Fertility loss: negative effects of environmental toxicants on oogenesis

There has been a global decline in fertility rates, with ovulatory disorders emerging as the leading cause, contributing to a global lifetime infertility prevalence of 17.5%. Formation of the primordial follicle pool during early and further development of oocytes after puberty is crucial in determining female fertility and reproductive quality. However, the increasing exposure to environmental toxins (through occupational exposure and ubiquitous chemicals) in daily life is a growing concern; these toxins have been identified as significant risk factors for oogenesis in women. In light of this concern, this review aims to enhance our understanding of female reproductive system diseases and their implications. Specifically, we summarized and categorized the environmental toxins that can affect oogenesis. Here, we provide an overview of oogenesis, highlighting specific stages that may be susceptible to the influence of environmental toxins. Furthermore, we discuss the genetic and molecular mechanisms by which various environmental toxins, including metals, cigarette smoke, and agricultural and industrial toxins, affect female oogenesis. Raising awareness about the potential risks associated with toxin exposure is crucial. However, further research is needed to fully comprehend the mechanisms underlying these effects, including the identification of biomarkers to assess exposure levels and predict reproductive outcomes. By providing a comprehensive overview, this review aims to contribute to a better understanding of the impact of environmental toxins on female oogenesis and guide future research in this field

A Novel Label-Free Biosensor for Detection of HE4 in Urine Based on Localized Surface Plasmon Resonance and Protein G Directional Fixed

A non-invasive and more sensitive method for detection of HE4 is very important for the early screening and detection of ovarian carcinoma. In this study, we improved our previous localized surface plasmon resonance (LSPR) biosensor for detection of HE4 in urine to overcome disadvantages of conventional methods. Protein G directional fixed method was firstly used for LSPR biosensor to improved sensitivity, and standard HE4 and clinical samples were detected separately using this new biosensor. Compared to our previous LSPR biosensor, this new sensor was more sensitive, with other advantages as before. Under optimum conditions, this new biosensor could display a detection limit of 1 pM and wide dynamic range of 1 pM to 10,000 pM. This new biosensor was effective for detection of HE4 in urine of early ovarian cancer patients, without label and purification. To the best of our knowledge, this is first work to investigate LSPR biosensor for detection of tumor marker in urine, with great advantages and clinical application potentials

The survival outcome and complication of secondary cytoreductive surgery plus chemotherapy in recurrent ovarian cancer: a systematic review and meta-analysis

Abstract Objective The aim of this meta-analysis was to assess the effectiveness and safety of secondary cytoreductive surgery plus chemotherapy (SCS + CT) in recurrent ovarian cancer (ROC). Our secondary purpose was to analyze whether patients could benefit from complete resection. Methods We searched EMBASE, MEDLINE, the Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials, from inception to April 2021. We used appropriate scales to assess the risk of bias. Data from included studies that reported median PFS or OS were weighted by individual study sample size, and aggregated for meta-analysis. We calculated the pooled proportion of complications within 30 days after surgery. Results We identified 13 articles, including three RCTs and ten retrospective cohort studies. A total of 4572 patients were included, of which 916 patients achieved complete resection, and all patients were comparable at baseline. Compared with chemotherapy alone, SCS + CT significantly improved the PFS (HR = 0.54, 95% CI: 0.43–0.67) and OS (HR = 0.60, 95% CI: 0.44–0.81). Contrary to the results of cohort studies, the meta-analysis of RCTs showed that SCS + CT could not bring OS benefits (HR = 0.93, 95% CI: 0.66–1.3). The subgroup analysis showed the prognostic importance of complete resection. Compared with chemotherapy alone, complete resection was associated with longer PFS (HR = 0.53, 95% CI: 0.45–0.61) and OS (HR = 0.56, 95% CI: 0.39–0.81), while incomplete resection had no survival benefit. Additionally, complete resection could maximize survival benefit compared with incomplete resection (HR = 0.56, 95% CI: 0.46–0.69; HR = 0.61, 95% CI: 0.50–0.75). The pooled proportion for complications at 30 days was 21% (95% CI: 0.12–0.30), and there was no statistical difference in chemotherapy toxicity between the two groups. Conclusion The review indicated that SCS + CT based regimens was correlated with better clinical prognosis for patients with recurrent ovarian cancer, but the interpretation of OS should be cautious. The meta-analysis emphasizes the importance of complete resection, suggesting that the potential benefits of prolonging survival may outweigh the disadvantages of any short-term complications associated with surgery

The outcomes and quality of life of young patients undergoing adjuvant radiotherapy versus non-radiotherapy following surgery treating early FIGO stage cervical squamous cell cancer in southwestern China

Abstract Background: The incidence of cervical cancer in young women is rising, and squamous cell carcinoma makes up a great percentage of the histological types. The presence of aggressive pathologic risk factors following patients’ primary surgery may warrant the use of adjuvant radiotherapy. It is important to weigh up the risks and benefits of using adjuvant radiotherapy for each young patient so as to maximize their prognosis while minimizing the treatment-related morbidity. Methods: A retrospective study was performed. It consisted of 97 patients under 35 years old who were diagnosed with cervical squamous cell carcinoma and underwent treatment at West China Second University Hospital between December 2009 and January 2014. Five-year follow-up, prognostic risks, long-term radiation toxicity, female sexual function, and quality of life were investigated. Results: Adjuvant radiotherapy did improve the prognosis of young patients with lymph node metastases. However, there were few significant differences in progress-free survival and overall survival for the young patients without lymph node metastases following adjuvant radiotherapy. Besides, young patients who took radiotherapy exhibited greater intestinal dysfunction, more severe lower extremities edema, greater sexual dysfunction, and worse long-term quality of life. Conclusion: Young patients with early-stage cervical squamous cell carcinoma without lymph node metastases who have undergone the primary surgery should be counseled in detail before the decision to use adjuvant radiotherapy can be made. The counseling should emphasize not only the benefit that local recurrence rates can be reduced, but also the risks that treatment-related side effects could increase and lower QoL could occur

Correlation between heparanase gene polymorphism and susceptibility to endometrial cancer

Abstract Background Endometrial cancer is one of the three most common malignancies in the female genital tract. Previous studies have demonstrated the association between heparanase (HPSE, OMIM 604,724) single‐nucleotide polymorphism (SNP) and cancer risk in several cancers. However, its role in endometrial cancer remains unclear. The present study investigated the effects of HPSE SNPs on the susceptibility and clinicopathological parameters in patients with endometrial cancer. Methods HPSE SNPs of rs4693608 (G > A) and rs4364254 (C > T) were analyzed using polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) assay in 270 endometrial cancer patients and 320 healthy controls. Results The investigation indicated that the HPSE SNP rs4693608 with GG showed a protective effect from EC in both codominant (adjusted OR = 0.41, 95%CI = 0.21–0.81, p = .026) and recessive models (adjusted OR = 0.43, 95%CI = 0.22–0.82, p = .0076). No significant differences were found in the incidences of EC patients with the rs4364254 polymorphisms compared to controls. Moreover, a significantly increased distribution of A/A (rs4693608) was observed in patients with grade ≥ 2 (p = .03) and in patients with positive cervical invasion (p = .042) while patients with T/C (rs4364254) had lower tumor grade. Conclusion Our study suggested that HPSE SNP of rs4693608 correlated strongly with susceptibility to EC, and HPSE SNPs might be a potential biomarker for prognosis of endometrial cancer

Abnormal apoptosis of trophoblastic cells is related to the up-regulation of CYP11A gene in placenta of preeclampsia patients.

Abnormal placenta trophoblast proliferation and apoptosis is related to the pathogenesis of preeclampsia. Emerging evidence has also indicated that key pregnancy-associated hormones, such as hCG, progesterone, are found in high concentration at the maternal-fetal interface. The purpose of this study was to investigate the expression of CYP11A, a key enzyme in steroid hormone synthesis and metabolism, in normal pregnancy and severe preeclampsia placenta and to explore the underlying mechanism of the relationship between the altered CYP11A expression and onset of preeclampsia. Immunohistochemistry method was used to study the localization of CYP11A-encoded protein P450scc in the placenta; reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were used to examine CYP11A expression at mRNA and protein levels in patients with severe preeclampsia and normal placental tissue. CYP11A overexpression in trophoblastic cells was used to evaluate the effect on viability. TUNEL staining was used to determine whether overexpression of CYP11A could affect trophoblastic cell apoptosis. The results showed that CYP11A was selectively expressed in the cytoplasm of the placental trophoblastic cells. CYP11A expression were significantly increased in severe preeclampsia compared with normal pregnancy in both mRNA and protein levels. Multiple regression analysis indicated that CYP11A gene expression was positively correlated to ALT level and Plt, while negatively correlated to INR. Overexpression of CYP11A reduced trophoblastic cell proliferation and induced HTR8/SVneo cells apoptosis through activation of activated caspase-3 expression. These results suggest that abnormally high expression of CYP11A inhibits trophoblastic proliferation and increases apoptosis and therefore could be involved in the pathogenesis of preeclampsia

Inflammation Control and Tumor Growth Inhibition of Ovarian Cancer by Targeting Adhesion Molecules of E-Selectin

Objective: The aim is to use E-selectin-binding peptide (ESBP) to actively recognize E-selectin, so allowing a drug delivery system to actively recognize the cells and inhibit the tumor growth of ovarian cancer by targeting adhesion molecules of E-selectin. An ovarian-cancer-directed drug delivery system was designed based on the high affinity of E-selectin-binding peptide (ESBP) to E-selectin. The effects and mechanisms of ESBP-bovine serum albumin (BSA) polymerized nanoparticles were investigated. Methods: BSA polymerized nanoparticles (BSANPs) and ESBP-BSANPs-paclitaxel (PTX) were prepared and their characteristics were measured. The in vitro targetability and cytotoxicity of ESBP-BSANPs-PTX were evaluated through in vitro drug uptake and MTT experiments. The mechanisms of ESBP-BSANPs-PTX were investigated via apoptosis, wound healing and immunohistochemistry assays. The in vivo targeting properties and drug effects were observed in a mouse tumor-bearing model. Results: In vitro experiments revealed an increase in the uptake of ESBP-BSANPs-FITC. The cytotoxicity of ESBP-BSANPs-PTX in A2780/CP70, HUVEC, RAW264.7 and ID8 cells was higher than that of PTX alone. ESBP-BSANPs-PTX increased cell apoptosis in a dose-dependent manner and exhibited a greater ability to inhibit cell migration than BSANPs-PTX. In vivo experiments demonstrated the targetability and good effects of ESBP-BSANPs. Conclusions: ESBP-BSANPs-PTX improve PTX targetability, provide tumor-specific and potent therapeutic activities, and show promise for the development of agents in preclinical epithelial ovarian cancer