CELL PROLIFERATION
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2019
·Vol. 53
·期 2
·e12737
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IF 5.039
Xiao-Wei Gu,Yan Yang,Tao Li,Zi-Cong Chen,Tao Fu,Ji-Min Pan,Jian-Ping Ou,Zeng-Ming Yang
Objective Embryo implantation needs a reciprocal interaction between competent embryo and receptive endometrium. Adenosine triphosphate (ATP) produced by stressed or injured cells acts as an important signalling molecule. This study aims to investigate whether adenosine triphosphate (ATP) plays an important role in the dialogue of human blastocyst-endometrium. Materials and methods The concentration of lactate was analysed in culture medium from human embryos collected from in vitro fertilization patients. Extracellular ATP was measured by ATP Bioluminescent Assay Kit. Ishikawa cells and T-HESCs were treated with ATP, ATP receptor antagonist, ATP hydrolysis enzyme or inhibitors of ATP metabolic enzymes. The levels of gene expression were evaluated by real-time PCR and immunoassay. Results We showed that injured human endometrial epithelial cells could rapidly release ATP into the extracellular environment as an important signalling molecule. In addition, blastocyst-derived lactate induces the release of non-lytic ATP from human endometrial receptive epithelial cells via connexins. Extracellular ATP stimulates the secretion of IL8 from epithelial cells to promote the process of in vitro decidualization. Extracellular ATP could also directly promote the decidualization of human endometrial stromal cells via P2Y-purinoceptors. More importantly, the supernatants of injured epithelial cells clearly induce the decidualization of stromal cells in time-dependent manner. Conclusion Our results suggest that ATP should play an important role in human blastocyst-endometrium dialogue for the initiation of decidualization.
研究领域:
生殖生物学
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分子生物学
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细胞信号传导
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DOI
PubMed
高影响因子
Cells
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2024
·Vol. 13
·期 3
·206
·
IF 5.1
Meng-Yuan Li,Ying Wang,Ying Wu,Xu-Yu Zhao,Zhen-Shan Yang,Bo Li,Si-Ting Chen,Yu-Ying He,Zeng-Ming Yang
(1) Background: Inflammatory responses are implicated in embryo implantation, decidualization, pregnancy maintenance and labor. Both embryo implantation and decidualization are essential to successful pregnancy in rodents and primates. S100A6 is involved in inflammation, tumor development, apoptosis and calcium homeostasis. S100A6 is strongly expressed in mouse decidua, but the underlying mechanisms of how S100A6 regulates implantation and decidualization are poorly defined. (2) Methods: Mouse endometrial stromal and epithelial cells are isolated from day 4 pseudopregnant mouse uteri. Both immunofluorescence and Western blotting are used to analyze the expression and localization of proteins. The molecular mechanism is verified in vitro by Western blotting and the quantitative polymerase chain reaction. (3) Results: From days 4 to 8 of pregnancy, S100A6 is specifically expressed in mouse subluminal stromal cells. Blastocyst-derived lactic acid induces AA secretion by activating the luminal epithelial p-cPLA2. The epithelial AA induces stromal S100A6 expression through the COX2/PGI2/PPAR δ pathway. Progesterone regulates S100A6 expression through the progesterone receptor (PR). S100A6/RAGE signaling can regulate decidualization via EGFR/ERK1/2 in vitro. (4) Conclusions: S100A6, as an inflammatory mediator, is important for mouse implantation and decidualization.Keywords:decidualization;implantation;S100A6;RAGE;inflammation
研究领域:
生殖生物学
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分子生物学
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免疫学
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PubMed
高影响因子
GENES AND IMMUNITY
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2024
·
IF 5
Yue Wu,Huiling Zhou,Yuxin Liu,Ling Wang,Feng Gao,Qicai Liu
Repeated implantation failure (RIF) is one of the most prominent problems in the field of assisted reproduction. Neu5Gc on the surface of decidual macrophages (dMΦ) leads to different activation patterns of dMΦ, which affects embryo implantation and development. Cmah −/− (Neu5Gc-deficient) mice induced to produce anti-Neu5Gc antibodies in vivo were given a special diet rich in Neu5Gc and their fertility was monitored. The long-term diet rich in Neu5Gc induced the decrease of endometrial receptivity of female mice. The pregnancy rate of female mice fed the normal diet was 63.6% ( n = 11) and the average number of embryos was 9.571 ± 1.272, while the pregnancy rate of female mice fed the diet rich in Neu5Gc was 36.4% ( n = 11) and the average number of embryos in pregnant mice was 5.750 ± 3.304. The intake of Neu5Gc and the production of anti-Neu5Gc antibody led to M1 polarization of endometrial dMΦ and abnormal embryo implantation.
研究领域:
生殖生物学
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免疫学
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胚胎学
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PubMed
高影响因子
REPRODUCTIVE BIOMEDICINE ONLINE
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2020
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IF 3.218
Xiaoyan Wan,Xiaomei He,Qian Liu,Peng Duan,Honggang Li
Research question Frequent and mild scrotal heat stress (fmSHS) often occurs in humans. The aim of this study was to determine the impact of fmSHS on natural fertility , the IVF–embryo transfer (IVF–ET) process and the offspring sex ratio. Design Male mice were randomly divided into four groups: no scrotal heat stress (SHS) (controls) and those subjected to SHS at 37°C, 39°C or 41°C for 30 min once a week for 5 consecutive weeks. The testis, epididymis and sperm quality were assessed to evaluate the effects of different degrees of SHS, to establish an fmSHS model. Then, natural fertility, IVF–embryo transfer (IVF–ET) results, embryo development, offspring sex ratio and the X/Y chromosome-bearing sperm ratio were examined. Results SHS at 39°C and 41°C caused mild impairment to spermatozoa , leading to a phenotype similar to oligoasthenozoospermia in humans. Given that most SHS conditions in humans are close to body temperature, SHS of 39°C was adopted to build the fmSHS model. fmSHS reduced the fertilization rate, impaired on-time development and reduced the implantation rate of the embryos in the IVF–ET process, but it did not affect the development or function of blastocysts . The fmSHS mice produced more Y chromosome-bearing spermatozoa and propagated more male offspring. Conclusions fmSHS not only reduced the fertilization ability of spermatozoa but also influenced their function beyond fertilization, in addition to changing the offspring sex ratio. These results may help to shed new light on the infertility treatment of males with scrotal heat risk and the health concerns of offspring propagated from these fathers.
研究领域:
生殖生物学
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男科学
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胚胎学
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PubMed
高影响因子
Stem Cell Research & Therapy
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2022
·Vol. 13
·期 1
·1-19
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IF 8.079
Lin Yifeng,Dong Shunni,Ye Xiaohang,Liu Juan,Li Jiaqun,Zhang Yanye,Tu Mixue,Wang Siwen,Ying Yanyun,Chen Ruixue,Wang Feixia,Ni Feida,Chen Jianpeng,Du Binyang,Zhang Dan
Background Thin endometrium is a primary cause of defective endometrial receptivity, resulting in infertility or recurrent miscarriage. Much effort has been devoted toward regenerating thin endometrium by stem cell-based therapies. The human placenta-derived mesenchymal stem cells (HP-MSCs) are emerging alternative sources of MSCs with various advantages. To maximize their retention inside the uterus, we loaded HP-MSCs with cross-linked hyaluronic acid hydrogel (HA hydrogel) to investigate their therapeutic efficacy and possible underlying mechanisms.
Methods Ethanol was injected into the mice uterus to establish the endometrium-injured model. The retention time of HP-MSCs and HA hydrogel was detected by in vivo imaging, while the distribution of HP-MSCs was detected by immunofluorescence staining. Functional restoration of the uterus was assessed by testing embryo implantation rates. The endometrial morphological alteration was observed by H&E staining, Masson staining, and immunohistochemistry. In vitro studies were further conducted using EdU, transwell, tube formation, and western blot assays. Results Instilled HP-MSCs with HA hydrogel (HP-MSCs-HA) exhibited a prolonged retention time in mouse uteri than normal HP-MSCs. In vivo studies showed that the HP-MSCs-HA could significantly increase the gland number and endometrial thickness ( P < 0.001, P < 0.05), decrease fibrous area ( P < 0.0001), and promote the proliferation and angiogenesis of endometrial cells (as indicated by Ki67 and VEGF, P < 0.05, P < 0.05, respectively) in mice injured endometrium. HP-MSCs-HA could also significantly improve the embryo implantation rate ( P < 0.01) compared with the ethanol group. Further mechanistic study showed the paracrine effects of HP-MSCs. They could not only promote the proliferation and migration of human endometrial stromal cells via the JNK/Erk1/2-Stat3-VEGF pathway but also facilitate the proliferation of glandular cells via Jak2-Stat5 and c-Fos-VEGF pathway. In turn, the increased VEGF in the endometrium promoted the angiogenesis of endothelial cells. Conclusion Our study suggested the potential therapeutic effects and the underlying mechanisms of HP-MSCs-HA on treating thin endometrium. HA hydrogel could be a preferable delivery method for HP-MSCs, and the strategy represents a promising therapeutic approach against endometrial injury in clinical settings. Graphical abstract
研究领域:
生殖医学
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干细胞治疗
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组织工程
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再生医学
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DOI
PubMed
高影响因子
ACS Nano
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2023
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IF 17.1
Zhenning Su,Cancan Yao,Joanne Tipper,Lijun Yang,Xiangbo Xu,Xihua Chen,Guo Bao,Bin He,Xiaoxue Xu,Yufeng Zheng
Effective contraceptives have been comprehensively adopted by women to prevent the negative consequences of unintended pregnancy for women, families, and societies. With great contributions of traditional hormonal drugs and intrauterine devices (IUDs) to effective female contraception by inhibiting ovulation and deactivating sperm, their long-standing side effects on hormonal homeostasis and reproductive organs for females remain concerns. Herein, we proposed a nanostrategy for female contraceptives, inducing embryonic trophoblast cell death using nanoparticles to prevent embryo implantation. Cupric oxide nanoparticles (CuO NPs) were adopted in this work to verify the feasibility of the nanostrategy and its contraceptive efficacy. We carried out the in vitro assessment on the interaction of CuO NPs with trophoblast cells using the HTR8/SVneo cell line. The results showed that the CuO NPs were able to be preferably uptaken into cells and induced cell damage via a variety of pathways including oxidative stress, mitochondrial damage, DNA damage, and cell cycle arrest to induce cell death of apoptosis, ferroptosis, and cuproptosis. Moreover, the key regulatory processes and the key genes for cell damage and cell death caused by CuO NPs were revealed by RNA-Seq. We also conducted in vivo experiments using a rat model to examine the contraceptive efficacy of both the bare CuO NPs and the CuO/thermosensitive hydrogel nanocomposite. The results demonstrated that the CuO NPs were highly effective for contraception. There was no sign of disrupting the homeostasis of copper and hormone, or causing inflammation and organ damage in vivo. In all, this nanostrategy exhibited huge potential for contraceptive development with high biosafety, efficacy, clinical translation, nonhormonal style, and on-demand for women.
研究领域:
纳米技术
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生殖生物学
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避孕科学
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细胞生物学
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分子生物学
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PubMed
高影响因子
TALANTA
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2024
·
IF 5.6
Yijiao Qu,Ming Chen,Yiran Wang,Liangliang Qu,Ruiyue Wang,Huihui Liu,Liping Wang,Zongxiu Nie
Infertility presents a widespread challenge for many families worldwide, often arising from various gynecological diseases (GDs) that hinder successful pregnancies. Current diagnostic methods for GDs have disadvantages such as low efficiency, high cost, misdiagnose, invasive injury and etc. This paper introduces a rapid, non-invasive, efficient, and straightforward analytical method that utilizes desorption, separation, and ionization mass spectrometry (DSI-MS) platform in conjunction with machine learning (ML) to detect urine metabolite fingerprints in patients with different GDs. We analyzed 257 samples from patients diagnosed with polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), diminished ovarian reserve (DOR), endometriosis (EMS), recurrent pregnancy loss (RPL), recurrent implantation failure (RIF), and 87 samples from healthy control (HC) individuals. We identified metabolite differences and dysregulated pathways through dimensionality reduction methods, with the result of the discovery of 7 potential biomarkers for GDs diagnosis. The ML method effectively distinguished subtle differences in urine metabolite fingerprints. We anticipate that this innovative approach will offer a patient-friendly, rapid screening, and differentiation method for infertility-related GDs patients.
研究领域:
生殖医学
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质谱分析
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机器学习
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代谢组学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Sisi Zhang,Erna Jia,Weiqi Zhang,Zhiying Wang,Da Deng,Yixin Zhang,Xuefeng Huang,Qingquan Tian,Ying Tan,Bujun Wang,Feng Lin
The development of novel therapeutic approaches to facilitate endometrial repair and regeneration while preventing adhesion recurrence is a crucial research objective aimed at enhancing clinical outcomes for women with intrauterine adhesions (IUA). In this study, we introduced an injectable Alg-GMA/PTSB zwitterionic hydrogel, characterized by excellent biocompatibility, anti-protein adsorption properties, and biodegradability. In a rat model, the hydrogel significantly promoted the regeneration and angiogenesis of damaged endometrial tissue, leading to improved recovery of epithelial cells, glands, proliferation, and vascularization. Furthermore, it exhibited the ability to suppress cellular apoptosis and collagen deposition, thereby mitigating fibrosis. Additionally, the hydrogel restored the expression of estrogen/progesterone receptors and endometrial receptivity markers, contributing to enhanced embryo implantation and fertility. These findings underscore the potential of the hydrogel as a promising therapeutic strategy for addressing endometrial injury, reducing fibrosis, restoring fertility, and ultimately improving outcomes for women with IUA.
研究领域:
妇科学
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生殖医学
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生物材料
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组织工程
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DOI
PubMed
高影响因子
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