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Effect of melatonin on developmental competence, mitochondrial distribution, and intensity of fresh and vitrified/thawed in vitro matured buffalo oocytes 褪黑激素对新鲜和玻璃化/解冻体外成熟水牛卵母细胞发育能力、线粒体分布和强度的影响
IF 4.4 2区 医学 Q1 Medicine Pub Date : 2024-04-05 DOI: 10.1186/s12958-024-01209-7
Omaima Mohamed Kandil, Samar Mahfouz Abd El Rahman, Rania S. Ali, Esraa Aly Ismail, Nehad M. Ibrahim
Background: In livestock breeding, oocyte cryopreservation is crucial for preserving and transferring superior genetic traits. This study was conducted to examine the additional effect of melatonin to maturation and vitrification media on the in vitro developmental capacity, mitochondrial distribution, and intensity of buffalo oocytes. The study involved obtaining ovaries from a slaughterhouse and conducting two phases. In the first phase, high-quality oocytes were incubated in a maturation medium with or without 10−9M melatonin for 22 h (at 38.5°C in 5% CO2). Matured oocytes were fertilized in vitro and cultured in SOF media for seven days. In the second phase, vitrified in vitro matured oocytes were stored in vitrified media (basic media (BM) containing a combination of cryoprotectants (20% Ethyl Glycol and 20% Dimethyl sulfoxide), with or without melatonin, and then stored in liquid nitrogen. Normal vitrified/thawed oocytes were fertilized in vitro and cultured as described. Finally, the matured oocytes from the fresh and vitrified/thawed groups, both with and without melatonin, were stained using DAPI and Mitotracker red to detect their viability (nuclear maturation), mitochondrial intensity, and distribution using a confocal microscope. The study found that adding 10−9M melatonin to the maturation media significantly increased maturation (85.47%), fertilization rate (84.21%)cleavage (89.58%), and transferable embryo (48.83%) rates compared to the group without melatonin (69.85%,79.88%, 75.55%, and 37.25% respectively). Besides that, the addition of melatonin to the vitrification media improved the recovery rate of normal oocytes (83.75%), as well as the cleavage (61.80%) and transferable embryo (27.00%) rates when compared to the vitrified TCM group (67.46%, 51.40%, and 17.00%, respectively). The diffuse mitochondrial distribution was higher in fresh with melatonin (TCM + Mel) (80%) and vitrified with melatonin (VS2 + Mel groups) (76.70%), Furthermore, within the same group, while the mitochondrial intensity was higher in the TCM + Mel group (1698.60) than other group. In conclusion, Melatonin supplementation improves the developmental competence and mitochondrial distribution in buffalo oocytes in both cases(in vitro maturation and vitrification).
背景:在家畜育种中,卵母细胞冷冻保存对保存和传递优良遗传性状至关重要。本研究旨在探讨褪黑激素对水牛卵母细胞体外发育能力、线粒体分布和强度的影响。研究涉及从屠宰场获取卵巢,并分两个阶段进行。在第一阶段,优质卵母细胞在含有或不含有 10-9M 褪黑激素的成熟培养基中培养 22 小时(38.5°C,5% CO2)。成熟的卵母细胞在体外受精,并在 SOF 培养基中培养 7 天。在第二阶段,玻璃化的体外成熟卵母细胞被储存在玻璃化培养基(含有冷冻保护剂组合(20% 乙二醇和 20% 二甲基亚砜)的基本培养基 (BM))中,加入或不加入褪黑素,然后储存在液氮中。正常玻璃化/解冻卵母细胞在体外受精并按所述方法培养。最后,用 DAPI 和 Mitotracker red 染色新鲜组和玻璃化/解冻组(含或不含褪黑激素)的成熟卵母细胞,使用共聚焦显微镜检测其存活率(核成熟)、线粒体强度和分布。研究发现,与不添加褪黑素的组别(分别为 69.85%、79.88%、75.55% 和 37.25%)相比,在成熟培养基中添加 10-9M 褪黑素可显著提高成熟率(85.47%)、受精率(84.21%)、裂解率(89.58%)和可移植胚胎率(48.83%)。此外,与玻璃化中药组(分别为 67.46%、51.40% 和 17.00%)相比,在玻璃化培养基中添加褪黑激素可提高正常卵母细胞的回收率(83.75%)、卵裂率(61.80%)和可移植胚胎率(27.00%)。此外,在同一组中,新鲜加褪黑素组(TCM + Mel)(80%)和玻璃化加褪黑素组(VS2 + Mel)(76.70%)的线粒体弥散分布较高,而TCM + Mel组的线粒体强度(1698.60)高于其他组。总之,在体外成熟和玻璃化两种情况下,补充褪黑素都能提高水牛卵母细胞的发育能力和线粒体分布。
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引用次数: 0
The adipokines progranulin and omentin – novel regulators of basic ovarian cell functions 脂肪素原和网膜素--卵巢细胞基本功能的新型调节因子
IF 4.4 2区 医学 Q1 Medicine Pub Date : 2024-04-04 DOI: 10.1186/s12958-024-01215-9
Alexander V Sirotkin, Zuzana Fabová, Barbora Loncová, Maria Bauerová, Abdel Halim Harrath
The present study aimed to examine the effects of progranulin and omentin on basic ovarian cell functions. For this purpose, we investigated the effects of the addition of progranulin and omentin (0, 0.1, 1, or 10 ng/ml) on the viability, proliferation, apoptosis and steroidogenesis of cultured rabbit ovarian granulosa cells. To determine the importance of the interrelationships between granulosa cells and theca cells, we compared the influence of progranulin and omentin on progesterone and estradiol release in cultured granulosa cells and ovarian fragments containing both granulosa cells and theca cells. Cell viability, proliferation, cytoplasmic apoptosis and release of progesterone and estradiol were measured by Cell Counting Kit-8 (CCK-8), BrdU incorporation, cell death detection, and ELISA. Both progranulin and omentin increased granulosa cell viability and proliferation and decreased apoptosis. Progranulin increased progesterone release by granulosa cells but reduced progesterone output by ovarian fragments. Progranulin decreased estradiol release by granulosa cells but increased it in ovarian fragments. Omentin reduced progesterone release in both models. Omentin reduced estradiol release by granulosa cells but promoted this release in ovarian fragments. The present observations are the first to demonstrate that progranulin and omentin can be direct regulators of basic ovarian cell functions. Furthermore, the differences in the effects of these adipokines on steroidogenesis via granulosa and ovarian fragments indicate that these peptides could target both granulosa and theca cells.
本研究旨在探讨原花青素和网织红蛋白对卵巢细胞基本功能的影响。为此,我们研究了添加原粒细胞素和网织红细胞素(0、0.1、1 或 10 ng/ml)对培养的兔卵巢颗粒细胞的活力、增殖、凋亡和类固醇生成的影响。为了确定颗粒细胞和theca细胞之间相互关系的重要性,我们比较了progranulin和奥曲肽对培养的颗粒细胞和含有颗粒细胞和theca细胞的卵巢碎片中孕酮和雌二醇释放的影响。通过细胞计数试剂盒-8(CCK-8)、BrdU掺入、细胞死亡检测和酶联免疫吸附法测定了细胞活力、增殖、细胞质凋亡以及孕酮和雌二醇的释放。前胡素和网织红素都能提高颗粒细胞的活力和增殖,减少细胞凋亡。前列腺素能增加颗粒细胞释放孕酮,但减少了卵巢片段的孕酮输出。颗粒细胞释放的雌二醇减少,但卵巢片段释放的雌二醇增加。网织红霉素减少了两种模型中孕酮的释放。网织红蛋白减少了颗粒细胞的雌二醇释放,但促进了卵巢片段的雌二醇释放。目前的观察结果首次证明,原花青素和网织红素可直接调节卵巢细胞的基本功能。此外,这些脂肪因子通过颗粒细胞和卵巢片段对类固醇生成的影响存在差异,这表明这些肽可同时靶向颗粒细胞和卵巢细胞。
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引用次数: 0
Enhancing endometrial receptivity: the roles of human chorionic gonadotropin in autophagy and apoptosis regulation in endometrial stromal cells 增强子宫内膜的接受能力:人绒毛膜促性腺激素在子宫内膜基质细胞自噬和凋亡调控中的作用
IF 4.4 2区 医学 Q1 Medicine Pub Date : 2024-04-04 DOI: 10.1186/s12958-024-01205-x
Bin Wang, Mingxia Gao, Ying Yao, Haofei Shen, Hongwei Li, Jingjing Sun, Liyan Wang, Xuehong Zhang
Inadequate endometrial receptivity often results in embryo implantation failure and miscarriage. Human chorionic gonadotropin (hCG) is a key signaling molecule secreted during early embryonic development, which regulates embryonic maternal interface signaling and promotes embryo implantation. This study aimed to examine the impact of hCG on endometrial receptivity and its underlying mechanisms. An exploratory study was designed, and endometrial samples were obtained from women diagnosed with simple tubal infertility or male factor infertile (n = 12) and recurrent implantation failure (RIF, n = 10). Using reverse transcription-quantitative PCR and western blotting, luteinizing hormone (LH)/hCG receptor (LHCGR) levels and autophagy were detected in the endometrial tissues. Subsequently, primary endometrial stromal cells (ESCs) were isolated from these control groups and treated with hCG to examine the presence of LHCGR and markers of endometrial receptivity (HOXA10, ITGB3, FOXO1, LIF, and L-selectin ligand) and autophagy-related factors (Beclin1, LC3, and P62). The findings revealed that the expressions of receptivity factors, LHCGR, and LC3 were reduced in the endometrial tissues of women with RIF compared with the control group, whereas the expression of P62 was elevated. The administration of hCG to ESCs specifically activated LHCGR, stimulating an increase in the endometrial production of HOXA10, ITGB3, FOXO1, LIF and L-selectin ligands. Furthermore, when ESCs were exposed to 0.1 IU/mL hCG for 72 h, the autophagy factors Beclin1 and LC3 increased within the cells and P62 decreased. Moreover, the apoptotic factor Bax increased and Bcl-2 declined. However, when small interfering RNA was used to knock down LHCGR, hCG was less capable of controlling endometrial receptivity and autophagy molecules in ESCs. In addition, hCG stimulation enhanced the phosphorylation of ERK1/2 and mTOR proteins. These results suggest that women with RIF exhibit lower levels of LHCGR and compromised autophagy function in their endometrial tissues. Thus, hCG/LHCGR could potentially improve endometrial receptivity by modulating autophagy and apoptosis.
子宫内膜接受能力不足往往会导致胚胎植入失败和流产。人绒毛膜促性腺激素(hCG)是胚胎早期发育过程中分泌的一种关键信号分子,可调节胚胎母体界面信号传导并促进胚胎着床。本研究旨在探讨 hCG 对子宫内膜接受性的影响及其内在机制。研究人员设计了一项探索性研究,从被诊断为单纯输卵管性不孕或男性因素不孕(12 人)和复发性着床失败(10 人)的女性中获取子宫内膜样本。通过反转录定量 PCR 和 Western 印迹技术,检测了子宫内膜组织中黄体生成素(LH)/hCG 受体(LHCGR)的水平和自噬作用。随后,从这些对照组中分离出原代子宫内膜基质细胞(ESCs),并用 hCG 处理,以检测 LHCGR 和子宫内膜接受性标记物(HOXA10、ITGB3、FOXO1、LIF 和 L 选择素配体)以及自噬相关因子(Beclin1、LC3 和 P62)的存在。研究结果表明,与对照组相比,RIF 妇女的子宫内膜组织中接受因子、LHCGR 和 LC3 的表达量减少,而 P62 的表达量升高。给 ESCs 注射 hCG 可特异性激活 LHCGR,刺激子宫内膜产生更多的 HOXA10、ITGB3、FOXO1、LIF 和 L 选择素配体。此外,当将 ESCs 暴露于 0.1 IU/mL hCG 72 小时后,细胞内的自噬因子 Beclin1 和 LC3 增加,P62 减少。此外,细胞凋亡因子Bax增加,Bcl-2减少。然而,当使用小干扰 RNA 敲除 LHCGR 时,hCG 对 ESCs 中子宫内膜接受性和自噬分子的控制能力减弱。此外,hCG 刺激增强了 ERK1/2 和 mTOR 蛋白的磷酸化。这些结果表明,RIF 妇女的子宫内膜组织中 LHCGR 水平较低,自噬功能受损。因此,hCG/LHCGR 有可能通过调节自噬和细胞凋亡来改善子宫内膜的接受能力。
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引用次数: 0
Map-1a regulates Sertoli cell BTB dynamics through the cytoskeletal organization of microtubule and F-actin Map-1a通过微管和F-肌动蛋白的细胞骨架组织调控Sertoli细胞BTB动力学
IF 4.4 2区 医学 Q1 Medicine Pub Date : 2024-04-03 DOI: 10.1186/s12958-024-01204-y
Lingling Wang, Ming Yan, Tiao Bu, Xiaolong Wu, Linxi Li, Bruno Silvestrini, Fei Sun, C. Yan Cheng, Hao Chen
Microtubule-associated protein 1a (Map1a) is a microtubule (MT) regulatory protein that binds to the MT protofilaments in mammalian cells to promote MT stabilization. Maps work with MT cleavage proteins and other MT catastrophe-inducing proteins to confer MT dynamics to support changes in the Sertoli cell shape to sustain spermatogenesis. However, no functional studies are found in the literature to probe its role in spermatogenesis. Using an RNAi approach, coupled with the use of toxicant-induced testis (in vivo)- and Sertoli cell (in vitro)-injury models, RNA-Seq analysis, transcriptome profiling, and relevant bioinformatics analysis, immunofluorescence analysis, and pertinent biochemical assays for cytoskeletal organization, we have delineated the functional role of Map1a in Sertoli cells and testes. Map1a was shown to support MT structural organization, and its knockdown (KD) also perturbed the structural organization of actin, vimentin, and septin cytoskeletons as these cytoskeletons are intimately related, working in concert to support spermatogenesis. More importantly, cadmium-induced Sertoli cell injury that perturbed the MT structural organization across the cell cytoplasm was associated with disruptive changes in the distribution of Map1a and a surge in p-p38-MAPK (phosphorylated p38-mitogen-activated protein kinase) expression but not total p38-MAPK. These findings thus support the notion that p-p38-MAPK activation is involved in cadmium-induced Sertoli cell injury. This conclusion was supported by studies using doramapimod, a specific p38-MAPK phosphorylation (activation) inhibitor, which was capable of restoring the cadmium-induced disruptive structural organization of MTs across the Sertoli cell cytoplasm. In summary: this study provides mechanistic insights regarding restoration of toxicant-induced Sertoli cell and testis injury and male infertility.
微管相关蛋白 1a(Map1a)是一种微管(MT)调节蛋白,可与哺乳动物细胞中的 MT 原丝结合,促进 MT 的稳定。Map1a与MT裂解蛋白和其他MT灾难诱导蛋白共同作用,赋予MT活力,以支持Sertoli细胞形状的变化,从而维持精子发生。然而,目前还没有文献对其在精子发生过程中的作用进行功能性研究。我们利用 RNAi 方法,并结合使用毒物诱导的睾丸(体内)和 Sertoli 细胞(体外)损伤模型、RNA-Seq 分析、转录组图谱分析和相关生物信息学分析、免疫荧光分析以及细胞骨架组织的相关生化检测,确定了 Map1a 在 Sertoli 细胞和睾丸中的功能作用。研究表明,Map1a支持MT结构组织,其敲除(KD)也会扰乱肌动蛋白、波形蛋白和septin细胞骨架的结构组织,因为这些细胞骨架密切相关,共同支持精子发生。更重要的是,镉诱导的 Sertoli 细胞损伤扰乱了整个细胞胞质的 MT 结构组织,这与 Map1a 分布的破坏性变化和 p-p38-MAPK(磷酸化 p38-中性粒细胞活化蛋白激酶)表达的激增有关,但与 p38-MAPK 的总量无关。因此,这些发现支持了 p-p38-MAPK 激活参与镉诱导的 Sertoli 细胞损伤的观点。使用多拉帕莫德(一种特异性 p38-MAPK 磷酸化(活化)抑制剂)进行的研究支持了这一结论,多拉帕莫德能够恢复镉诱导的整个 Sertoli 细胞质中 MT 的破坏性结构组织。综上所述:这项研究为恢复毒物诱导的Sertoli细胞和睾丸损伤以及男性不育症提供了机理上的启示。
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引用次数: 0
Reproductive outcomes of dual trigger therapy with GnRH agonist and hCG versus hCG trigger in women with diminished ovarian reserve: a retrospective study 卵巢储备功能减退妇女接受 GnRH 激动剂和 hCG 双触发疗法与 hCG 触发疗法的生殖效果:一项回顾性研究
IF 4.4 2区 医学 Q1 Medicine Pub Date : 2024-04-02 DOI: 10.1186/s12958-024-01211-z
Kai Chen, Chunmei Zhang, Lixue Chen, Yue Zhao, Hongzhen Li
Diminished ovarian reserve (DOR) is one of the obstacles affecting the reproductive outcomes of patients receiving assisted reproductive therapy. The purpose of this study was to investigate whether dual trigger, including gonadotropin‐releasing hormone agonist (GnRHa) and human chorionic gonadotropin (hCG), can improve pregnancy outcomes in patients with DOR undergoing in vitro fertilization (IVF) cycles using mild stimulation protocols. A total of 734 patients with DOR were included in this retrospective study. Patients were divided into a recombinant hCG trigger group and a dual trigger group (hCG combined with GnRHa) according to the different trigger drugs used. The main outcome measures included the number of oocytes retrieved, the fertilization rate, the number of transferable embryos, the implantation rate, the clinical pregnancy rate, the miscarriage rate, the live birth rate (LBR), and the cumulative live birth rate (CLBR). Generalized linear model and logistic regression analyses were performed for confounding factors. There were 337 cycles with a single hCG trigger and 397 cycles with dual trigger. The dual trigger group demonstrated significantly higher numbers of retrieved oocytes [3.60 vs. 2.39, adjusted β = 0.538 (0.221–0.855)], fertilized oocytes [2.55 vs. 1.94, adjusted β = 0.277 (0.031–0.523)] and transferable embryos [1.22 vs. 0.95, adjusted β = 0.162 (-0.005–0.329)] than did the hCG trigger group, whereas no significant difference in the fertilization rate was observed between the two groups. Moreover, the embryo transfer cancellation rate (35.5% vs. 43.9%) was obviously lower in the dual trigger group. Among the fresh embryo transfer cycles, the implantation rate, clinical pregnancy rate, miscarriage rate and live birth rate were similar between the two groups. After controlling for potential confounding variables, the trigger method was identified as an independent factor affecting the number of oocytes retrieved but had no significant impact on the CLBR. Dual triggering of final oocyte maturation with hCG combined with GnRHa can significantly increase the number of oocytes retrieved in patients with DOR but has no improvement effect on the implantation rate, clinical pregnancy rate or LBR of fresh cycles or on the CLBR.
卵巢储备功能减退(DOR)是影响接受辅助生殖治疗患者生殖结果的障碍之一。本研究旨在探讨促性腺激素释放激素激动剂(GnRHa)和人绒毛膜促性腺激素(hCG)的双重触发是否能改善接受体外受精(IVF)周期的DOR患者的妊娠结局。这项回顾性研究共纳入了 734 名 DOR 患者。根据所使用的不同触发药物,患者被分为重组hCG触发组和双触发组(hCG与GnRHa联合)。主要结果指标包括取卵数、受精率、可移植胚胎数、植入率、临床妊娠率、流产率、活产率(LBR)和累积活产率(CLBR)。针对混杂因素进行了广义线性模型和逻辑回归分析。有 337 个周期采用单一 hCG 触发,397 个周期采用双重触发。双触发组的取卵数[3.60 对 2.39,调整后 β = 0.538 (0.221-0.855)]、受精卵数[2.55 对 1.94,调整后 β = 0.277 (0.031-0.523)]和可移植胚胎数均明显高于单触发组。523)]和可移植胚胎[1.22 vs. 0.95,调整后 β = 0.162(-0.005-0.329)]。此外,双触发组的胚胎移植取消率(35.5% 对 43.9%)明显较低。在新鲜胚胎移植周期中,两组的植入率、临床妊娠率、流产率和活产率相似。在控制了潜在的混杂变量后,发现触发方法是影响取卵数的一个独立因素,但对 CLBR 没有显著影响。用 hCG 联合 GnRHa 双重触发最终卵母细胞成熟可显著增加 DOR 患者取回的卵母细胞数量,但对新鲜周期的着床率、临床妊娠率或 LBR 或 CLBR 没有改善作用。
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引用次数: 0
Survival in pregnancy-associated breast cancer patients compared to non-pregnant controls. 与非妊娠对照组相比,妊娠相关乳腺癌患者的生存率。
IF 4.4 2区 医学 Q1 Medicine Pub Date : 2024-03-26 DOI: 10.1186/s12958-024-01206-w
María Martín Cameán, Ibon Jaunarena, Jose Ignacio Sánchez-Méndez, Covadonga Martín, Félix Boria, Elena Martín, Emanuela Spagnolo, Ignacio Zapardiel, Alicia Hernández Gutiérrez

Background: Pregnancy-associated breast cancer (PABC) is a rare entity whose prognosis has previously been studied and is subject to controversy.

Methods: Survival of patients with PABC diagnosed between 2009 and 2021 with breast cancer during pregnancy or until 1 year after childbirth was compared with non-pregnant patients with breast cancer from the same period at La Paz University Hospital. Cox proportional hazards regression was used to compare disease-free (DFS) and overall (OS) survival between the groups, adjusting for grade and pathologic stage.

Results: Among the 89 included patients with breast cancer, 34 were diagnosed during pregnancy, and 55 were not pregnant. The pregnant patients were more likely to have grade 3 tumors (61.3% vs 37%, p = 0.023) and an advanced stage (pathologic stage III-IV: 44.1% vs 17.6%, p = 0.008). Median follow-up was 47 months for the pregnant group and 46 months for the control group. After adjustments for tumor grade and pathologic stage, OS was comparable between the groups (HR 2.03; 95% CI 0.61 to 6.79; P = 0.25).

Conclusions: The outcome of women diagnosed with PABC is comparable to young non-pregnant controls. However, it should be taken into account that PABC has a more aggressive phenotype.

背景:妊娠相关性乳腺癌(PABC妊娠相关性乳腺癌(PABC)是一种罕见的乳腺癌,其预后曾有过研究,但一直存在争议:方法:将拉巴斯大学医院在2009年至2021年期间确诊的妊娠期或产后1年前的PABC乳腺癌患者的生存率与同期非妊娠期乳腺癌患者的生存率进行比较。在调整分级和病理分期后,采用 Cox 比例危险度回归法比较两组患者的无病生存期(DFS)和总生存期(OS):在89名乳腺癌患者中,34人在怀孕期间确诊,55人未怀孕。怀孕患者更有可能患有3级肿瘤(61.3%对37%,P = 0.023)和晚期(病理分期III-IV:44.1%对17.6%,P = 0.008)。妊娠组的中位随访时间为47个月,对照组为46个月。在对肿瘤分级和病理分期进行调整后,两组的OS相当(HR 2.03;95% CI 0.61至6.79;P = 0.25):结论:确诊为PABC的妇女的预后与年轻的非妊娠对照组相当。结论:确诊为PABC的女性患者的预后与年轻的非妊娠对照组相当,但应考虑到PABC的表型更具侵袭性。
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引用次数: 0
A modern-day litmus test for the sustainability of daily IVF practice - Alabama supreme court ruling overreaches in asserting that frozen embryos are legally children. 试管婴儿日常实践可持续发展的现代试金石--阿拉巴马州最高法院的裁决过度主张冷冻胚胎在法律上是儿童。
IF 4.4 2区 医学 Q1 Medicine Pub Date : 2024-03-21 DOI: 10.1186/s12958-024-01201-1
David B Seifer
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引用次数: 0
Liraglutide improved the reproductive function of obese mice by upregulating the testicular AC3/cAMP/PKA pathway 利拉鲁肽通过上调睾丸 AC3/cAMP/PKA 通路改善肥胖小鼠的生殖功能
IF 4.4 2区 医学 Q1 Medicine Pub Date : 2024-03-20 DOI: 10.1186/s12958-024-01202-0
Ruibing Qi, Yuzhen Liang, Jinming Yu, Bing Chen, Jiaqin Jiang, Xingye Wu, Wensheng Lu, Zhengming Li
The incidence of male reproductive dysfunction is increasing annually, and many studies have shown that obesity can cause severe harm to male reproductive function. The mechanism of male reproductive dysfunction caused by obesity is unclear, and there is no ideal treatment. Identification of effective therapeutic drugs and elucidation of the molecular mechanism involved in male reproductive health are meaningful. In this study, we investigated the effects of the GLP-1 receptor agonist liraglutide on sex hormones, semen quality, and testicular AC3/cAMP/PKA levels in high-fat-diet-induced obese mice. Obese mice and their lean littermates were treated with liraglutide or saline for 12 weeks. Body weight was measured weekly. Fasting blood glucose (FBG) was measured using a blood glucose test strip. The serum levels of insulin (INS), luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T), free testosterone (F-TESTO), estradiol (E2), and sex hormone binding globulin (SHBG) were detected using ELISA. The sperm morphology and sperm count were observed after Pap staining. The mRNA and protein expression levels of testicular GLP-1R and AC3 were measured by RT-qPCR and Western blot, respectively. Testicular cAMP levels and PKA activity were detected using ELISA. Liraglutide treatment can decrease body weight, FBG, INS, HOMA-IR, E2 and SHBG levels; increase LH, FSH, T, and F-TESTO levels; increase sperm count; decrease the sperm abnormality rate; and increase GLP-1R and AC3 expression levels and cAMP levels and PKA activity in testicular tissue. Liraglutide can improve the sex hormone levels and semen quality of obese male mice. In addition to its weight loss effect, liraglutide can improve the reproductive function of obese male mice, which may also be related to the upregulation of AC3/cAMP/PKA pathway in the testis. This work lays the groundwork for future clinical studies.
男性生殖功能障碍的发病率逐年上升,许多研究表明,肥胖会对男性生殖功能造成严重危害。肥胖导致男性生殖功能障碍的机制尚不清楚,也没有理想的治疗方法。找到有效的治疗药物,阐明男性生殖健康的分子机制是非常有意义的。本研究探讨了 GLP-1 受体激动剂利拉鲁肽对高脂饮食诱导的肥胖小鼠性激素、精液质量和睾丸 AC3/cAMP/PKA 水平的影响。肥胖小鼠及其瘦小同窝鼠接受利拉鲁肽或生理盐水治疗 12 周。每周测量一次体重。使用血糖试纸测量空腹血糖(FBG)。用酶联免疫吸附法检测血清中胰岛素(INS)、黄体生成素(LH)、促卵泡激素(FSH)、睾酮(T)、游离睾酮(F-TESTO)、雌二醇(E2)和性激素结合球蛋白(SHBG)的水平。巴氏染色后观察精子形态和精子数量。通过 RT-qPCR 和 Western 印迹分别检测了睾丸 GLP-1R 和 AC3 的 mRNA 和蛋白表达水平。ELISA 检测了睾丸 cAMP 水平和 PKA 活性。利拉鲁肽治疗可降低体重、FBG、INS、HOMA-IR、E2和SHBG水平;提高LH、FSH、T和F-TESTO水平;增加精子数量;降低精子畸形率;提高睾丸组织中GLP-1R和AC3的表达水平、cAMP水平和PKA活性。利拉鲁肽能改善肥胖雄性小鼠的性激素水平和精液质量。除了减肥效果外,利拉鲁肽还能改善肥胖雄性小鼠的生殖功能,这可能也与AC3/cAMP/PKA通路在睾丸中的上调有关。这项研究为今后的临床研究奠定了基础。
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引用次数: 0
Predictive models of recurrent implantation failure in patients receiving ART treatment based on clinical features and routine laboratory data 基于临床特征和常规实验室数据的抗逆转录病毒疗法患者复发植入失败预测模型
IF 4.4 2区 医学 Q1 Medicine Pub Date : 2024-03-20 DOI: 10.1186/s12958-024-01203-z
Qunying Fang, Zonghui Qiao, Lei Luo, Shun Bai, Min Chen, Xiangjun Zhang, Lu Zong, Xian-hong Tong, Li-min Wu
The objective was to construct a model for predicting the probability of recurrent implantation failure (RIF) after assisted reproductive technology (ART) treatment based on the clinical characteristics and routine laboratory test data of infertile patients. A model was developed to predict RIF. The model showed high calibration in external validation, helped to identify risk factors for RIF, and improved the efficacy of ART therapy. Research on the influencing factors of RIF has focused mainly on embryonic factors, endometrial receptivity, and immune factors. However, there are many kinds of examinations regarding these aspects, and comprehensive screening is difficult because of the limited time and economic conditions. Therefore, we should try our best to analyse the results of routine infertility screenings to make general predictions regarding the occurrence of RIF. A retrospective study was conducted with 5212 patients at the Reproductive Center of the First Affiliated Hospital of USTC from January 2018 to June 2022. This study included 462 patients in the RIF group and 4750 patients in the control group. The patients’ basic characteristics, clinical treatment data, and laboratory test indices were compared. Logistic regression was used to analyse RIF-related risk factors, and the prediction model was evaluated by receiver operating characteristic (ROC) curves and the corresponding areas under the curve (AUCs). Further analysis of the influencing factors of live births in the first cycle of subsequent assisted reproduction treatment in RIF patients was performed, including the live birth subgroup (n = 116) and the no live birth subgroup (n = 200). (1) An increased duration of infertility (1.978; 95% CI, 1.264–3.097), uterine cavity abnormalities (2.267; 95% CI, 1.185–4.336), low AMH levels (0.504; 95% CI, 0.275–0.922), insulin resistance (3.548; 95% CI, 1.931–6.519), antinuclear antibody (ANA)-positive status (3.249; 95% CI, 1.20-8.797) and anti-β2-glycoprotein I antibody (A-β2-GPI Ab)-positive status (5.515; 95% CI, 1.481–20.536) were associated with an increased risk of RIF. The area under the curve of the logistic regression model was 0.900 (95% CI, 0.870–0.929) for the training cohort and 0.895 (95% CI, 0.865–0.925) for the testing cohort. (2) Advanced age (1.069; 95% CI, 1.015–1.126) was a risk factor associated with no live births after the first cycle of subsequent assisted reproduction treatment in patients with RIF. Blastocyst transfer (0.365; 95% CI = 0.181–0.736) increased the probability of live birth in subsequent cycles in patients with RIF. The area under the curve of the logistic regression model was 0.673 (95% CI, 0.597–0.748). This was a single-centre regression study, for which the results need to be evaluated and verified by prospective large-scale randomized controlled studies. The small sample size for the analysis of factors influencing pregnancy outcomes in subsequent assisted reproduction cycles for RIF patients res
目的是根据不孕不育患者的临床特征和常规实验室检查数据,建立一个模型来预测辅助生殖技术(ART)治疗后再次植入失败(RIF)的概率。我们建立了一个预测 RIF 的模型。该模型在外部验证中显示出较高的校准性,有助于识别 RIF 的风险因素,并提高 ART 治疗的疗效。对 RIF 影响因素的研究主要集中在胚胎因素、子宫内膜接受性和免疫因素上。然而,这些方面的检查种类繁多,由于时间和经济条件的限制,全面筛查比较困难。因此,我们应尽量分析常规不孕症筛查的结果,对 RIF 的发生做出大致预测。2018年1月至2022年6月,中国科学技术大学附属第一医院生殖中心对5212名患者进行了回顾性研究。该研究包括RIF组462例患者和对照组4750例患者。比较了患者的基本特征、临床治疗数据和实验室检查指标。采用逻辑回归分析 RIF 相关风险因素,并通过接收器操作特征曲线(ROC)和相应的曲线下面积(AUC)对预测模型进行评估。进一步分析了RIF患者后续辅助生殖治疗第一周期活产的影响因素,包括活产亚组(n = 116)和无活产亚组(n = 200)。519)、抗核抗体(ANA)阳性状态(3.249;95% CI,1.20-8.797)和抗β2-糖蛋白 I 抗体(A-β2-GPI Ab)阳性状态(5.515;95% CI,1.481-20.536)与 RIF 风险增加相关。训练队列的逻辑回归模型曲线下面积为 0.900(95% CI,0.870-0.929),测试队列的曲线下面积为 0.895(95% CI,0.865-0.925)。(2)高龄(1.069;95% CI,1.015-1.126)是 RIF 患者后续辅助生殖治疗第一周期后无活产的相关风险因素。囊胚移植(0.365;95% CI = 0.181-0.736)增加了 RIF 患者后续周期的活产概率。逻辑回归模型的曲线下面积为 0.673(95% CI,0.597-0.748)。这是一项单中心回归研究,其结果需要通过前瞻性大规模随机对照研究进行评估和验证。RIF患者后续辅助生殖周期妊娠结局影响因素分析的样本量较小,因此纳入的协变量较少,今后的研究需要更大的样本量和纳入更多的因素来进行评估和验证。在胚胎移植前预测胚胎植入情况将有助于患者的临床管理和疾病预测,并进一步改善 ART 治疗效果。本研究得到国家自然科学基金一般项目(82201792、82301871、81971446、82374212)和安徽省自然科学基金(2208085MH206)的资助。本研究无利益冲突。本研究已在中国临床试验注册中心注册(临床试验编号:ChiCTR1800018298)。
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引用次数: 0
Pregnancy and obstetric outcomes of dichorionic triamniotic triplet pregnancies with selective foetal reduction after assisted reproductive technology. 通过辅助生殖技术选择性减胎的二绒毛膜三羊水三胞胎妊娠的妊娠和产科结果。
IF 4.4 2区 医学 Q1 Medicine Pub Date : 2024-03-15 DOI: 10.1186/s12958-024-01199-6
Shuhua Liu, Qianhua Xu, Dehong Liu, Qiuru Li, Jingyu Qian, Bin Zhang, Xianxia Chen

Background: It is generally beneficial and recommended that dichorionic triamniotic (DCTA) triplet pregnancies be reduced to monochorionic (MC) twin or singleton pregnancies after assisted reproductive technology (ART). However, some infertile couples still have a firm desire to retain twins. For this reason, the best foetal reduction strategies need to be available for infertile couples and clinicians. Given that data on the elective reduction of DCTA triplet pregnancies to twin pregnancies are scarce, we investigated the outcomes of elective reduction of DCTA triplet pregnancies through the retrospective analysis of previous data.

Method: Patients with DCTA triplet pregnancies who underwent elective foetal reduction between January 2012 and June 2020 were recruited. A total of 67 eligible patients with DCTA triplet pregnancies were divided into two groups: a DCTA-to-dichorionic diamniotic (DCDA) twin group (n = 38) and a DCTA-to-monochorionic diamniotic (MCDA) twin group (n = 29); the basic clinical data of the two groups were collected for comparison.

Results: Compared with the DCDA-to-MCDA twin group, the DCTA-to-DCDA twin group had lower rates of complete miscarriage (7.89% versus 31.03%, p = 0.014), early complete miscarriage (5.26% versus 24.14%, p = 0.034), late preterm birth (25.71% versus 65.00%, p = 0.009) and very low birth weight (0 versus 11.11%, p = 0.025). In addition, the DCTA-to-DCDA twin group had higher rates of full-term delivery (65.71% versus 25.00%, p = 0.005), survival (92.11% versus 68.97%, p = 0.023), and taking the babies home (92.11% versus 68.97%, p = 0.023) than did the DCTA-to-MCDA twin group. In terms of neonatal outcomes, a significantly greater gestational age (38.06 ± 2.39 versus 36.28 ± 2.30, p = 0.009), average birth weight (3020.77 ± 497.33 versus 2401.39 ± 570.48, p < 0.001), weight of twins (2746.47 ± 339.64 versus 2251.56 ± 391.26, p < 0.001), weight of the larger neonate (2832.94 ± 320.58 versus 2376.25 ± 349.95, p < 0.001) and weight of the smaller neonate (2660.00 ± 345.34 versus 2126.88 ± 400.93, p < 0.001) was observed in the DCTA-to-DCDA twin group compared to the DCTA-to-MCDA twin group.

Conclusion: The DCTA-to-DCDA twin group had better pregnancy and neonatal outcomes than the DCTA-to-MCDA twin group. This reduction approach may be beneficial for patients with dichorionic triamniotic triplet pregnancies who have a strong desire to have DCDA twins.

背景:一般来说,辅助生殖技术(ART)后,将二绒毛膜三羊膜(DCTA)三胞胎妊娠减少为单绒毛膜(MC)双胎或单胎妊娠是有益的,也是值得推荐的。然而,一些不孕夫妇仍有保留双胞胎的强烈愿望。因此,不孕夫妇和临床医生需要掌握最佳的减胎策略。鉴于将 DCTA 三胞胎妊娠选择性减胎为双胎妊娠的数据很少,我们通过对以往数据的回顾性分析,研究了 DCTA 三胞胎妊娠选择性减胎的结果:方法:招募2012年1月至2020年6月期间接受选择性减胎术的DCTA三胞胎妊娠患者。将符合条件的 67 例 DCTA 三胎妊娠患者分为两组:DCTA 对二绒毛膜双胎(DCDA)组(38 例)和 DCTA 对单绒毛膜双胎(MCDA)组(29 例);收集两组患者的基本临床数据进行比较:与 DCDA 对 MCDA 双胎组相比,DCTA 对 DCDA 双胎组的完全流产率(7.89% 对 31.03%,P = 0.014)、早期完全流产率(5.26% 对 24.14%,P = 0.034)、晚期早产率(25.71% 对 65.00%,P = 0.009)和极低出生体重率(0 对 11.11%,P = 0.025)均较低。此外,DCTA 对 DCDA 双胎组的足月分娩率(65.71% 对 25.00%,p = 0.005)、存活率(92.11% 对 68.97%,p = 0.023)和婴儿回家率(92.11% 对 68.97%,p = 0.023)均高于 DCTA 对 MCDA 双胎组。DCTA对DCDA双胎组的妊娠和新生儿结局优于DCTA对MCDA双胎组。这种减胎法可能对强烈希望生下 DCDA 双胞胎的二绒毛膜三羊膜三胞胎妊娠患者有益。
{"title":"Pregnancy and obstetric outcomes of dichorionic triamniotic triplet pregnancies with selective foetal reduction after assisted reproductive technology.","authors":"Shuhua Liu, Qianhua Xu, Dehong Liu, Qiuru Li, Jingyu Qian, Bin Zhang, Xianxia Chen","doi":"10.1186/s12958-024-01199-6","DOIUrl":"10.1186/s12958-024-01199-6","url":null,"abstract":"<p><strong>Background: </strong>It is generally beneficial and recommended that dichorionic triamniotic (DCTA) triplet pregnancies be reduced to monochorionic (MC) twin or singleton pregnancies after assisted reproductive technology (ART). However, some infertile couples still have a firm desire to retain twins. For this reason, the best foetal reduction strategies need to be available for infertile couples and clinicians. Given that data on the elective reduction of DCTA triplet pregnancies to twin pregnancies are scarce, we investigated the outcomes of elective reduction of DCTA triplet pregnancies through the retrospective analysis of previous data.</p><p><strong>Method: </strong>Patients with DCTA triplet pregnancies who underwent elective foetal reduction between January 2012 and June 2020 were recruited. A total of 67 eligible patients with DCTA triplet pregnancies were divided into two groups: a DCTA-to-dichorionic diamniotic (DCDA) twin group (n = 38) and a DCTA-to-monochorionic diamniotic (MCDA) twin group (n = 29); the basic clinical data of the two groups were collected for comparison.</p><p><strong>Results: </strong>Compared with the DCDA-to-MCDA twin group, the DCTA-to-DCDA twin group had lower rates of complete miscarriage (7.89% versus 31.03%, p = 0.014), early complete miscarriage (5.26% versus 24.14%, p = 0.034), late preterm birth (25.71% versus 65.00%, p = 0.009) and very low birth weight (0 versus 11.11%, p = 0.025). In addition, the DCTA-to-DCDA twin group had higher rates of full-term delivery (65.71% versus 25.00%, p = 0.005), survival (92.11% versus 68.97%, p = 0.023), and taking the babies home (92.11% versus 68.97%, p = 0.023) than did the DCTA-to-MCDA twin group. In terms of neonatal outcomes, a significantly greater gestational age (38.06 ± 2.39 versus 36.28 ± 2.30, p = 0.009), average birth weight (3020.77 ± 497.33 versus 2401.39 ± 570.48, p < 0.001), weight of twins (2746.47 ± 339.64 versus 2251.56 ± 391.26, p < 0.001), weight of the larger neonate (2832.94 ± 320.58 versus 2376.25 ± 349.95, p < 0.001) and weight of the smaller neonate (2660.00 ± 345.34 versus 2126.88 ± 400.93, p < 0.001) was observed in the DCTA-to-DCDA twin group compared to the DCTA-to-MCDA twin group.</p><p><strong>Conclusion: </strong>The DCTA-to-DCDA twin group had better pregnancy and neonatal outcomes than the DCTA-to-MCDA twin group. This reduction approach may be beneficial for patients with dichorionic triamniotic triplet pregnancies who have a strong desire to have DCDA twins.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10941449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140140635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Reproductive Biology and Endocrinology
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