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Adipose progenitor cells (APCs) are heterogeneous stromal cells and help to maintain metabolic homeostasis. However, the influence of obesity on human APC heterogeneity and the role of APC subpopulations on regulating glucose homeostasis remain unknown. Here, we find that APCs in human visceral adipose tissue contain four subsets. The composition and functionality of APCs are altered in patients with type 2 diabetes (T2D). CD9+CD55low APCs are the subset which is significantly increased in T2D patients. Transplantation of these cells from T2D patients into adipose tissue causes glycemic disturbance. Mechanistically, CD9+CD55low APCs promote T2D development through producing bioactive proteins to form a detrimental niche, leading to upregulation of adipocyte lipolysis. Depletion of pathogenic APCs by inducing intracellular diphtheria toxin A expression or using a hunter-killer peptide improves obesity-related glycemic disturbance. Collectively, our data provide deeper insights in human APC functionality and highlights APCs as a potential therapeutic target to combat T2D. All mice utilized in this study are male. Adipose tissue harbors functionally distinct progenitor cell subsets. Using scRNAseq and functional assays, we disclose a pathogenic adipose progenitor subset, which impairs glycose homeostasis through the construction of a detrimental niche. [ABSTRACT FROM AUTHOR]

Intrauterine adhesion is a major cause of female reproductive disorders. Although we and others uncontrolled pilot studies showed that treatment with autologous bone marrow stem cells made a few patients with severe intrauterine adhesion obtain live birth, no large sample randomized controlled studies on this therapeutic strategy in such patients have been reported so far. To verify if the therapy of autologous bone marrow stem cells-scaffold is superior to traditional treatment in moderate to severe intrauterine adhesion patients in increasing their ongoing pregnancy rate, we conducted this randomized controlled clinical trial. Totally 195 participants with moderate to severe intrauterine adhesion were screened and 152 of them were randomly assigned in a 1:1 ratio to either group with autologous bone marrow stem cells-scaffold plus Foley balloon catheter or group with only Foley balloon catheter (control group) from February 2016 to January 2020. The per-protocol analysis included 140 participants: 72 in bone marrow stem cells-scaffold group and 68 in control group. The ongoing pregnancy occurred in 45/72 (62.5%) participants in the bone marrow stem cells-scaffold group which was significantly higher than that in the control group (28/68, 41.2%) (RR=1.52, 95%CI 1.08–2.12, P=0.012). The situation was similar in live birth rate (bone marrow stem cells-scaffold group 56.9% (41/72) vs. control group 38.2% (26/68), RR=1.49, 95%CI 1.04–2.14, P=0.027). Compared with control group, participants in bone marrow stem cells-scaffold group showed more menstrual blood volume in the 3rd and 6th cycles and maximal endometrial thickness in the 6th cycle after hysteroscopic adhesiolysis. The incidence of mild placenta accrete was increased in bone marrow stem cells-scaffold group and no severe adverse effects were observed. In conclusion, transplantation of bone marrow stem cells-scaffold into uterine cavities of the participants with moderate to severe intrauterine adhesion increased their ongoing pregnancy and live birth rates, and this therapy was relatively safe. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to identify the mechanism of Inhibin Subunit Beta B (INHBB), a member of the transforming growth factor-β (TGF-β) family involved in the regulation of human endometrial stromal cells (HESCs) decidualization in recurrent implantation failure (RIF). Methods: RNA-seq was conducted to identify the differentially expressed genes in the endometria from control and RIF patients. RT-qPCR, WB, and immunohistochemistry were performed to analyse the expression levels of INHBB in endometrium and decidualised HESCs. RT-qPCR and immunofluorescence were used to detect changes in the decidual marker genes and cytoskeleton after knockdown INHBB. Then, RNA-seq was used to dig out the mechanism of INHBB regulating decidualization. The cAMP analogue (forskolin) and si-INHBB were used to investigate the involvement of INHBB in the cAMP signalling pathway. The correlation of INHBB and ADCY expression was analysed by Pearson's correlation analysis. Results: Our results showed significantly reduced expression of INHBB in endometrial stromal cells of women with RIF. In addition, INHBB was increased in the endometrium of the secretory phase and significantly induced in in-vitro decidualization of HESCs. Notably, with RNA-seq and siRNA-mediated knockdown approaches, we demonstrated that the INHBB-ADCY1-mediated cAMP signalling pathway regulates the reduction of decidualization. We found a positive association between the expression of INHBB and ADCY1 in endometria with RIF (R2 = 0.3785, P = 0.0005). Conclusions: The decline of INHBB in HESCs suppressed ADCY1-induced cAMP production and cAMP-mediated signalling, which attenuated decidualization in RIF patients, indicating that INHBB is an essential component in the decidualization process. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between visceral adipocyte hypertrophy and the onset and development of non-alcoholic fatty liver disease (NAFLD) in subjects with different degrees of adiposity. Methods: Omental adipose tissue and liver biopsies were collected from obese subjects. NAFLD was defined according to the NASH Clinical Research Network scoring system. Adipocyte size was measured using pathological section analysis. Adipose tissue insulin resistance (Adipo-IR) was calculated as fasting insulin (pmol/L) × fasting free fatty acid concentration (mmol/L). Results: In total, 275 obese patients were enrolled, including 158 females and 58 males with NAFLD. In females, adipocyte size was significantly larger in NAFLD participants as compared to the controls (99.37 ± 14.18 vs. 84.14 ± 12.65 μ m, p < 0.001). Moreover, adipocyte size was larger in females with non-alcoholic steatohepatitis (NASH) as compared to those with non-alcoholic fatty liver (NAFL) (101.45 ± 12.77 vs. 95.79 ± 15.80 μ m, p = 0.015). Mediation analysis showed that adipocyte size impacted the NAFLD activity score through Adipo-IR (b = 0.007 [95% bootstrap CI 0.002, 0.013]). Furthermore, the females were divided into: Q1 (BMI < 32.5 kg/m2), Q2 (BMI 32.5–35.5 kg/m2), Q3 (BMI 35.5–38.8 kg/m2) and Q4 (BMI ≥ 38.8 kg/m2) according to BMI quartiles. Omental adipocyte size was larger in NAFLD subjects in Q1–Q3, but not in Q4. No similar results were observed in males. Conclusion: For the first time, we reported that visceral adipocyte hypertrophy was associated with the onset and progression of NAFLD in mild to moderate adiposity but not in severe obesity, which may be mediated by adipose tissue insulin resistance. [ABSTRACT FROM AUTHOR]

Background and aim: Body composition was associated with nonalcoholic steatohepatitis (NASH), but results were controversial probably due to gender differences. Hence, we aim to explore the association of body composition and NASH in males and females. Methods: We conducted a cross-sectional analysis of obese subjects undergone liver biopsy. According to NASH Clinical Research Network system, subjects were categorized as Normal Control (NC), non-NASH or NASH. Body composition was accessed by dual‐energy X‐ray absorptiometry. Results: This study enrolled 336 subjects (mean age 32.0 years, mean BMI 39.15 kg/m2, female, 64.0%). Males have lower relative muscle mass (RMM 55.21 ± 4.07%) and females have higher android to gynoid ratio (AGR, 0.82 ± 0.21) in NASH when compared with non-NASH (RMM 57.49 ± 4.75%; AGR 0.7 ± 0.15) and NC (RMM 58.69 ± 4.09%; AGR 0.66 ± 0.19, p < 0.05 for each). After adjusting for confounding factors, low RMM was the independent risk factor for NASH in males (odds ratio [OR] 0.550; 95% confidence interval [CI] 0.312–0.970), high AGR was the independent risk factor for NASH in females (OR 1.694; 95% CI 1.073–2.674). Further, RMM in males and AGR in females, respectively, was associated with liver steatosis and activity, but not with fibrosis. ROC curve revealed that the optimal cutoff value of RMM was 58.09% in males and AGR was 0.92 in females for predicting NASH. Conclusions: We firstly revealed that low RMM and high AGR were the independent risk factors for NASH in males and females, respectively, indicating that sex-specific interventions for improving body composition may reduce the risk of NASH in obese subjects. [ABSTRACT FROM AUTHOR]

Background: Although exogenous follicle-stimulating hormone (FSH) has been used for decades and millions of cycles have been performed worldwide until now, criteria for selecting the proper FSH starting dose have not been clearly identified. The aim of this study was to elaborate a formula based on markers of ovarian reserve for the calculation of the appropriate starting dose of FSH.Methods: A total of 931 patients underwent in vitro fertilization (IVF) treatment using long GnRH agonist protocol was retrospectively identified and reviewed. 673 cases of them with a normal ovarian response (4-14 retrieved oocytes) were used to analysis the predictive formula. All follicles 4-7 mm in diameter were counted in the same day of blood sample in both ovaries using transvaginal ultrasound scan. The modified protocol of each patient was recorded and analyzed in the same center. In another center were the numbers of retrieved oocytes of 750 validated patients recorded and analyzed.Results: A formula model based on age, AMH, and antral follicle count (AFC) was able to accurately predict the ovarian sensitivity and accounted for 57.2% of the variability of ovarian response to FSH. When tested in the same total population used to elaborate the model it predicts a high 46.88% rate of step-down protocol in higher-starting FSH dose group and about 57.92% of patients had their dose step-up modified in lower-starting FSH dose group during their treatment, respectively. And when tested in different population from another center used to elaborate the model it predicts a high 64.40% rate of ≥ 15 retrieved oocytes in higher-starting FSH dose group and about 22.50% of patients had ≤ 7 retrieved oocytes in lower-starting FSH dose group during their treatment, respectively.Conclusions: In the present study we demonstrated that the individualized FSH starting dose may be calculated on the basis of a woman's age, AMH and AFC. The formula model might be a useful, immediate, and easily applicable tool for clinicians to predict the tailored starting dose of FSH during their daily clinical practice. [ABSTRACT FROM AUTHOR]

Premature ovarian failure (POF) is a refractory disease; one of the most important goals of treatment is to improve fertility. In the study, collagen scaffold loaded with human umbilical cord–derived mesenchymal stem cells (collagen/UC-MSCs) transplantation in POF mice preserved ovarian function, as supported by increased estrogen (E2) and anti-Mullerian hormone (AMH) levels, increased ovarian volume, and an increased number of antral follicles. Immunohistochemistry results of Ki67 indicated transplantation of collagen/UC-MSCs promoted granulosa cell proliferation, which is crucial to oocyte maturation and follicular development. Additionally, transplantation of collagen/UC-MSCs significantly promoted ovarian angiogenesis with the increased expression of CD31. In general, collagen/UC-MSCs transplantation probably is an effective therapeutic strategy of POF. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of culture duration (embryo (day 3) transfer vs. blastocyst (day 5-6) transfer) on the birthweight of singletons from frozen embryo transfer (FET) cycles.Methods: A total of 1092 singletons were analyzed in this retrospective study. The distribution of large for gestational age (LGA) infants, the mean birthweight, and z scores of singletons were compared between the day 3 and day 5-6 transfer groups. Multiple linear regression analysis was performed to evaluate the relationships between confounding factors and singleton birthweight.Results: The proportion of LGA infants significantly increased with BMI (BMI < 20, 12.8%; 20 ≤ BMI ≤ 25, 23.2%; BMI > 25, 32.3%; P < 0.0001). However, the proportions of small for gestational age (SGA) and LGA infants were not significantly different between day 3 and day 5-6 transfers. The absolute mean birthweight of singletons was not significantly different between day 3 transfer (3422 ± 547 g) and day 5-6 transfer (3433 ± 559 g; P = 0.732). The z scores (calculated from a reference population) of singletons were also not significantly different between the two groups (0.499 vs. 0.533, P = 0.625). Multiple linear regression analysis showed that maternal BMI, gestational age, and infant gender had significant effects on singleton birthweight, while culture duration (P = 0.731) did not significantly affect singleton birthweight.Conclusions: In vitro culture duration did not affect the birthweight of newborns resulting from day 3 to day 5-6 transfers in FET cycles. [ABSTRACT FROM AUTHOR]

Purpose: To study the association between the numbers of oocytes retrieved and the cumulative live birth rates (LBR) in women aged 35-40 years undergoing long GnRH agonist IVF/ICSI cycles.Methods: A total of 931 women aged 35-40 years who underwent their first cycle of IVF/ICSI treatment between January 2010 and December 2013 at Nanjing Drum Tower Hospital were identified and reviewed. The main endpoint of this study was the cumulative LBR after one complete oocyte retrieval, which included fresh and all subsequent frozen-thaw embryo transfer cycles. Odds ratios (OR) and 95% confidence interval (CI) for live birth were estimated by multivariate logistic regression analysis. Furthermore, all the women were divided into four groups based on the number of oocytes retrieved: 0-4, 5-9, 10-14 or ≥15 oocytes group. Variables were then compared among groups.Results: We found that 634 out of the 931 patients (68.1%) achieved at least one live birth. The number of oocytes retrieved was an independent predictive factor for live birth, with OR 1.20 (95% CI 1.15-1.26) when adjusted for age (years), duration of infertility and Gn (gonadotrophin) doses. The cumulative LBR in the four different oocyte groups was 35.6, 68.8, 83.4 and 89.2%, respectively. When the 1-4 oocytes group was issued as a reference, the ORs for cumulative LBR gradually increased to 3.66, 6.74 and 11.77 in other three oocytes groups, respectively. The moderate-severe ovarian hyperstimulation syndrome (OHSS) rate was dramatically increased in the ≥15 oocytes group (6.9%) when compared to that in the 10-14 oocytes group (0.8%), while the cumulative LBR only increased 5.8% (from 83.4 to 89.2%).Conclusions: The ideal number of oocytes retrieved in women aged 35-40 years is 10-14 oocytes, which achieves a high cumulative LBR while maintaining an acceptable low OHSS rate. [ABSTRACT FROM AUTHOR]

Asherman's syndrome (AS) is a common disease that presents endometrial regeneration disorder. However, little is known about its molecular features of this aregenerative endometrium in AS and how to reconstruct the functioning endometrium for the patients with AS. Here, we report that ΔNp63 is significantly upregulated in residual epithelial cells of the impaired endometrium in AS; the upregulated-ΔNp63 induces endometrial quiescence and alteration of stemness. Importantly, we demonstrate that engrafting high density of autologous bone marrow mononuclear cells (BMNCs) loaded in collagen scaffold onto the uterine lining of patients with AS downregulates ΔNp63 expression, reverses ΔNp63-induced pathological changes, normalizes the stemness alterations and restores endometrial regeneration. Finally, five patients achieved successful pregnancies and live births. Therefore, we conclude that ΔNp63 is a crucial therapeutic target for AS. This novel treatment significantly improves the outcome for the patients with severe AS. [ABSTRACT FROM AUTHOR]

Introduction: Excessive inflammation results in adverse pregnancy outcomes, including embryonic resorption, fetal growth restriction, and preeclampsia. This study investigated whether curcumin, a highly safe anti-inflammation drug, had protective effect on lipopolysaccharide (LPS)-treated pregnant mice. Method: A mouse model of LPS-induced adverse pregnancy outcomes was generated by daily administering LPS from GD 13.5 to GD 16.5. Curcumin was given from GD 0.5. The effects of curcumin on maternal hypertension, proteinuria, pregnancy outcomes, as well as proinflammatory factors, chemokines, Akt, JNK, and P38 levels in placenta were examined. Results: Systolic blood pressure (156.6 ± 5.056 versus 125.5 ± 3.617 mmHg; P < 0.05) and proteinuria (22.36 ± 2.22 versus 12.70 ± 1.04 mg/L; P < 0.05) were decreased in the LPS+curcumin-treated group, as compared with the LPS-treated group. Curcumin also increased the number of live pups, fetal weight, and placental weight, while it decreased fetal resorption rate. Moreover, increased placental TNF-α, IL-1β, and IL-6 expressions in LPS-treated group were significantly suppressed after curcumin administration. Furthermore, decreased p-Akt level in placenta induced by LPS was improved by curcumin. Of note, the expression of p-Akt increased by curcumin was accompanied by the decreased chemokines MCP-1 and MIP-1 levels and fewer CD68-positive macrophages in the placenta. Conclusion: Curcumin inhibited the expression of proinflammatory factors and macrophage infiltration in placenta and ameliorated LPS-induced adverse pregnancy outcomes in mice by inhibiting inflammation via upregulation of phosphorylated Akt. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the usefulness of preimplantation genetic diagnosis (PGD) for the patient affected by congenital contractural arachnodactyly (CCA) and spinal and bulbar muscular atrophy (SBMA). Methods: Multiple displacement amplification (MDA) was performed for whole genome amplification (WGA) of biopsied trophectoderm (TE) cells. Direct mutation detection by sequencing and next-generation sequencing (NGS)-based single nucleotide polymorphism (SNP) haplotyping were used for CCA diagnosis. Direct sequencing of the PCR products and sex determination by amplification of sex-determining region Y (SRY) gene were used for SBMA diagnosis. After PGD, the unaffected blastocyst (B4) was transferred in the following frozen embryo transfer (FET). Results: In this PGD cycle, sixteen MII oocytes were inseminated by ICSI with testicular spermatozoa. Four blastocysts (B4, B5, B10, B13) were utilized for TE cell biopsy on day 5 after ICSI. After PGD, B4 was unaffected by CCA and SBMA. B5 was affected by CCA and carried SBMA. B10 was unaffected by CCA and carried SBMA. B13 was affected by CCA and unaffected by SBMA. B4 was the only unaffected blastocyst and transferred into the uterus for the subsequent FET cycle. The accuracy of PGD was confirmed by amniocentesis at 21 weeks of gestation. A healthy boy weighing 2850 g was born by cesarean section at the 38th week of gestation. Conclusions: PGD is a valid screening tool for patienst affected of CCA and SBMA to prevent transmission of these genetic diseases from parents to children. [ABSTRACT FROM AUTHOR]

Pedicle screw (PS) implantation is an ideal treatment for severe multilevel vertebra instabilities. The accuracy of fixating PS is a key factor of spinal surgery. We developed a near-infrared spectroscopy device with a needlelike optical fiber probe to monitor optical parameters (reduced scattering coefficient) of vertebra models in real time. The fresh-frozen cadaver, cats and porcine vertebras were first studied in the experiments. Moreover, the reduced scattering coefficient (μ' s) along the different trajectories of PS insertion was obtained. In the fresh-frozen cadavera experiment, μ' s values could be used to distinguish the different compositions of the thoracic vertebra. In cat vertebra experiment, μ' s values of vertebrae bones, including cortical bone (15.30 ± 0.18 cm(-1)), cancellous bone (7.84 ± 1.11 cm(-1)) and spinal cord (19.46 ± 0.21 cm(-1)), were different in vivo. In the pig vertebrae experiment, there were obvious differences between the normal and abnormal PS puncture curves based on μ' s values. Thus, μ' s values measured by using the proposed device could be used as the pattern factor in spinal fusion surgery. Our studies demonstrate that near-infrared spectroscopy method may be potentially used for assisting the PS insertion. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the impact of early rescue ICSI on neonatal outcome. Methods: This retrospective study compared the neonatal outcome of early rescue ICSI and ICSI with ejaculated sperm, including 233 children who were conceived after early rescue ICSI and a control group of 906 children who were conceived after ICSI with ejaculated sperm, and all of the children had a gestational age of 20 weeks or more. The numbers of live and stillbirths, perinatal deaths, prematurity, birthweights and birth defects of the children were compared. Results: Children in the early rescue ICSI group showed no increased risk of stillbirths, perinatal death or birth defects. Those children also did not differ from those of the ICSI with ejaculated sperm group in gender rate, birthweight, gestational age or prematurity. Conclusions: Early rescue ICSI did not increase the adverse effect on the neonatal outcome when compared to that of ICSI with ejaculated sperm. [ABSTRACT FROM AUTHOR]

Genes of the key enzymes for phycocyanobilin (PCB) biosynthesis were cloned into E. coli and combinationally expressed to produce phycocyanobilin, with autologous heme as substrate. Culture conditions were optimized to achieve ~3 mg PCB/l. A protocol for the purification of recombinant phycocyanobilin was established using solvent extraction combined with chromatography, which resulted in a final yield of ~0.3 mg PCB/l with a purity >95 %. Recombinant phycocyanobilin could scavenge hydroxyl radicals with an EC of 0.1 μM. [ABSTRACT FROM AUTHOR]

Chemotherapy treatment in women can frequently cause damage to the ovaries, which may lead to primary ovarian insufficiency (POI). In this study, we assessed the preventative effects of hyaluronic acid (HA) in immunosuppressive drug-induced POI-like rat models and investigated the possible mechanisms. We found that HA, which was reduced in primary and immunosuppressant-induced POI patients, could protect the immunosuppressant-induced damage to granulosa cells (GCs) in vitro. Then we found that HA blocked the tripterygium glycosides (TG) induced POI-like presentations in rats, including delayed or irregular estrous cycles, reduced 17 beta-estradiol(E2) concentration, decreased number of follicles, destruction of follicle structure, and damage of reproductive ability. Furthermore, we investigated the mechanisms of HA prevention effects on POI, which was associated with promotion of GC proliferation and PGRMC1 expression. In conclusion, HA prevents chemotherapy-induced ovarian damage by promoting PGRMC1 in GCs. This study may provide a new strategy for prevention and treatment of POI. [ABSTRACT FROM AUTHOR]