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   Table of Contents - Current issue
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January-March 2021
Volume 5 | Issue 1
Page Nos. 1-62

Online since Friday, April 16, 2021

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ORIGINAL ARTICLES  

Aspirin enhances the protective effect of progesterone on trophoblast cell from oxidative stress and apoptosis p. 1
Jia-Wei Shi, Hui-Li Yang, Zhen-Zhen Lai, Hui-Hui Shen, Lu-Yu Ruan, Yan Wang, Xue-Min Qiu, Feng Xie, Ming-Qing Li
DOI:10.4103/2096-2924.313686  
Objective: Clinically, low-dose aspirin and progesterone are frequently used to prevent pregnancy loss. We investigated the effect of these drugs on the biological behavior of human extravillous trophoblasts in vitro. Methods: HTR-8/SVneo cells were cultured in vitro and treated with different concentrations of aspirin and progesterone. The proliferation, invasion, and apoptosis of HTR-8/SVneo cells were assessed using a cell counting Kit-8 assay, Matrigel Transwell assay, and Hoechst staining, respectively. Reverse transcriptase polymerase chain reaction was used to verify the expression of related genes. Reactive oxygen species (ROS) levels were detected using the 2,7-dichlorofluorescin diacetate assay. Results: Low-dose aspirin alone, progesterone alone, or aspirin plus progesterone upregulated the proliferation and invasion and decreased the apoptosis of HTR-8/SVneo cells. Moreover, the expression of marker of proliferation Ki-67 (MKI67), matrix metalloproteinases 2 (MMP2), and MMP9 was increased. In addition, low-dose aspirin plus progesterone exerted stronger anti-apoptosis effects than low-dose aspirin and progesterone alone. Interestingly, aspirin upregulated the expression of progesterone receptor (PGR). Treatment with hydrogen peroxide (H2O2) promoted ROS production in HTR-8/SVneo cells; however, low-dose aspirin plus progesterone significantly restricted H2O2-mediated ROS production and apoptosis in HTR-8/SVneo cells. Conclusions: These data suggest that low-dose aspirin and progesterone promote proliferation and invasion and cooperatively reduce oxidative stress and apoptosis in trophoblasts in vitro. These results may provide an experimental basis for the combined application of aspirin and progesterone to prevent unexplained recurrent spontaneous miscarriage, especially in patients with trophoblast dysfunction.
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Effects of rosmarinic acid on DNA integrity and H19 differentially methylated region methylation levels in human sperm preserved by freeze-drying p. 9
Yi-Yu Wang, Wei-Jie Zhu
DOI:10.4103/2096-2924.309790  
Objective: To investigate the effects of rosmarinic acid (RA) on the DNA integrity and methylation levels of the H19 differentially methylated region (DMR) of freeze-dried human sperm after 1 week and 6 months of storage at 4°C. Methods: Semen samples from 15 healthy normospermic donors were used in this study. The samples were divided into five groups, including the control group with fresh sperm and four experimental groups with freeze-dried sperm (1-week storage with EGTA buffer solution, Group A; 1-week storage with EGTA buffer solution containing 105 μmol/L RA, Group B; 6-month storage with EGTA buffer solution, Group C; and 6-month storage with EGTA buffer solution containing 105 μmol/L RA, Group D). DNA integrity was evaluated using the sperm chromatin dispersion test. H19 DMR methylation levels were detected by bisulfite sequencing polymerase chain reaction. Results: After 1 week of storage, no differences in sperm DNA integrity were observed among Groups A, B, and controls (P > 0.05). After 6 months of storage, the sperm DNA integrity of Group D did not change significantly compared with that of the control group (P > 0.05), whereas that of Group C decreased significantly (P < 0.05). There were no differences in H19 DMR methylation levels among the five groups (P > 0.05). Conclusions: The DNA integrity of freeze-dried human sperm can be effectively protected by adding RA within 6 months, and the H19 DMR methylation level of human sperm can be maintained for 6 months after freeze-drying.
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Efficacy and safety of sanjiezhentong capsules, a traditional chinese patent medicine, on long-term management of endometriosis: A randomized controlled trial p. 15
Jing-Yao Ruan, Yun-Xi Zheng, Qi Tian, Jun-Ya Ke, Li Wang, Yan Du, Zhi-Ling Zhu, Xiao-Fang Yi, Cong-Jian Xu
DOI:10.4103/2096-2924.313687  
Objective: To compare the efficacy of the traditional Chinese medicine SanJieZhenTong (SJZT) capsules versus gonadotropin-releasing hormone analogs (GnRHa) or oral contraceptives (OCs) in the postoperative treatment of moderate-to-severe endometriosis. Methods: In this prospective clinical trial, women with stage III–IV endometriosis according to the revised American Fertility Society scoring system received three doses of GnRHa immediately after laparoscopic conservative surgery, followed by random assignment to receive treatment with SJZT, GnRHa, or OCs for another 6 months. The primary endpoint was 2-year recurrence, and the secondary endpoints were adverse events, changes in physical function, and quality of life (QoL). Recurrence was assessed using Kaplan–Meier curves and log-rank tests. Generalized estimating equations were used to determine the parameters of the secondary endpoints. Results: A total of 66 women were randomly assigned to the SJZT (n = 21), GnRHa (n = 21), and OCs (n = 24) groups. At a median follow-up of 22 months, no difference in recurrence was found (P = 0.72), with one (4.8%), two (9.5%), and one (4.2%) incidence in the SJZT, GnRHa, and OCs groups, respectively. Expectedly, the incidence of side effects such as hot flush, insomnia, and arthralgia in the SJZT and OCs groups was significantly lower than that in the GnRHa group (P = 0.00). In addition, the female sexual function index was significantly improved in the SJZT group, with a higher value than that in the GnRHa (odds ratio [OR] = 5.25, 95% confidence interval [CI]: 2.09–13.14, P = 0.00) and OCs (OR = 3.94, 95% CI: 1.58–9.83, P = 0.00) groups. Conclusions: SJZT showed more effective pain relief and QoL improvement in patients with moderate-to-severe endometriosis than GnRHa or OCs did. Fewer adverse events than those observed with other agents indicate that this alternative medicine, SJZT, could be a novel option for the long-term management of endometriosis.
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Risk of adverse perinatal outcomes and antenatal depression based on the zung self-rating depression scale p. 23
Xin-Ning Chen, Yao Hu, Wei-Hong Hu, Xian Xia, Xiao-Tian Li
DOI:10.4103/2096-2924.313683  
Objective: The aim of the study is to investigate the relationship between antenatal depression and adverse perinatal outcomes. Methods: This prospective cohort study enrolled pregnant women between gestational ages of 12–20 weeks to complete the Chinese version of the Zung Self-Rating Depression Scale (SDS) and followed them for delivery from September 2015 to September 2016. Participants were classified into mild, moderate, and severe depression groups according to the SDS scores. Logistic regression was performed to assess the association between antenatal depression and perinatal outcomes including preterm birth (PTB), cesarean section use, hypertension disorders, gestational diabetes, and thyroid diseases during pregnancy. An age-stratified analysis was performed. Results: A total of 4,663 pregnant women were analyzed. As a result, 13.8%, 1.7%, and 0.2% of women were classified as mild, moderate, and severe depression, respectively. Severely depressed mothers were at higher risk for PTB (adjusted odds ratio [OR] =11.31, 95% confidence interval [CI] 2.13–60.03), especially spontaneous PTB. Moderate-depressed women were at higher risk for hyperthyroidism during pregnancy (adjusted OR = 3.67, 95% CI 1.10–12.27), while women with mild depression tended to choose cesarean sections (OR = 1.24, 95% CI = 1.04–1.49). Age-stratified analysis indicated an elevated risk of adverse outcomes associated with depression in women aged <25 years, but the association was not significant. Conclusions: Antenatal depression was associated with PTB, hyperthyroidism, and cesarean use. Studies with large sample sizes should verify the relationship between PTB and antenatal depression to avoid casual events.
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REVIEW ARTICLES Top

Granulosa cell biomarkers to predict oocyte and embryo quality in assisted reproductive technology p. 30
Ruo-Han Huang, Wen-Hui Zhou
DOI:10.4103/2096-2924.313684  
With the development of human assisted reproductive technology (ART), an objective, accurate, and non-invasive method to assess the quality and viability of oocytes and embryos remains one of the most significant goals. Granulosa cells (GCs) play an essential role in oocyte development. GCs can differentiate into mural GCs (MGCs) and cumulus cells (CCs) under the influence of oocytes. MGCs promote the growth and development of follicles by secreting cytokines and steroid hormones. Simultaneously, CCs can form cumulus-oocyte complexes to communicate with oocytes through gap junctions and promote oocyte growth and maturation. Seeking suitable biomarkers in GCs provides a direction for the non-invasive assessment of oocyte and embryo abilities during ART procedures. To date, only a few studies have investigated potentially effective GC biomarkers during ART processes, such as the apoptosis of GCs, transcriptomic characteristics of GCs, quality and quantity of mitochondria in GCs, and telomere length of such cells. These are potential reference indices for screening high-quality oocytes and embryos. Independent studies on MGCs and CCs can provide more effective results. Although there is scope for optimization and improvement, the results have become increasingly accurate with the constant advances in technology. Due to the heterogeneity of the study population and technical limitations, clinical tests for GCs cannot be performed as part of routine tests, but their prospects are promising. This article reviews the biomarkers that have been studied in MGCs and CCs.
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Effects of copper-containing intrauterine devices on the endometrium p. 38
Jia-Hui Che, Xiao-Ying Yao
DOI:10.4103/2096-2924.309791  
The use of copper-containing intrauterine devices (Cu-IUDs) is a safe, effective, and long-term contraceptive method. Here, we review the effects of Cu-IUDs on subsequent pregnancy and the morphology, local coagulation function, sensitivity to estrogen and progesterone, cell proliferation, and immune response of the endometrium. Studies on the morphology of endometrium indicate that the use of Cu-IUDs can affect the number and binding capacity of estrogen and progesterone receptors in the endometrium and reduce the response of the endometrium to estrogen and progesterone. The use of Cu-IUDs can also affect the proliferation of endometrial cells, suggesting that the aseptic inflammation caused by Cu-IUDs may differ from chronic infectious or noninfectious inflammation; this highlights that the use of Cu-IUDs provides protection against endometrial proliferative diseases. The use of Cu-IUDs increases local endometrial angiogenesis, bleeding tendency, and fibrinolytic activity, which can result in prolonged menstruation or abnormal uterine bleeding. Additionally, the use of Cu-IUDs can cause the infiltration of numerous lymphocytes, monocytes, macrophages, and other inflammatory cells around the endometrial gland and changes in endometrial immune function, immune cell function, and the number and type of immune molecules. Cu-IUD-induced decidual injury significantly increases the invasiveness of trophoblasts, further affecting the aberrant expression of their growth-, angiogenesis-, and invasion-related factors and improving the formation of the placenta. Moreover, the endometrial damage caused by Cu-IUD placement before embryo transfer can improve both clinical pregnancy and live birth rates; however, specific changes in the immune system after Cu-IUD use as well as its effects on future pregnancies require further investigation.
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Fertility preservation in cancer patients p. 44
Yuan-Xue Jing, Li-Li Zhang, Hong-Xing Li, Feng Yue, Nai Hui Wang, Shi-Long Xue, Yi-Qing Wang, Xue-Hong Zhang
DOI:10.4103/2096-2924.309789  
Traditional radiotherapy and chemotherapy often cause irreversible damage to the fertility and endocrine function of cancer patients. The current methods of fertility preservation include freezing the sperms of adult and adolescent males after puberty; freezing the embryos, oocytes, and ovarian tissue of females; and drug intervention and fertility preservation surgery. This article reviews fertility preservation in cancer patients with respect to current methods, indications, and some more recently developed methods that remain under investigation.
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Clinical application potential of umbilical cord mesenchymal stem cells in chemotherapeutic ovarian failure p. 55
Zi-Jie Fu, Xiao-Dong Li, Da-Wei Wei, Xue-Lei Ding
DOI:10.4103/2096-2924.313685  
Chemotherapy is often used for female malignancies, but it can increase the risk of premature ovarian failure in women of reproductive age through different mechanisms. Therefore, how to protect ovarian function and preserve fertility has attracted great attention of oncologists and gynecologists. Recently, umbilical cord mesenchymal stem cells (UCMSCs) have been extensively studied in the field of regenerative medicine. Compared with mesenchymal stem cells (MSCs) from other sources, UCMSCs have a broader application potential due to their properties of lower immunogenicity, fewer ethical issues, and non-invasive collection. Paracrine is one of the most important therapeutic mechanisms of UCMSCs, which can exert anti-inflammatory, anti-fibrosis, anti-oxidative stress, immune regulation, and other therapeutic effects. Studies in animal models have shown that UCMSCs can restore ovarian function after chemotherapy injury. However, most of the relevant researches are still in the preclinical stage. In this article, the mechanism of chemotherapy-induced ovarian failure will be overviewed, and the clinical application potential of UCMSCs in chemotherapeutic ovarian injury will be discussed.
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