Avoiding wound infection and retaining an appropriate level of moisture around woundz are major challenges in wound care management. Therefore, designing hydrogels with desired antibacterial ...performance and good water‐maintaining ability is of particular significance to promote the development of wound dressing. Thus a series of hydrogels are prepared by crosslinking of Ag/graphene composites with acrylic acid and N,N′‐methylene bisacrylamide at different mass ratios. The antibacterial performance and accelerated wound‐healing ability of hydrogel are systematically evaluated with the aim of attaining a novel and effective wound dressing. The as‐prepared hydrogel with the optimal Ag to graphene mass ratio of 5:1 (Ag5G1) exhibits stronger antibacterial abilities than other hydrogels. Meanwhile, Ag5G1 hydrogel exhibits excellent biocompatibility, high swelling ratio, and good extensibility. More importantly, in vivo experiments indicate that Ag5G1 hydrogel can significantly accelerate the healing rate of artificial wounds in rats, and histological examination reveals that it helps to successfully reconstruct intact and thickened epidermis during 15 day of healing of impaired wounds. In one word, the present approach can shed new light on designing of antibacterial material like Ag/graphene composite hydrogel with promising applications in wound dressing.
A novel application range of graphene hydrogel in wound dressing is exploited. The hydrogels are composed of Ag–graphene composite, AA, and BIS. When the mass ratio of Ag to graphene is 5:1, the hydrogel (Ag5G1) shows strong antibacterial activity, large swelling ratio, excellent biocompatibility, and good extensibility, and it can significantly accelerate the healing rate of artificial wounds in rats.
In a multicenter, randomized trial, live-birth rates did not differ significantly according to fresh- or frozen-embryo transfer among ovulatory women with infertility. Frozen-embryo transfer resulted ...in a lower risk of the ovarian hyperstimulation syndrome.
The aim of this study was to investigate the impact of a history of recurrent ectopic pregnancy (EP) on pregnancy outcomes of subsequent in vitro fertilization (IVF) treatment. A retrospective cohort ...study involving 457 women with a history of recurrent EP (REP group), 912 women with a history of single EP (SEP group), and 1169 women with a history of intrauterine pregnancy (IUP group) as the control group, was conducted. IVF outcomes were compared for each cohort. The incidence of EP in the REP group after IVF treatment was significantly lower than those in the SEP group (2.4% vs. 6.8%, P = 0.011), and similar to those in the IUP group (2.4% vs. 2.1%, P = 0.830). No significant differences were observed in the clinical pregnancy rate, miscarriage rate, and live birth rate among the three groups. There was no statistically significant difference in the recurrent EP rate between the salpingectomy and salpingostomy treatments. Adjusting for maternal and treatment factors did not influence live birth rates for women with previous REP compared with women with previous SEP and those with IUP. The odds of EP were 82.2% lower (OR 0.178, 95% CI 0.042-0.762; P = 0.020) in women who had blastocyst transfer compared with cleavage embryo transfer in the SEP group. The odds of EP were over six times (OR 6.260, 95% CI 1.255-31.220; P = 0.025) in women who underwent double embryo transfer as opposed to single embryo transfer in the IUP group. Our results indicate that women with previous recurrent EP have a lower risk of EP after IVF in comparison with women with previous single EP. Previous EP has no significant adverse effect on the main IVF outcomes. The salpingostomy and salpingectomy treatments of EP do not significantly affect the incidence of recurrent EP after IVF.
ObjectivesThe aim of this study was to investigate the impact of a history of recurrent ectopic pregnancy (EP) on pregnancy outcomes of subsequent in vitro fertilization (IVF) treatment.MethodsA ...retrospective cohort study involving 457 women with a history of recurrent EP (REP group), 912 women with a history of single EP (SEP group), and 1169 women with a history of intrauterine pregnancy (IUP group) as the control group, was conducted. IVF outcomes were compared for each cohort.ResultsThe incidence of EP in the REP group after IVF treatment was significantly lower than those in the SEP group (2.4% vs. 6.8%, P = 0.011), and similar to those in the IUP group (2.4% vs. 2.1%, P = 0.830). No significant differences were observed in the clinical pregnancy rate, miscarriage rate, and live birth rate among the three groups. There was no statistically significant difference in the recurrent EP rate between the salpingectomy and salpingostomy treatments. Adjusting for maternal and treatment factors did not influence live birth rates for women with previous REP compared with women with previous SEP and those with IUP. The odds of EP were 82.2% lower (OR 0.178, 95% CI 0.042-0.762; P = 0.020) in women who had blastocyst transfer compared with cleavage embryo transfer in the SEP group. The odds of EP were over six times (OR 6.260, 95% CI 1.255-31.220; P = 0.025) in women who underwent double embryo transfer as opposed to single embryo transfer in the IUP group.ConclusionOur results indicate that women with previous recurrent EP have a lower risk of EP after IVF in comparison with women with previous single EP. Previous EP has no significant adverse effect on the main IVF outcomes. The salpingostomy and salpingectomy treatments of EP do not significantly affect the incidence of recurrent EP after IVF.
Abstract
STUDY QUESTION
Does metformin inhibit excessive androgen-induced endoplasmic reticulum (ER) stress in mouse granulosa cells (GCs) in vivo and in vitro?
SUMMARY ANSWER
Metformin inhibits ...testosterone-induced ER stress and unfolded protein response (UPR) activation by suppressing p38 MAPK phosphorylation in ovarian GCs.
WHAT IS KNOWN ALREADY
Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism. Excessive testosterone induces ER stress and UPR activation in human cumulus cells, leading to cell apoptosis. Metformin has potential inhibitory effects on ER stress and UPR activation, as demonstrated in human pancreatic beta cells and obese mice.
STUDY DESIGN, SIZE, DURATION
Cumulus cells and follicular fluid were collected from 25 women with PCOS and 25 controls at our IVF centre. A dihydrotestosterone (DHT)-induced PCOS mouse model was constructed and treated with or without metformin. Primary mouse GCs and cumulus-oocyte complexes (COCs) were cultured with testosterone, metformin, a p38 MAPK inhibitor, or p38 MAPK small interfering RNA.
PARTICIPANTS/MATERIALS, SETTING, METHODS
The levels of UPR sensor proteins and UPR-related genes were measured in cumulus cells from PCOS and control patients by real-time quantitative PCR (qPCR) and western blot. The ovaries, oocytes, GCs and COCs were collected from PCOS mice treated with metformin and controls. The expressions of ER stress markers and p38 MAPK phosphorylation were assessed by qPCR, western blot and immunofluorescence. A subsequent in vitro analysis with primary cultured GCs and COCs was used to confirm the influence of metformin on ER stress activation by qPCR and western blot. Finally, the effects of ER stress activation on GCs and COCs in relation to LH responsiveness were examined by qPCR and COC expansion.
MAIN RESULTS AND THE ROLE OF CHANCE
The expression of the ER stress markers GRP78, CHOP and XBP1s in the cumulus cells was higher in PCOS patients than in control patients, as were the levels of the UPR sensor proteins p-IRE1α, p-EIF2α and GRP78. Compared to those of control mice, the ovaries, GCs and COCs of DHT-treated PCOS mice showed increased levels of ER stress marker genes and proteins. Hyperandrogenism in PCOS mouse ovaries also induced p38 MAPK phosphorylation in COCs and GCs. Metformin inhibited ER stress activation was associated with decreased p-p38 MAPK levels. In vitro experiments, testosterone-induced ER stress was mitigated by metformin or p38 MAPK inhibition in primary cultured GCs and COCs. COCs expanded rapidly in the presence of testosterone during LH administration, and ovulation-related genes, namely, Areg, Ereg, Ptgs2, Sult1e1, Ptx3 and Tnfaip6, were strongly expressed in the COCs and GCs. These effects were reversed by treatment with metformin, an ER stress inhibitor or by knockdown of p38 MAPK.
LIMITATIONS, REASONS FOR CAUTION
The number of PCOS patients in this study was small.
WIDER IMPLICATIONS OF THE FINDINGS
This study provides further evidence for metformin as a PCOS treatment.
STUDY FUNDING/COMPETING INTEREST(S)
This study was funded by the National Key Research and Developmental Program of China (2018YFC1004800), the Key Research and Development Program of Zhejiang Province (2017C03022), the Zhejiang Province Medical Science and Technology Plan Project (2017KY085, 2018KY457), the National Natural Science Foundation of China (31701260, 81401264, 81701514), and the Special Funds for Clinical Medical Research of the Chinese Medical Association (16020320648). The authors report no conflict of interest in this work and have nothing to disclose.
TRIAL REGISTRATION NUMBER
N/A.
Due to the physiological alteration during pregnancy, maternal gut microbiota changes following the metabolic processes. Recent studies have revealed that maternal gut microbiota is closely ...associated with the immune microenvironment in utero during pregnancy and plays a vital role in specific pregnancy complications, including preeclampsia, gestational diabetes, preterm birth and recurrent miscarriages. Some other evidence has also shown that aberrant maternal gut microbiota increases the risk of various diseases in the offspring, such as allergic and neurodevelopmental disorders, through the immune alignment between mother and fetus and the possible intrauterine microbiota. Probiotics and the high-fiber diet are effective inventions to prevent mothers and fetuses from diseases. In this review, we summarize the role of maternal gut microbiota in the development of pregnancy complications and the health condition of future generations from the perspective of immunology, which may provide new therapeutic strategies for the health management of mothers and offspring.
Abstract
To evaluate the association between the number of oocytes retrieved and cumulative live birth rate (CLBR) in different female age strata. 17,931 women undergoing their first IVF/ICSI-ET ...cycle in the Sir Run Run Shaw Hospital of Zhejiang University were grouped by age (A: ≤ 35 years; B: ≥ 36 years) as well as the number of oocytes retrieved (a: ≤ 5; b:6–9; c:10–14; d: ≥ 15). Multivariate regression analysis was performed to assess the OR of CLBR for the variable ‘age’ and ‘number of oocytes retrieved’. The group ≥ 36 years exhibited lower cumulative pregnancy rates (CPRs) and cumulative live birth rates (CLBRs), which are proportional to the number of oocytes retrieved but opposite to increasing age. Multivariate logistic regression analysis revealed that the age and number of oocytes retrieved remain significant independent predictive factors (P < 0.001). Age and number of oocytes retrieved are two independent factors affecting the CLBR. The discrepancy of the minimum number of oocytes retrieved for patients with different ages to achieve ideal CLBR is instructive for clinical practice. The practice of controlling the stimulation dose is feasible for patients ≤ 35 years who can achieve over 60% CLBR once the number of oocytes obtained is more than 6. However, additional stimulation cycles and accumulation of embryos are necessary for elderly group especially those ≥ 38 years old who need more than 14 oocytes to obtain higher live birth rate.
We aimed to investigate the difference in the time to pregnancy (TTP) between women with previous ectopic pregnancy (EP) and control women following in vitro fertilization (IVF) treatment and the ...association between TTP and the number of oocytes retrieved and embryos available. A retrospective study involving 1097 women, 547 of which had previous EP and 550 were control women whose previous pregnancy were abortion, was conducted. Women in the EP group had significantly longer median TTP than those in the control group (36; range, 12-252 vs 28; range, 12-220; P = 0.019). For women with previous EP, > 48 months TTP was most likely associated with low numbers of oocytes retrieved and embryos available compared to TTP of ≤ 24 months or 25-48 months, and women with younger age had a shorter TTP, higher numbers of oocytes retrieved and embryos available. A Cox proportional hazards model showed that maternal age was significantly related to the pregnancy over the TTP (adjusted hazard ratio, 0.934; P < 0.001). In conclusion, women with previous EP have a significantly increased TTP than control women with previous abortion. For women with previous EP, TTP is negatively associated with the numbers of oocytes retrieved and embryos available.
Stem cell-based and stem cell-derived exosome-based therapies have shown promising potential for endometrial regeneration and the clinical treatment of intrauterine adhesions (IUAs). Evidence shows ...that apoptosis occurs in a majority of grafted stem cells, and apoptotic bodies (ABs) play a critical role in compensatory tissue regeneration. However, the therapeutic potential of AB-based therapy and its mechanism have not been explored in detail. Here, a cell-free therapeutic strategy was developed by incorporating mesenchymal stem cell-derived ABs into a hyaluronic acid (HA) hydrogel to achieve endometrial regeneration and fertility restoration. Specifically, we found that the ABs could induce macrophage immunomodulation, cell proliferation, and angiogenesis in vitro. The HA hydrogel promoted the retention of ABs and facilitated their continuous release. In a murine model of acute endometrial damage and a rat model of IUAs, in situ injection of the AB-laden HA hydrogel could efficiently reduce fibrosis and promote endometrial regeneration, resulting in the fertility restoration. Consequently, ABs show good potential as therapeutic vesicles, and the AB-laden HA hydrogel appears to be a clinically feasible and cell-free alternative for endometrial regeneration and IUA treatment.
An apoptotic body (AB)-laden hyaluronic acid (HA) hydrogel was designed to deliver ABs in situ to treat intrauterine adhesions (IUAs) in a rodent model. It was demonstrated that after treatment with the AB-laden HA hydrogel, endometrial regeneration and fertility restoration could be achieved owing to the positive effects of ABs on macrophage immunomodulation, cell proliferation, and angiogenesis. Display omitted
●Human umbilical cord derived apoptotic bodies induce macrophage immunomodulation, cell proliferation and angiogenesis●A strategy of apoptotic bodies associated with hyaluronic acid hydrogel promotes apoptotic bodies retention and continuous release●The implantation of the apoptotic body-laden hyaluronic acid hydrogel into uterine cavity effectively promoted endometrial regeneration and fertility restoration in a rodent model of intrauterine adhesion
Endometriosis an important cause of female infertility and seriously impact physical and psychological health of patients. Endometriosis is now considered to be a public health problem that deserves ...in-depth investigation, especially the etiopathogenesis of endometriosis-associated infertility. We aimed to illuminate the etiopathogenesis of endometriosis-associated infertility that involve excessive oxidative stress (OS) induced pathological changes of ovary cumulus granulosa cell (GCs). Senescence-associated β-galactosidase (SA β-gal) activity in GCs from endometriosis patients, soluble isoform of advanced glycation end products receptor (sRAGE) expression in follicular fluid from endometriosis patients and differentially expressed senescence-associated secretory phenotype factors (IL-1β, MMP-9, KGF and FGF basic protein) are all useful indexes to evaluate oocyte retrieval number and mature oocyte number. RNA-sequencing and bioinformatics analysis indicated senescent phenotype of endometriosis GCs and aggravated endoplasmic reticulum (ER) stress in endometriosis GCs. Targeting ER stress significantly alleviated OS-induced GCs senescence as well as mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) reduction in GCs. Moreover, melatonin administration rescued OS-enhanced ER stress, cellular senescence, and MMP and ATP abnormities of endometriosis GCs in vitro and in vivo. In conclusion, our results indicated excessive reactive oxygen species induces senescence of endometriosis GCs via arouse ER stress, which finally contributes to endometriosis-associated infertility, and melatonin may represent a novel adjuvant therapy strategy for endometriosis-associated infertility.
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•Endometriosis patients ovary cumulus granulosa cells (GCs) show senescence phenotype.•Excessive oxidative stress in GCs drives cellular senescence via activating ER stress.•Melatonin alleviates ER stress and GCs senescence in vitro and in vivo.
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