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EXPERT REVIEWS
Single-cell RNA expression profiling of ACE2 and AXL in the human maternal–Fetal interface
Qing-Liang Zheng, Tao Duan, Li-Ping Jin
January-March 2020, 4(1):7-10
DOI:10.4103/2096-2924.278679  
2019 novel coronavirus disease has resulted in thousands of critically ill patients in China, which is a serious threat to people's life and health. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was reported to share the same receptor, angiotensin-converting enzyme 2 (ACE2), with SARS-CoV. Here, based on the public single-cell RNA-sequencing database, we analyzed the mRNA expression profile of putative receptor ACE2 and AXL receptor tyrosine kinase (AXL) in the early maternal–fetal interface. The result indicates that the ACE2 has very low expression in the different cell types of early maternal–fetal interface, except slightly high in decidual perivascular cells cluster 1 (PV1). Interestingly, we found that the Zika virus (ZIKV) receptor AXL expression is concentrated in perivascular cells and stromal cells, indicating that there are relatively more AXL-expressing cells in the early maternal–fetal interface. This study provides a possible infection route and mechanism for the SARS-CoV-2- or ZIKV-infected mother-to-fetus transmission disease, which could be informative for future therapeutic strategy development.
  9 5,648 376
REVIEW ARTICLES
Estrogen Biosynthesis and Its Regulation in Endometriosis
Qiu-Ming Qi, Sun-Wei Guo, Xi-Shi Liu
January-March 2017, 1(1):55-61
DOI:10.4103/2096-2924.210698  
Endometriosis is a common benign gynecological disorder with an enigmatic etiology and pathogenesis. It affects approximately 10% women of reproductive age. Although its etiology and pathogenesis remain poorly understood, it is characterized by the elevated local production of estrogen in the endometriotic tissues. In this paper, we review the mechanisms of estrogen biosynthesis and its regulation in endometriosis.
  3 2,668 316
ORIGINAL ARTICLES
Analysis of the Fragile X Mental Retardation 1 Premutation in Han Chinese Women Presenting with Primary Ovarian Insufficiency
Qing Chen, Qi-Qi Wang, Bao-Zhu Cai, Xiao-Jun Ren, Feng Zhang, Xiao-Jin Zhang
January-March 2017, 1(1):9-12
DOI:10.4103/2096-2924.210692  
Background: The aim of this study is to investigate the prevalence of the fragile X mental retardation 1 (FMR1) gene premutation in Han Chinese women with primary ovarian insufficiency (POI) using a rapid and cost-effective method. Methods: A total of 153 Han Chinese women with sporadic POI were systematically analyzed for trinucleotide repeats within the FMR1 gene. We employed an improved strategy to screen for cytosine-guanine-guanine repeats in the 5' untranslated region of the FMR1 gene. Before using the previously reported FragilEase polymerase chain reaction (PCR) method for premutation identification, we developed a new cost-effective PCR-based method to exclude most of the normal allele carriers during the initial screening stage. Results: In our initial screening, 62.1% of women with POI were found to carry heterozygous normal alleles of FMR1, which were recognized by our sensitive and cost-effective method. The remaining women were further screened for the presence of the FMR1 premutation. We identified a Han Chinese woman with a premutation allele of FMR1 out of 153 sporadic POI women (0.7%). Conclusions: The frequent FMR1 premutation in Caucasian individuals with POI may not be a common genetic cause of sporadic POI in the Han Chinese population.
  2 1,765 278
Influence of growth hormone supplementation in patients with thin endometrium undergoing frozen embryo transfer
Jun-Yi Yang, He Li, Nan Lu, Lu Li, Xiao-Xi Sun
January-March 2019, 3(1):49-53
DOI:10.4103/2096-2924.255983  
Objective: To evaluate the effect of recombinant human growth hormone (rhGH) supplementation during hormone-replacement therapy and frozen-thawed embryo transfer (FET) in patients with thin endometrium. Methods: A retrospective research was conducted on 225 patients, who underwent artificial cycle FET in Shanghai, China, between January 2016 and November 2017. Data from 245 FET cycles were analyzed, of which 184 cycles received rhGH (GH group) and 61 did not (control group). Results: Clinical pregnancy and implantation rates were significantly higher in the GH group than those in the control group (64.7% vs. 49.2%, P = 0.032; 44.8% vs. 32.8%, P = 0.019, respectively). After logistic regression analysis, rhGH was considered the only significant variable that influenced clinical pregnancy rate, increasing it by 1.89-fold. On the other hand, the presence of rhGH did not seem to affect the early pregnancy loss. Conclusions: Our results indicated that simultaneous addition of rhGH could improve clinical outcomes of FET in patients with thin endometrium, particularly in patients between 30 and 34 years of age.
  2 1,460 210
Activated platelets induce hypoxia-inducible factor-1α expression likely through transforming growth factor-β1 in human endometrial stromal cells
Qiu-Ming Qi, Sun-Wei Guo, Xi-Shi Liu
April-June 2019, 3(2):69-76
DOI:10.4103/2096-2924.262390  
Objective: Endometriosis is a common gynecological disease with an enigmatic pathogenesis. Recent studies suggest that the behavior of normal endometrial stromal cells can dramatically change under hypoxic conditions, which effectively turns them into endometriotic stromal cells. Because menstrual debris is not only hypoxic but may also contain platelet aggregates, at present, we aimed to approve that activated platelets could induce hypoxia-inducible factor-1α (HIF-1α) expression in endometrial stromal cells, signaling the presence of hypoxia. Methods: We evaluated the gene and protein expression levels of HIF-1α and its target gene erythropoietin (EPO) in both human endometriotic stromal cells (HESCs) and a human endometrial stromal cell line (ESCL) cocultured with or without activated platelets for 48 h. Results: We found that the gene and protein expression levels of HIF-1α and EPO in both HESC and ESCL were significantly increased after coculture with activated platelets. We also found that neutralization of transforming growth factor-β1 completely abolishes this induction. Conclusions: Platelets can induce a hypoxic state in endometrial and endometriotic stromal cells, resulting in increased angiogenesis, as well as enhanced survival and proliferation. In conjunction with other roles that platelets play in the development of endometriosis, our findings further highlight the important roles of platelets in the development and initiation of endometriosis, shedding new light into the etiology of endometriosis.
  2 791 132
REVIEW ARTICLES
Spermatogonial Stem Cell Self - renewal and Differentiation
Li-Huan Cao, Qiao-Li Zhang, Xin-Hua Lin
July-September 2017, 1(3):171-178
DOI:10.4103/2096-2924.224213  
Mammalian spermatogenesis is a complicated and precisely controlled process that requires spermatogonial stem cells (SSCs). SSCs maintain the stem cell pool, balance self-renewal–commitment with differentiation, and produce millions of sperm daily. Self-renewal and differentiation are controlled by intrinsic factors within SSCs and extrinsic factors from the “niche.” In this review, we discuss the biology of SSCs and the factors regulating their self-renewal and differentiation.
  2 1,625 250
Effects of Mycoestrogens on Female Reproduction
Christian Lee Andersen, Fei Zhao, Xiao-Qin Ye
January-March 2018, 2(1):52-58
DOI:10.4103/2096-2924.232875  
Zearalenone (ZEA) is produced by Fusarium species and a common contaminant in food. ZEA and its metabolites, α- and β-zearalenol, α- and β-zearalanol, and zearalanone, are mycoestrogens that can interfere with estrogen signaling. High levels of mycoestrogens reduced female fertility in farm animals and rodents, in which adverse effects of mycoestrogens on major events in female reproduction, including ovarian folliculogenesis, ovulation, ovarian steroidogenesis, fertilization, preimplantation embryo development and transport, embryo implantation, placentation, parturition, and lactation, have been reported in different experimental settings. Here, we review the in vivo effects of mycoestrogens on the main events in female reproduction.
  2 1,579 169
CASE REPORTS
Infertility due to lack of zona pellucida caused by a compound heterozygous mutation in ZP1 gene
Zheng Zhang, Tao Shangguan, Yu-Yan Li, Wei He
July-September 2018, 2(3):183-186
DOI:10.4103/2096-2924.248486  
Lack of the zona pellucida (ZP) is one of the manifestations of an oocyte maturation disorder. In recent years, genetic factors have attracted much attention as a possible cause of ZP anomalies. In this study, we report a form of primary infertility characterized by abnormal eggs that lack the ZP, which resulted from a compound heterozygous autosomal recessive mutation in ZP1. This compound heterozygous mutation has been reported for the first time, and our results may expand the spectrum of known mutations in ZP genes and provide evidence of oocyte maturation disorders during genetic counseling.
  1 903 137
ORIGINAL ARTICLES
Cytogenetic analysis for fetal chromosomal abnormalities by amniocentesis: Review of over 40,000 consecutive cases in a single center
Shuo Zhang, Ming Yin, Jian-Zhong Xu, Cai-Xia Lei, Jun-Ping Wu, Xiao-Xi Sun, Yue-Ping Zhang
April-June 2017, 1(2):84-88
DOI:10.4103/2096-2924.216865  
Background: The aim of this study was to retrospectively investigate the 18-year experience of prenatal diagnosis of fetal karyotype analysis by amniocentesis. Methods: In this study, the authors reviewed the cytogenetic results of 40,208 fetuses with indications for amniocentesis enrolled from December 1998 to December 2015. Cytogenetic analysis of amniotic fluid was performed in all these pregnancies. Eight indications for amniocentesis were included. The detection rate and distribution of abnormal karyotypes were observed in each indication. Results: Among all these samples, abnormal maternal serum screening test was the most common indication for amniocentesis (17,536, 43.67%), followed by advanced maternal age (11,734, 29.18%), abnormal ultrasound findings (5,328, 13.25%), and required by pregnant women (2,557, 6.36%). Chromosomal abnormality was detected in 1,349 (3.36%) samples, 63.01% of the abnormalities were numerical, and 36.99% were structural. The detection rates of abnormal karyotype were 55.60% in one of the couple with chromosomal abnormality, 4.43% in the pregnant women with pathological ultrasound finding, 2.83% in the pregnant women with advanced age, and 2.73% in women with abnormal maternal serum screening tests. Of the fetuses with chromosome aberrations, 680 (50.41%) had trisomy 13, trisomy 18, or trisomy 21, and 138 (10.23%) had sex chromosome disorder. The other 531 abnormal samples included translocation, mosaicism, inversion, deletion, addition, and marker chromosome. Conclusions: Cytogenetic analysis, therefore, remained an effective approach to decrease the birth defects of fetuses with indications for amniocentesis. These results could provide meaningful suggestions for clinical genetic consulting and prenatal diagnosis.
  1 2,034 256
The GLI2 Missense Variant rs3738880 Significantly Increases the Risk of Neural Tube Defects in the Han Chinese Population
Shu-Xia Chen, Hui-Li Li, Cai-Hua Li, Ting Zhang, Hong-Yan Wang, Xue-Yan Yang
July-September 2017, 1(3):127-132
DOI:10.4103/2096-2924.224214  
Background: The sonic hedgehog (SHH) pathway is an important signaling pathway for neural tube closure. GLI family zinc finger 2 (GLI2) is the major activation mediator of the SHH pathway; however, no single-nucleotide polymorphisms (SNPs) in GLI2 have been reported to be associated with human neural tube defects (NTDs) to date. Here, we evaluated a mutation in GLI2 in the Han Chinese population. Methods: We used SNPscan to genotype rs3738880 in the GLI2 coding region. We then investigated the function of this gene by Western blotting and dual-luciferase assays. Results: In this study, we found that the GLI2 missense variant rs3738880 significantly increased the risk of NTDs in the Han Chinese population via association studies in a cohort of 254 patients and 277 controls from Shanxi Province (odds ratio [OR] = 1.89, 95% confidence interval [CI] = 1.28–2.80, P = 0.0012). Additional stratified analyses demonstrated that rs3738880 was significantly related to spina bifida (114 cases, OR = 2.01, 95% CI = 1.19–3.38, P = 0.0067). Functional analysis revealed that rs3738880 did not affect GLI2 protein stability and significantly increased SHH activity because of the introduction of a potential phosphorylation site in GLI2. Conclusion: rs3738880 was a risk factor for NTDs in the Han Chinese population.
  1 1,519 165
Effects of cryopreservation on human sperm glycocalyx
Yan-Cheng Wu, Ai-Jie Xin, Hui Lu, Hua Diao, Li Cheng, Yi-Hua Gu, Bin Wu, Sheng-Ce Tao, Zheng Li, Hui-Juan Shi, Yong-Lian Zhang
October-December 2017, 1(4):233-238
DOI:10.4103/2096-2924.224914  
Background: To study the effects of cryopreservation on human sperm glycocalyx. Methods: The lectin binding profilings of sperm after freeze-thaw were compared by lectin microarray. Results: CryoSperm™ and direct fumigation were confirmed to be the optimized cryoprotectant and method by comparing the sperm recovery rate. In 91 lectins, 33 lectins were significantly changed after sperm cryopreservation. Among them, 9 lectins greatly decreased and 24 lectins mainly increased. The binding signals of MAA, PSA, ABA, and AIA were verified by FACS, and the results were consistent with that of lectin microarray. Conclusions: Sperm glycocalyx had significant changes after cryopreservation. The sialic acid, playing an important role in protecting sperm, was greatly lost, which exposed the inner carbohydrates. Thus, the glycocalyx damage due to the cryopreservation might be one of the reasons for low sperm fertility.
  1 1,442 201
Galectin-9 Promotes Human Trophoblast Cell Invasion through Matrix Metalloproteinase-2 and p38 Signaling Pathway
Feng-Run Sun, Chun-Qing Chen, Min Yu, Song-Cun Wang, Da-Jin Li, Mei-Rong Du
January-March 2018, 2(1):1-7
DOI:10.4103/2096-2924.232880  
Objective: Adequate extravillous trophoblast (EVT) invasion plays a crucial role in the establishment of successful pregnancy. Insufficient trophoblast migration and invasion can result in defective placentation, which is associated with a number of clinical pathological conditions of pregnancy including spontaneous abortion and preeclampsia. Galectin-9 (Gal-9) has a wide variety of regulatory functions in innate and adaptive immunity during infection, tumor growth, and organ transplantation. Methods: We utilized immortalized human first-trimester EVT cells (HTR8/SVneo) for our functional study. We examined the effects of Gal-9 on viability, proliferation, and invasion of HTR8/SVneo cells, as well as on matrix metalloproteinase-2 (MMP-2) production in HTR8/SVneo cells. Furthermore, we observed the effects of different MAPK-signaling pathway inhibitors on the stimulatory functions of Gal-9 on HTR8/SVneo cells' invasion. Results: We verified the secretion of Gal-9 by trophoblasts and detected a correlation between low levels of Gal-9 and spontaneous abortion. Gal-9 promoted the invasion of HTR8/SVneo cells through its interaction with Tim-3, not CD44, and subsequently increased MMP-2 production. Blockade of p38 signaling pathway inhibited Gal-9 activities in HTR8/SVneo cells. Conclusion: Gal-9 promotes human trophoblast cell invasion through MMP-2 and p38 signaling pathway in a Tim-3-dependent manner.
  1 1,838 251
Effect of Metformin-Induced Stimulation on the Expression of Insulin Receptor Substrate 1 through Negative Regulation of P70S6k
Hui-Ming Ma, Dong-Mei Chen, Li Xiang, Chao-Qun Liu, Qiao-Ni Hou, Yan-Tao He, Cheng Xin, Yong-Fang Zhang, Xiu-Ying Pei, Yan-Rong Wang, Xian Xu
January-March 2018, 2(1):15-20
DOI:10.4103/2096-2924.232874  
Objective: The aim is to study the effects of metformin on the expression of 70 kDa ribosomal protein S6 kinase (P70S6k), insulin receptor substrate 1 (IRS-1), and IRS-1Ser307 phosphorylation in human luteinized granulosa cells. Methods: Granulosa cells in the experimental group were cultured in M199 medium containing 0.1 mmol/L metformin for 24 h and those in control group were cultured in M199 medium. The expression levels of P70S6k and IRS-1 mRNA were detected by reverse-transcriptiom polymerase chain reaction (RT-PCR) and real-time PCR. P70S6k, IRS-1, p-ser307-IRS-1, and p-thr389-P70S6k protein expression levels were detected by immunofluorescence and western blotting. Results: P70S6k mRNA level was higher and IRS-1 was significantly lower in the experimental group than those in the control group. IRS-1 and p-ser307-IRS-1 were expressed in cell plasma, and P70S6k and p-thr389-P70S6k were expressed in cell nucleus. The results of Western blot analysis indicated that the expression levels of P70S6k, p-thr389-P70S6k, IRS-1, and p-ser307-IRS-1 proteins had significant difference between the experimental group and the control group. Compared to the control group, the relative intensity illustrated that the expression levels of P70S6K and p-thr389-P70S6k significantly increased in the experimental group; however, those of IRS-1 and p-ser307-IRS-1 proteins significantly decreased. Conclusion: Metformin can inhibit the P70S6k mRNA and protein expression levels in the granulosa cells and improve insulin sensitivity by regulating IRS-1 expression through Akt/P70S6k/IRS-1-dependent pathway.
  1 1,509 193
Distinctive genes involved in steroidogenesis associated with follicular abnormal development in polycystic ovary syndrome model
Kai-Lun Yu, Xiu-Li Zhang, Xue-Mei Tan, Meng-Meng Ji, Yao Chen, Man-Man Liu, Zeng-Li Yu
July-September 2019, 3(3):141-147
DOI:10.4103/2096-2924.268157  
Objective: Polycystic ovary syndrome (PCOS), a heterogeneous endocrine disorder, affects female reproductive function, but its etiology has not been elucidated. In this study, we analyzed the differential genes related to ovarian steroid biosynthesis in patients with PCOS, to explore the mechanism of PCOS. Methods: The GSE59456 data were downloaded from the Gene Expression Omnibus database. We identified differentially expressed genes (DEGs) in ovaries between the female Sprague–Dawley rats those implanted with 5α-dehydrotestestrone (DHT) and those in control (CTL, implanted with empty capsule). Gene ontology, pathway enrichment analysis, and protein–protein interaction (PPI) network construction were subsequently performed. Results: In total, 530 upregulated DEGs and 522 downregulated DEGs were identified. The identified DEGs were mostly associated with steroid biosynthesis. In the PPI network, the module M1 was mainly related to steroid biosynthesis, and five genes (Hsd17b7, Tm7sf2, Idi1, Msmo1, and Sqle) of the module M1 were from the aforementioned group of upregulated genes. Furthermore, the 19 DEGs (Idi1, Cga, C1qb, Thy1, Gpx1, Ctss, Lpl, A2m, Cited2, Plppr4, Prkar2b, Slc44a1, Inha, Rbp4, Pla2g2a, Gata4, Fabp3, Cpa2, and Cpa1) between DHT and CTL groups were associated with the process of the transformation of primordial follicles to primary follicles. Conclusions: These DEGs, such as Hsd17b7, Tm7sf2, Idi1, Msmo1, Sqle, Rbp4, Gata4, Inha, and Cited2, may be used to elucidate the etiology of PCOS, which may provide new insights into the exploration of pathological mechanism and biomarkers for polycystic ovary.
  1 1,443 332
Gene Expression Pattern of Histone Acetylation Enzymes Changed in the Hypothalamus of Middle-Aged Female Rats: A Putative Mechanism for Female Reproductive Aging
Wen Xu, Na Zhang, Li-Sha Li, Yan Wang, Lin Wang, Mei-Rong Du, Da-Jin Li, Yan Sun
April-June 2018, 2(2):65-73
DOI:10.4103/2096-2924.242756  
Objective: Female reproductive aging is characterized by reduced responsiveness of the hypothalamus to E2-positive feedback, which can result in alterations of gene expression and luteinizing hormone (LH) surge dysfunction. We hypothesize that age-related changes in E2-responsive gene expression are due to altered histone acetylation by histone deacetylases (HDACs) or estrogen receptor-alpha (ERα) coactivators with histone acetyltransferase (HAT) activity. Methods: In the present study, young and middle-aged female rats were ovariectomized (OVX) and treated with E2 or oil once per day for 2 days. At the time of the expected LH surge, the anterior and posterior hypothalami were dissected, and gene expression of 11 HDACs and 4 ERα coactivators with HAT activity was measured using real-time polymerase chain reaction. Results: In the anterior hypothalamus, age affected the gene expression of 3 HDACs (Hdac3, Hdac5, and Hdac11) and 2 ERα coactivators (Src2 and Crebbp). E2 treatment significantly decreased mRNA levels of 4 HDACs (Hdac4, Hdac5, Hdac10, and Hdac11) and 2 ERα coactivators (Src2 and Crebbp) in young females (3–4 months). However, none of the genes responded to E2 in the middle-aged females (9–11 months), except Hdac10. In the posterior hypothalamus, age influenced Hdac5 and Src1 mRNA expression. E2 treatment increased Hdac4 and Crebbp mRNA levels in the young but not middle-aged females. Conclusions: These data suggest that E2 regulates HDACs and ERα coactivators with HAT activity in an age- and E2-dependent manner, which may contribute to the age-related gene expression changes on the day of LH surge in female reproductive aging.
  1 1,367 192
LncRNA4667 is dispensable for spermatogenesis and fertility in mice
Yu-Bing Dai, Yu Lin, Ning Song, Fei Sun
January-March 2019, 3(1):18-23
DOI:10.4103/2096-2924.255985  
Objective: Spermatogenesis is a complex process which is of vital importance for sexual reproduction. In many studies of spermatogenesis, the mRNAs, protein-coding genes, as well as small noncoding RNAs (ncRNAs) have been well characterized. However, there remain numerous questions despite previously characterized molecular mechanisms. Long ncRNAs (lncRNAs) are a relatively new addition to our knowledge of ncRNAs. Limited studies have examined the function of lncRNAs in spermatogenesis. Therefore, we selected a testis-specific lncRNA, lncRNA4667, to analyze its potential role in spermatogenesis and male fertility. Methods: In situ hybridization and quantitative reverse transcription polymerase chain reaction analyses were used to confirm testis-specific expression of lncRNA4667. LncRNA4667 knockout mice were generated using CRISPR/Cas9 technology. Histology, sperm counts, sperm motility, body parameters, and fertility were compared between wild-type and knockout mice (n = 8/group). Results: Expression analysis showed that lncRNA4667 was testis specific and localized to round spermatids in seminiferous tubules of adult mouse testes. Mice homozygous for a null mutation of lncRNA4667 displayed normal spermatogenesis and fertility compared with wild-type mice. Conclusions: These data indicate that lncRNA4667 is dispensable for spermatogenesis and fertility in mice, and the localization of lncRNA4667 makes it a useful marker for the identification of round spermatids in mice.
  1 1,228 203
Lin28B expression in reduced uterine perfusion pressure rat model
Yun Yang, Jia-Po Li, Yue Bian, Gui-Yu Song, Yuan-Yuan Li, Dong-Ying Zheng, Ling Huang, Chong Qiao
January-March 2019, 3(1):36-41
DOI:10.4103/2096-2924.255987  
Objective: Preeclampsia (PE) is a serious complication of pregnancy. Placental ischemia could be an initiating event, but the molecular mechanisms underlying PE are unclear. Lin28B, a paralog of Lin28 RNA-binding protein, is predominantly expressed in human placenta, and decreased Lin28B expression may play a role in PE by reducing trophoblast invasion. The current study was intended to verify whether Lin28B plays a role in the pathogenesis of PE in rat model for reduced uterine perfusion pressure (RUPP). Methods: We used RUPP rat model. The changes in blood pressure, 24-h urine protein excretion, and fetal development in RUPP rats were recorded and compared to those of normal pregnant (NP) rats. Furthermore, the expression of Lin28B mRNA and protein in placenta was determined using quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry. Results: The blood pressure, 24-h urine protein excretion, and embryo absorption rate were significantly increased in RUPP rats on the 20th day of gestational period compared with the NP rats (P < 0.001). However, there was no difference in the weight of placenta in RUPP versus NP rats (P > 0.05). The expression levels of Lin28B mRNA and protein in the placenta of RUPP rats were also significantly decreased in comparison to NP rats (P < 0.001). Conclusion: Our results show that the expression of Lin28B in the placenta of RUPP rats is different from that in NP rats, thus suggesting a role of Lin28B in the pathogenesis of preeclampsia.
  1 750 110
REVIEW ARTICLES
Modern clinical application of Ding 1541
Lin Huang, Yan-Lin Liang, Hai-Bin Wang
July-September 2018, 2(3):178-182
DOI:10.4103/2096-2924.248482  
For hundreds of years, Ding 1541 is used in traditional Chinese medicine (TCM) for the treatment of numerous ailments, including qi and blood stasis-related disorders. It showed good efficacy in relieving irregular menstruation, dysmenorrhea, metrorrhagia, and metrostaxis. Now, Ding 1541 has been widely used in various conditions, including primary dysmenorrhea, menstrual disorder, endometriosis, infertility, premenopausal syndrome, polycystic ovary syndrome, and premature ovarian failure. Compared with western medicine treatment, Ding 1541 has showed some advantages. In this review, we tried to summarize the underlying mechanisms for Ding 1541's effects. We collected clinical data and briefly analyzed these diseases based on the theories of TCM and the pathology. These data suggested that the underlying mechanisms of Ding 1541 involved increasing uterine blood supply, decreasing menstrual blood prostaglandin F2α level, improving the immune, and enhancing the function of the hypothalamus-pituitary-ovary, etc.
  1 913 87
Mitochondrial Dysfunction and Age - related Oocyte Quality
Han Li, Ri-Cheng Chian
January-March 2017, 1(1):45-54
DOI:10.4103/2096-2924.210693  
Fertility disorders have become a growing problem worldwide. It is well known that female fertility decreases with age, previous studies suggested that the age-related decline in female fertility potential was largely due to decrease in oocyte quality and mitochondrial dysfunction. Mitochondria play a crucial role during the process of oocyte maturation. Mitochondrial genetic, numerical and structural defects occur in oocyte aging process, mitochondrial abnormalities are believed to contribute to age-related infertility. Improvement of the mitochondrial function can lead to better fertility outcomes, and application of mitochondria replacement strategy or mitochondrial transfer to age-related infertility will be possible in the future. This review paper, we are trying to discuss current understanding about age-related changes in oocyte quality and mitochondrial dysfunction.
  1 2,771 476
Developmental aspect of decidual patterning
Chan Zhou, Hai-Li Bao, Shuang-Bo Kong, Jin-Hua Lu, Hai-Bin Wang
April-June 2017, 1(2):100-114
DOI:10.4103/2096-2924.216864  
In clinical practice, early pregnancy loss has afflicted approximately 15%–25% women of reproductive age worldwide, which is partially attributed to defects associated with the endometrium. During pregnancy, the endometrial stromal cells experience remarkable tissue remodeling and transformation, termed as decidualization, to support embryonic development, placental formation, and the maintenance of normal pregnancy in both mice and human. During this process, a series of dynamic developmental events, including rapid stromal proliferation, increased stromal cell size, enhanced angiogenesis, taken place in a highly-ordered manner under the precise regulation of steroid hormones. Meanwhile, diverse molecules exhibit spatiotemporal-specific expression pattern, implying their unique roles in decidual development. To achieve a more comprehensive understanding of these biological events and explore the underlying causes of early pregnancy disorders, this review emphasizes on the detailed developmental progression of decidual transformation and patterning as well as related pregnancy complications at the early stage of pregnancy.
  1 2,824 284
Advances in the treatment of recurrent implantation failure
Feng Guo, Ming-Juan Zhou, Ai-Jun Zhang
April-June 2017, 1(2):123-126
DOI:10.4103/2096-2924.216860  
Recurrent implantation failure (RIF) is a syndrome of complex etiology. Excluding the involvement of embryonic factors, RIF is characterized by women aged ≤40 years who fail to achieve clinical pregnancy after at least four high-quality embryos transfer in a minimum of three fresh or frozen cycles. However, current methods in the treatment of RIF are controversial. So far, there are no reports of any criteria or guidelines, and the mechanism of RIF is still not clear. Herein, we summarize the pathogenesis of RIF and highlight recent methods in its treatment, to provide reference for the basic and clinical research on RIF.
  1 6,697 768
Cumulus Cells and their Associations with Immune Functions
Ping Xia, Clement Leung-Kwok Chan
January-March 2018, 2(1):59-63
DOI:10.4103/2096-2924.232877  
The recent progress in the association of cumulus cells with immune functions is a largely ignored area. With over 350 million new sexually transmitted infections occurring annually in adults of reproductive age, we feel the need to explore more about how the cumulus cells defend themselves and protect the oocytes during the development through the ovulation period. Application of assisted reproductive technologies allows scientists to study and better understand cumulus cells. There are still many immune factors to be taken into consideration to optimize the oocyte quality besides ovarian stimulations. The objective of this review is to summarize the key elements of cumulus cells and their association with the immune function.
  1 1,323 162
Predictive modeling in reproductive medicine
Jing Lin, Xiao-Xi Sun
October-December 2018, 2(4):224-229
DOI:10.4103/2096-2924.249888  
The accurate prediction of fertility outcomes is an extremely interesting and challenging task in reproductive medicine. Efforts in this area focus on classic statistical models and newer technologies, including machine learning. The modeling process has three steps, namely, data preparation, model selection and data fitting, and model validation. Here, we present a review of studies on these methods of fertility prediction. Various databases were searched using relevant keywords. Original studies with full-text available on this topic were included for review. Earlier studies explored prediction models for spontaneous pregnancy prognosis, reproductive outcomes after intrauterine insemination and in vitro fertilization, and implantation potential based on embryo morphology and morphokinetic data. Future directions for predictive modeling in reproductive medicine include solving problems presented by big data, identifying novel informative features, balancing predictive power and result interpretability, and validating models with gold-standard study designs.
  1 1,416 223
In Vitro growth of human ovarian follicles for fertility preservation
Diego Marin, Min Yang, Tianren Wang
October-December 2018, 2(4):230-236
DOI:10.4103/2096-2924.249892  
Young female cancer survival rates significantly increased due to the great progress of cancer therapy. In fact, cryostorage and transplantation of ovarian tissue have already resulted in the birth of healthy babies. Follicle in vitro growth (IVG) has the great potential of restoring fertility by achieving functional oocytes from the most immature stages to maturation. This is suitable for a wide range of patients, from pubertal to perimenopause women. Notable achievements have been achieved in human follicle IVG in the past decade. Mature oocytes have been successfully collected from long-term sequential follicle IVG. However, it is still a major challenge to establish a stable and efficient follicle IVG system able to generate mature and competent oocytes. Hereby, we review the approaches being taken so far using ovarian tissue to support follicle growth at different stages in vitro.
  1 1,299 214
Strategies of infertility treatment with human immature oocytes
Ri-Cheng Chian, Ling Wang, Zhi-Yong Yang
October-December 2018, 2(4):237-248
DOI:10.4103/2096-2924.249885  
Human immature oocytes can be matured in vitro following culture. In vitro maturation (IVM) refers to maturation in culture of immature oocytes at different stages that may or may not have been exposed to short courses of gonadotropins. The source of immature oocytes is an important feature for the subsequent embryonic development and pregnancy, as well healthy live births. IVM is an efficient treatment that has already achieved significant outcomes in terms of acceptable pregnancies and implantation rates and resulted in the births of several thousands of healthy babies. As the development of IVM treatment continues, an attractive possibility for improving the already successful outcome is to combine a natural cycle in vitro fertilization (IVF) treatment with an immature oocyte retrieval followed by IVM of those immature oocytes. If the treatment processes can be simplified with immature oocyte retrieval, different types of infertile women may be able to take advantage of these treatments. Although IVM treatment is still considered experimental by the society, it is time to reconsider the IVM technological evolution. Mild stimulation IVF combined with IVM treatment represents a viable alternative to the standard treatment, and as data accumulate over time, it may prove to be an optimal first-line treatment approach.
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