There is still controversy over whether structural and morphological changes can be observed in tissues depending on the carbon dioxide (CO2) nature or the applied intra-abdominal pressures (IAP). This study aimed to investigate the effects of different pressure or CO2 nature used for pneumoperitoneum in gynecological laparoscopic surgery on inflammation, DNA damage, oxidative stress, and histopathological changes in ovarian and peritoneal tissue. For this purpose, forty female rats were randomly divided into 6 groups and different pneumoperitoneum models were created in these groups. Rats in group other than control and sham groups received standard (CD) or heated-humidified CO2 (HH) insufflations at low (4mmHg) or high pressure (8mmHg). The ovary and peritoneum sections were evaluated microscopically for apoptotic index (API) and API scoring was calculated. Tissue and plasma interleukin-6 (IL-6), tumor necrotizing factor-alpha (TNF-α), anti-Mullerian hormone (AMH) and 8-hydroxydeoxyguanosine (8-OHdG) levels were analyzed with enzyme-linked immunosorbent assay (ELISA). The most severe changes occurred in the 8CD group microscopically, while the least severe changes occurred in the 4HH group. All histopathological parameters except for ovarian apoptotic index and peritoneal PCNA at low pressure were higher in the CD group. TNF-α and 8-OHdG levels were higher in the CD group at both low and high pressures. Standard CO2 caused more prominent histopathological changes at high pressures and systemic inflammation in both pressure groups. The least change between the experimental study groups in terms of histopathological and biochemical was observed in the low-pressure heated-humidified group.

The developmental competence of oocytes is acquired gradually during follicular development, mainly through oocyte accumulation of RNA molecules and proteins that will be used during fertilization and early embryonic development. Several attempts to develop in vitro culture systems to support preantral follicle development up to maturation are reported in the literature, but oocyte competence has not yet been achieved in human and domestic animals. The difficulties to have fertilizable oocytes are related to thousands of mRNAs and proteins that need to be synthesized, long-term duration of follicular development, size of preovulatory follicles, composition of in vitro culture medium, and the need of multi-step culture systems. The development of a culture system that maintains bidirectional communication between the oocyte and granulosa cells and that meets the metabolic demands of each stage of follicle growth is the key to sustain an extended culture period. This review discusses the physiological and molecular mechanisms that determine acquisition of oocyte competence in vitro, like oocyte transcriptional activity, follicle and oocyte sizes, and length and regulation of follicular development in murine, human, and domestic animal species. The state of art of in vitro follicular development and the challenges to have complete follicular development in vitro are also highlighted.

We downloaded gene expression data, clinical data, and somatic mutation data of cervical squamous cell carcinoma (CSCC) patients from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Predictive lncRNAs were screened using univariate analysis and least absolute shrinkage and selection operator (LASSO) regression, and risk scores were calculated for each patient according to the expression levels of lncRNAs and regression coefficients to establish a risk model that could be a novel signature. We assessed the correlation between immune infiltration status, chemotherapeutics sensitivity, immune checkpoint proteins (ICP), and the signature. Therefore, we selected 11 immune-related lncRNAs (WWC2,AS2, STXBP5.AS1, ERICH6.AS1, USP30.AS1, LINC02073, RBAKDN, IL21R.AS1, LINC02078, DLEU1, LINC00426, BOLA3.AS1) to construct the risk model. Patients who were in the high-risk group had a shorter survival time than those in the low-risk group (p < 0.001). Risk scores in the signature were negatively correlated with macrophage M1, macrophage M2, and T cell CD8 + ; what's more, T cell CD8 + was higher in the low-risk group. The expression levels of ICP such as PD-L1, PD-1, CTLA-4, TIGIT, LAG-3, and TIM-3 were substantially higher in the low-risk group. For chemotherapeutic agents, high-risk scores were associated with higher half-inhibitory concentrations (IC50) of cisplatin. These findings suggested that the risk model can be a novel signature for predicting CSCC patients' prognosis, and it also can be used to formulate clinical treatment plans for CSCC patients.

The objective of this study was to identify predictable maternal serum signatures of cortisol metabolism during the first trimester of women who are expected to deliver small-for-gestational-age (SGA) neonates. This prospective cohort study included 112 pregnant women (with and without SGA, n = 56 each). Maternal serum samples were collected at 10-14 gestational weeks to quantify the levels of cortisol and its precursors and metabolites by liquid chromatography-mass spectrometry. Increased maternal serum levels of tetrahydrocortisol (11.82 ± 8.16ng/mL vs. 7.51 ± 2.90ng/mL, P < 0.005) and decreased 21-deoxycortisol (2.98 ± 1.36ng/mL vs. 4.33 ± 2.06ng/mL, P < 0.0001) were observed in pregnant women carrying SGA fetus. In conjunction with individual steroid levels, metabolic ratios corresponding to the activity of related enzymes were calculated. In addition to increased tetrahydrocortisol/cortisol ratio (P < 0.006), the SGA group showed a significant increase in the two metabolic ratios including cortisol/11-deoxycortisol (P < 0.03) and cortisol/21-deoxycortisol (P < 0.0003). The receiver operating characteristic (ROC) curve generated in combination with three variables of 21-deoxycortisol concentration and two metabolic ratios of cortisol/21-deoxycortisol and tetrahydrocortisol/cortisol resulted in an area under the ROC curve = 0.824 (95% confidence interval, 0.713-0.918). A significant decrease in maternal serum levels of 21-deoxycortisol and an increase in two metabolic ratios of cortisol/21-deoxycortisol and tetrahydrocortisol/cortisol, indicating cortisol biosynthetic rate, represent potential biomarkers for the prediction of SGA in the first trimester.

Meckel-Gruber syndrome (MKS) is a rare lethal autosomal recessive inherited disorder. Missed diagnosis might happen in clinical works due to an unclear genotype–phenotype correlation. We analyzed two families visiting our center; the parents are normal; each of the family aborted a fetus at 12WG. Following ultrasonography and pathological examination, both were diagnosed as MKS. Whole exome sequencing identified a compound heterozygous of two novel variants of CEP290 and a heterozygous of a novel variant of CC2D2A. Frameshift mutations in ZNF77 were also detected. Western blot analyzing whole-brain tissue showed that the expression of ZNF77, CC2D2A, and CEP290 was enhanced. HEK293T transfected with over-expression wildtype/mutated ZNF77 plasmid showed that SHH was increased in wildtype ZNF77 cells, while SHH and CC2D2A were increased in mutated ZNF77 cells. Our research provided two novel pathogenic variants of CEP290 and CC2D2A and suggested that ZNF77 might promote the expression of CC2D2A and regulate the amount of SHH.

Macrophages are known to be pivotal for ensuring the establishment of the immune tolerance microenvironment at the maternal–fetal interface. In particular, trophoblasts stay in close contact with decidual macrophages (DMs), which have been reported to play an active role in the modulation of the polarization of DMs. Thus, any dysfunction of trophoblasts might be associated with certain pregnancy‐related complications, such as recurrent spontaneous abortion (RSA). Enhancer of zeste homolog 2 (EZH2) is an important epigenetic regulatory gene that has been previously shown to be related to immune regulation. The present study assessed the expression of EZH2 in villi tissue obtained from healthy controls and RSA patients. Trophoblasts conditioned medium was collected to incubate macrophages differentiated from the THP‐1 cell line. The expression and function of EZH2 in trophoblasts were knocked down either by the use of siRNA or GSK126 as an inhibitor. Our results show a significant decrease in the expression of EZH2 in villi tissue from RSA patients as compared to healthy controls. Further, the inhibition of expression or function of EZH2 in trophoblasts promoted M1 macrophage polarization, which might be involved in the pathogenesis of RSA. Moreover, the suppression of EZH2 was found to affect the secretion of immune and inflammatory cytokines in trophoblasts. Altogether, these results indicated the importance of EZH2 in the regulation of immune functions of trophoblasts and thus highlighted its potential to be explored as a therapeutic target to prevent and treat pregnancy loss.

Rec ent studies have suggested a closer association between angiotensin-converting enzyme (ACE) gene polymorphisms and polycystic ovary syndrome (PCOS) risk, but the results were inconsistent. We conducted this meta-analysis to explore the precise associations between ACE gene I/D polymorphism and PCOS risk. Online electronic databases (PubMed, Embase, SCI index, CNKI, and Wanfang) were searched. Odds ratios (ORs) with 95% confidence interval (CIs) were calculated to assess the association between ACE gene I/D polymorphism and PCOS risk. In addition, heterogeneity, accumulative/sensitivity analysis, and publication bias were conducted to check the statistical power. Overall, 12 published case-control studies with 2248 patients and 1759 controls were included according to the criteria. Significant increased risk was found for PCOS susceptibility with I/D mutation (D vs. I: OR = 1.62, 95%CI = 1.24-2.11, P < 0.01, I2 = 86.1%; DD vs. II: OR = 2.10, 95%CI = 1.35-3.27, P < 0.01, I2 = 79.8%; ID + DD vs. II: OR = 1.57, 95%CI = 1.06-2.32, P = 0.02, I2 = 79.3%; DD vs. II + ID: OR = 1.91, 95%CI = 1.39-2.65, P < 0.01, I2 = 79.1%). Furthermore, some similar associations were also observed in subgroups. In summary, the current evidences indicated that ACE gene I/D polymorphism plays an important role in PCOS development, both in Asian and Caucasian descendants.

In placenta percreta cases, large vessels are present on the precrete surface area. As these vessels are not found in normal placentation, we examined their histological structure for features that might explain the pathogenesis of neoangiogenesis induced by placenta accreta spectrum disorders (PAS). In two patients with placenta percreta (FIGO grade 3a) of the anterior uterine wall, one strikingly large vessel of 2 cm length was excised. The samples were formalin fixed and paraffin-embedded. Gomori trichrome staining was used to evaluate the muscular layers and Weigert-Van Gieson staining for elastic fibers. Immunohistochemical staining of the vessel endothelium was performed for Von Willebrand factor (VWF), platelet endothelial cell adhesion molecule (CD31), Ephrin B2, and EPH receptor B4. The structure of the vessel walls appeared artery-like. The vessel of patient one further exhibited an unorderly muscular layer and a lack of elastic laminae, whereas these features appeared normal in the vessel of the other patient. The endothelium of both vessels stained VWF-negative and CD31-positive. In conclusion, this study showed VWF-negative vessel endothelia of epiplacental arteries in placenta accreta spectrum. VWF is known to regulate artery formation, as the absence of VWF has been shown to cause enhanced vascularization. Therefore, we suppose that PAS provokes increased vascularization through suppression of VWF. This process might be associated with the immature vessel architecture as found in one of the vessels and Ephrin B2 and EPH receptor B4 negativity of both artery-like vessels. The underlying pathomechanism needs to be evaluated in a greater set of patients.

Uterine leiomyomas are benign, estrogen-sensitive, fibrotic smooth muscle cell tumors occurring in the uterine myometrium. Leiomyomas are a considerable health burden, with a lifetime prevalence of 80% and limited treatment options. Estrogen and progesterone have positive effects on leiomyoma growth, but little is known about the roles of other hormones. One hormone of interest is prolactin, as it has been described to be present and functional in leiomyomas. The current study investigates prolactin production within leiomyomas and its effects on myometrial cells. RNA isolation and quantitative-PCR of human leiomyoma samples relative to matched adjacent myometrium confirms significant expression of prolactin and dopamine receptor D2, a known regulator of prolactin production and release in the pituitary, with no difference in prolactin receptor expression. Immunohistochemistry confirms increased prolactin in leiomyomas compared to adjacent myometrium and uteri from women without leiomyomas. These results suggest that leiomyomas contain cells that produce prolactin, which may then promote signaling in leiomyoma cells to regulate leiomyoma development/growth. Accordingly, we find that prolactin robustly activates STAT5 and MAPK signaling in rat and human myometrial cell lines. Furthermore, prolactin stimulates expression of myofibroblast markers in rat myometrial cells. Our findings suggest that local prolactin production in leiomyomas may stimulate trans-differentiation of myometrial cells to myofibroblasts, which in turn contributes to the fibrotic nature of leiomyomas.

We examined the influence of confined placental mosaicism (CPM) as a cause of fetal growth restriction (FGR), and whether CPM can be screened using cell-free DNA (cfDNA) analysis of the maternal plasma. We analyzed cfDNA in the maternal plasma of 40 FGR cases with an estimated fetal weight of less than - 2.0 SD using massively parallel sequencing to detect chromosomal aberrations. Fetal and placental genotyping was performed to confirm CPM cases. cfDNA analyses of maternal plasma detected suspected CPM cases with chromosomal aneuploidy or copy number variations in 5 of 40 cases (12.5%). For 4 cases in which the entire placenta consisted of cells with chromosomal abnormalities, fetal growth was severely restricted. CPM can be screened by cfDNA analysis in maternal plasma, accounting for approximately 10% of the causes of moderate or severe FGR, and the higher the proportion of abnormal karyotype cells in the placenta, the more severe the placental dysfunction and FGR.