliparous women with stress urinary incontinence.

BACKGROUND: To investigate the changes in pelvic floor electrical physiological parameters in nulliparous women with stress urinary incontinence (SUI). METHODS: A retrospective survey was conducted on 922 women aged 20-40 years who received health examinations at the First Affiliated Hospital of Nanjing Medical University between July 2017 and December 2019. The women were split into two groups: those who had SUI (n=87) and those that did not (n=835). Questionnaires and pelvic floor electrical physiological indexes were collected. RESULTS: The mean age of the group of women with SUI was 29.77 years, while the mean age of the group of women with no SUI was 24.49 years. The body mass indexes (BMI) of the women with SUI were significantly higher than those of the women with no SUI. Importantly, the normal rates of type I and II fibers in the women with SUI were obviously lower than those in the women with no SUI. Moreover, the vaginal dynamic pressure in the women with SUI was significantly lower than in the women with no SUI. The study also found that the incidence of SUI in nulliparous women was higher in those aged 30-40 and that both low-weight and obese women had an increased risk of SUI. Type I and type II muscle fibers were more abnormal in the women with SUI than in those with no SUI. In multivariate logistic regression, the ages, BMIs, and type I fiber indexes of nulliparous women were related to SUI. CONCLUSIONS: Nulliparous women have a higher rate of SUI. Compared to women with no SUI, the possible potential risk factors are age (>30 years), higher BMI, and abnormal type I muscle fiber of the pelvic floor.

PPARγ Regulates Triclosan Induced Placental Dysfunction.

Exposure to the antibacterial agent triclosan (TCS) is associated with abnormal placenta growth and fetal development during pregnancy. Peroxisome proliferator-activated receptor γ (PPARγ) is crucial in placenta development. However, the mechanism of PPARγ in placenta injury induced by TCS remains unknown. Herein, we demonstrated that PPARγ worked as a protector against TCS-induced toxicity. TCS inhibited cell viability, migration, and angiogenesis dose-dependently in HTR-8/SVneo and JEG-3 cells. Furthermore, TCS downregulated expression of PPARγ and its downstream viability, migration, angiogenesis-related genes HMOX1, ANGPTL4, VEGFA, MMP-2, MMP-9, and upregulated inflammatory genes p65, IL-6, IL-1ß, and TNF-α in vitro and in vivo. Further investigation showed that overexpression or activation (rosiglitazone) alleviated cell viability, migration, angiogenesis inhibition, and inflammatory response caused by TCS, while knockdown or inhibition (GW9662) of PPARγ had the opposite effect. Moreover, TCS caused placenta dysfunction characterized by the significant decrease in weight and size of the placenta and fetus, while PPARγ agonist rosiglitazone alleviated this damage in mice. Taken together, our results illustrated that TCS-induced placenta dysfunction, which was mediated by the PPARγ pathway. Our findings reveal that activation of PPARγ might be a promising strategy against the adverse effects of TCS exposure on the placenta and fetus.

PFOS-induced placental cell growth inhibition is partially mediated by lncRNA H19 through interacting with miR-19a and miR-19b.

Perfluorooctane sulfonic acid (PFOS), a persistent environmental pollutant, has been associated with decreased birth weight. The dysregulation of long non-coding RNA (lncRNA) H19 has been implicated in pregnancy complications such as intra-uterine growth retardation (IUGR), preeclampsia (PE), however, the expression and function of H19 in PFOS-exerted detrimental effects in the placenta remains to be unveiled. Here, we explored the role of H19 in PFOS-induced placental toxicity. Results showed that PFOS caused decreased cell growth in human HTR-8/SVneo cells. Expression of H19 was increased, while miR-19a and miR-19b expression were decreased in mice placenta tissues and in HTR-8/SVneo cells exposed to PFOS. A significant hypomethylation was observed at the H19 promoter in the placentas of mice that were gestational exposed to high dose of PFOS. H19 was confirmed to bind with miR-19a and miR-19b, targeting SMAD4. Furthermore, H19 appeared to partially improve the cell growth of HTR-8/SVneo cells exposed to PFOS via upregulation of miR-19a and miR-19b. In summary, our findings revealed that H19/miR-19a and miR-19b/SMAD4 axis exerted important functions in PFOS-induced placenta cell toxicity.

[Lacrimal intubation with the Ritleng system in congenital nasolacrimal duct obstruction in children].

OBJECTIVE: To evaluate the efficacy and complication of the Ritleng lacrimal intubation system in the treatment of congenital nasolacrimal duct obstruction. METHODS: In this retrospective cases series, 148 patients (187 eyes) with congenital nasolacrimal duct obstruction between 2006 and 2007 from Beijing Children's Hospital, whose age ranged from 5 to 40 months (average 13 months), underwent silicone intubation with the Ritleng lacrimal intubation system, who received unsuccessful probing procedure previously. The therapeutic effect including dacryorrhea disappearance and lacrimal passages excretory function regaining was observed and the complications such as epistaxis, lacrimal duct edema or silicone tube prolapse were recorded. The follow-up period was from 4 to 17 months (average 11 months). RESULTS: Dacryorrhea disappeared in 157 eyes (84.0%) within 1 - 3 days after the surgery. The tubes were left in the place for 3 or 6 months. All the 187 eyes were successfully taken out of tubes. As follow-up, the overall successful rate was 95.2% (178/187). Seven eyes (3.7%) relief from symptoms and two eyes (1.1%) were ineffective. 46 cases (52 eyes), whose ages were about 5 months, regained normal lacrimal passages excretory function within 1 month after surgery. Complication included epistaxis (9 eyes) and lacrimal duct edema (9 eyes). The silicone tube prolapsed in eight eyes (4.3%). CONCLUSIONS: The Ritleng lacrimal intubation system is an easy, effective and nontraumatizing procedure for the treatment of congenital nasolacrimal duct obstruction. The lacrimal intubation procedure offers an early and active treatment for congenital nasolacrimal duct obstruct patients.