Spatial Transcriptomics of Aging Rat Ovaries Reveals Unexplored Cell Subpopulations with Reduced Antioxidative Defense.

INTRODUCTION: Ovarian aging is characterized by a gradual decline in quantity and quality of oocytes and lower chance of fertility. Better understanding the genetic modulation during ovarian aging can further address available treatment options for aging-related ovarian diseases and fertility preservation. METHODS: A novel technique spatial transcriptomics (ST) was used to investigate the spatial transcriptome features of rat ovaries. Transcriptomes from ST spots in the young and aged ovaries were clustered using differentially expressed genes. These data were analyzed to determine the spatial organization of age-induced heterogeneity and potential mechanisms underlying ovarian aging. RESULTS: In this study, ST technology was applied to profile the comprehensive spatial imaging in young and aged rat ovary. Fifteen ovarian cell clusters with distinct gene-expression signatures were identified. The gene expression dynamics of granulosa cell clusters revealed three sub-types with sequential developmental stages. Aged ovary showed a significant decrease in the number of granulosa cells from the antral follicle. Besides, a remarkable rearrangement of interstitial gland cells was detected in aging ovary. Further analysis of aging-associated transcriptional changes revealed that the disturbance of oxidative pathway was a crucial factor in ovarian aging. CONCLUSIONS: This study firstly described an aging-related spatial transcriptome changes in ovary and identified the potential targets for prevention of ovarian aging. These data may provide the basis for further investigations of the diagnosis and treatment of aging-related ovarian disorders.

A Potential Autophagy-Related-Gene Based Signature in Patients with Preeclampsia.

OBJECTIVE: Preeclampsia (PE) is a significant cause of maternal and offspring mortality and morbidity. The purpose of this study is to identify the potential diagnostic signatures of autophagy-related genes (ATGs) in pregnancies with preeclampsia. METHODS: The expression profile of mRNA was obtained from GSE75010 (placenta samples) and GSE48424 dataset (blood samples). The potential differentially expressed ATGs of PE were screened by R software. The gene-ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, correlation analysis, and protein-protein interactions (PPI) were applied for the differentially expressed ATGs. The diagnostic markers of PE were then screened based on least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine-recursive feature elimination (SVM-RFE). Receiver operating characteristic (ROC) analysis was used to investigate the predictive value of these diagnostic markers. Target miRNAs were predicted based on the miRDB, DIANA-micro T, Targetscan, and miRWalk databases, and were further validated in GSE84260. RESULTS: A total of 20 differentially expressed ATGs were identified between PE and healthy pregnancies. Functional analysis of differentially expressed ATGs indicated several enriched terms related to autophagy, apoptosis, angiogenesis, inflammation, immune response, hypoxia-inducible factor 1 (HIF-1), forkhead box O (FoxO) and AMP-activated protein kinase (AMPK) signaling pathway. A total of 12 ATGs were recognized based on LASSO and SVM-RFE, which made an excellent distinction in both the placenta tissues (area under the curve [AUC] = 0.903) and the blood samples (AUC = 0.972). Furthermore, four feature ATGs (leptin [LEP], ERO1-like [ERO1L], phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [PIK3CB], and mitogen-activated protein kinase 8 [MAPK8]) were screened and also shown an excellent diagnostic efficacy (AUC = 0.869 in placenta samples, and AUC = 0.914 in blood samples). Additionally, 81 target miRNAs were predicted according to the 4 feature ATGs. After evaluating the miRNA expression pattern of GSE84260, 11 miRNAs were selected. Finally, a miRNA-mRNA regulatory network was constructed, which may participate in the development of PE. CONCLUSIONS: We established an autophagy-related-gene based signature that may predict pregnancies with PE. And we also constructed a miRNA-mRNA regulatory network, which may deepen our understanding of the molecular mechanism underlying the development of PE.

Intestinal obstruction in pregnancy-a rare presentation of uterine perforation.

BACKGROUND: Intestinal obstruction is an uncommon non-obstetric condition during pregnancy which may cause maternal and fetal mortality. Clinicians are confronted with challenges in diagnosis and treatment of intestinal obstruction due to the overlapping symptoms, concerns over radiological evaluation, and surgical risks. CASE PRESENTATION: We reported a 39-year old, gravida 7, para 2, woman who suffered from acute intestinal obstruction at 34 weeks of gestation. Ultrasonography and abdominal computed tomography were applied for intestinal obstruction diagnose. Conservative treatment was initially attempted. But following ultrasound found the absence of fluid in the amniotic sac and the patient showed no improvement in clinical symptoms. An emergency caesarean section was then performed. Intra-operative assessment showed dense adhesion between the left wall of uterus and omentum, descending colon, and sigmoid colon. After adhesion dialysis, uterine rupture with complete opening of the uterine wall at the site of left uterine cornua was found without active bleeding. The uterine rupture was then repaired. CONCLUSIONS: Although uncommon during pregnancy, clinical suspicion of bowel obstruction is necessary especially in women with a history of abdominal surgery. Surgical intervention is indicated when conservative therapy fails and when there are signs of abnormal fetal conditions and worsened symptoms.

Association of surfactant protein D gene polymorphism with susceptibility to gestational diabetes mellitus: a case-control study.

BACKGROUND: Surfactant protein D (SP-D) is a critical component of the innate immune system intrinsically linked to energy metabolism. However, the relationship of SP-D gene polymorphisms and gestational diabetes mellitus (GDM) remains unclear. In this study, we analyzed SP-D gene polymorphisms in GDM patients and nondiabetic controls and then determined the association of SP-D gene polymorphisms with GDM. METHODS: We examined a common genetic polymorphism located in the SP-D coding region (rs721917, Met31Thr) in GDM patients (n = 147) and healthy pregnant controls (n = 97) by using a cleaved amplification polymorphism sequence-tagged sites (PCR-RFLP) technique. The level of SP-D protein in the serum of GDM patients and nondiabetic controls was determined by ELISA. The gene and allele frequencies of SP-D and their association with GDM as well as SP-D protein levels were analyzed and expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: We found that there was a significant association of the SP-D polymorphism (rs721917) with GDM. The SP-D (T/T) genotype was found in 11.6% and 21.6% of GDM patients and matched healthy controls, respectively (odds ratio, 0.473; 95% confidence interval, 0.235-0.952; P = 0.033), indicating that women with the (T/T) genotype had a lower prevalence of GDM (OR = 0.473). Women with the T/C genotype showed an increased risk of GDM (odds ratio, 2.440; 95% confidence interval, 1.162-5.123; P = 0.017). We did not observe corrections between glucose homeostasis markers and SP-D genotypes in women with GDM. Furthermore, serum SP-D levels were higher in GDM patients than in matched healthy controls. CONCLUSIONS: This study found the first evidence that an SP-D gene polymorphism (rs721917) was associated with GDM, which may provide the basis for further study on how SP-D plays a regulatory role in GDM.

Glycemic control and neonatal outcomes in women with gestational diabetes mellitus treated using glyburide, metformin, or insulin: a pairwise and network meta-analysis.

AIMS: We aimed to assess the comparative efficiency and safety of the use of glyburide, metformin, and insulin in gestational diabetes mellitus (GDM). METHODS: We searched for randomized controlled trials that compared glyburide, metformin, and insulin in GDM. Data regarding glycemic control and neonatal safety were collected and analyzed in pairwise and network meta-analyses. RESULTS: A total of 4533 individuals from 23 trials were included. Compared with glyburide, metformin reduced 2-h postprandial blood glucose (2HPG) to a greater extent (standard mean difference (SMD) 0.18; 95% credible interval (CI) 0.01, 0.34). There were significantly lower prevalence of neonatal hypoglycemia (risk difference (RD) - 0.07; 95%CI - 0.11, - 0.02) and preeclampsia (RD - 0.03; 95%CI - 0.06, 0) in the metformin group than in the insulin group. The metformin group had significantly lower birth weight (SMD - 0.17; 95%CI - 0.25, - 0.08) and maternal weight gain (SMD - 0.61; 95%CI - 0.86,- 0.35) compared with the insulin group. Network meta-analysis suggested that metformin had the highest probability of successfully controlling glycemia and preventing neonatal complications. CONCLUSIONS: The present meta-analysis suggests that metformin may be as effective as insulin for glycemic control and is the most promising drug for the prevention of neonatal and maternal complications.

Herniation of the amniotic sac through congenital uterine defect confirmed during operation: A case report.

Herniation of the amniotic sac into the peritoneal cavity or bladder is a rare but serious condition during pregnancy, which has not been reported in pored congenital uterine anomaly. Here, we report a rare case to draw obstetricians' attention to the atypical uterine rupture. A primigravida at 35 weeks of gestation was admitted for upper abdominal pain. A primary diagnosis of uterine rupture was made after finding the amniotic sac herniation through obstetric ultrasound. Exploration during emergent cesarean section revealed symmetrical pored defect on the uterine horn. The diagnosis of uterine anomaly was eventually made. The educational meaning of this rare case is that it is advisable to rule out uterine anomalies when signs of uterine rupture are suspected during pregnancy while contributory risk factors have not been identified. Besides, it is of vital importance to make a full assessment of both the mother and the fetus so to determine the appropriate time of termination.