Systems Biology in Reproductive Medicine最新文献_第9页

High throughput deep proteomic analysis of seminal plasma from stallions with contrasting semen quality 精液质量对比种马精浆的高通量深层蛋白质组学分析

IF 2.4 4区医学 Q1 Medicine

Systems Biology in Reproductive Medicine

Pub Date : 2022-04-28 DOI: 10.1080/19396368.2022.2057257

T. Talluri, A. Kumaresan, N. Paul, M. Sinha, John Peter Ebenezer Samuel King, K. Elango, Ankur Sharma, Kathan Raval, R. Legha, Y. Pal

Abstract Seminal plasma proteins and pathways associated with sperm motility have not been elucidated in stallions. Therefore, in the current study, using the high throughput LC/MS-MS approach, we profiled stallion seminal plasma proteins and identified the proteins and pathways associated with sperm motility. Seminal plasma from six stallions producing semen with contrasting sperm motility (n = 3 each high-and low-motile group) was utilized for proteomic analysis. We identified a total of 1687 proteins in stallion seminal plasma, of which 1627 and 1496 proteins were expressed in high- (HM) and low- motile (LM) sperm of stallions, respectively. A total number of 1436 proteins were co-expressed in both the groups; 191 (11%) and 60 (3.5%) proteins were exclusively detected in HM and LM groups, respectively. A total of 220 proteins were upregulated (>1-fold change) and 386 proteins were downregulated in SP from LM group stallions as compared to HM group stallions, while 830 proteins were neutrally expressed in both the groups. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed dysregulation of the important proteins related to mitochondrial function, acrosome, and sperm cytoskeleton in the seminal plasma of stallions producing ejaculates with low sperm motility. High abundance of peroxiredoxins and low abundance of seminal Chaperonin Containing TCP1 Complex (CCT) complex and Annexins indicate dysregulated oxidative metabolism, which might be the underlying etiology for poor sperm motility in LM group stallions. In conclusion, the current study identified the seminal plasma proteomic alterations associated with poor sperm motility in stallions; the results indicate that poor sperm motility in stallions could be associated with altered expression of seminal plasma proteins involved in oxidative metabolism.

摘要精浆蛋白和与精子运动相关的途径尚未在种马中阐明。因此，在目前的研究中，使用高通量LC/MS-MS方法，我们对种马精浆蛋白进行了分析，并确定了与精子活力相关的蛋白和途径。六匹雄性种马的精浆产生的精液具有相反的精子活力（n = 高运动组和低运动组各3个）用于蛋白质组学分析。我们在种马精浆中共鉴定了1687种蛋白质，其中1627种和1496种蛋白质分别在种马的高（HM）和低（LM）精子中表达。在两组中共表达了1436种蛋白质；HM组和LM组分别检测到191种（11%）和60种（3.5%）蛋白质。与HM组种马相比，LM组种马的SP中共有220个蛋白质上调（变化>1倍），386个蛋白质下调，而两组中均有830个蛋白质中性表达。基因本体论和京都基因与基因组百科全书（KEGG）的分析揭示了在产生精子活力低的精液的种马的精浆中与线粒体功能、顶体和精子细胞骨架相关的重要蛋白质的失调。高丰度的过氧氧化还原酶和低丰度的含精伴侣蛋白TCP1复合物（CCT）和膜联蛋白表明氧化代谢失调，这可能是LM组种马精子运动能力差的潜在病因。总之，目前的研究确定了与种马精子运动能力差相关的精浆蛋白质组学改变；结果表明，种马精子活力低下可能与参与氧化代谢的精浆蛋白表达改变有关。

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引用次数: 2

Impact of preovulatory estradiol concentrations on subsequent luteal function in beef cattle 排卵前雌二醇浓度对肉牛后续黄体功能的影响

IF 2.4 4区医学 Q1 Medicine

Systems Biology in Reproductive Medicine

Pub Date : 2022-04-08 DOI: 10.1080/19396368.2022.2038717

M. K. McLean, T. Geary, A. Zezeski, M. Smith, T. Spencer, K. Pohler, S. Reese, G. Perry

Abstract It has been hypothesized that circulating concentrations of estradiol during the preovulatory period, can impact subsequent progesterone concentrations. Ovulation was synchronized in nonlactating beef cows (n = 53). Cows that exhibited estrus before gonadotrophin-releasing hormone (GnRH)-induced ovulation (d 0) had greater (p<.01) peak concentrations of estradiol compared with cows that did not express estrus (11.5 ± 0.8 vs. 6.2 ± 0.6 pg/mL), respectively, but there was no difference in ovulatory follicle size (p= .80) or interval from GnRH2 to ovulation (p=.23). Circulating concentrations of progesterone during luteal formation (d 3–7; p=.70 and p=.77) or mid-luteal phase (d 8–14; p=.39 and p=.12) were not affected by elevated periovulatory estradiol or an interaction with day. To investigate the direct influence of estradiol on luteal function, ovulation (d 0) was synchronized in nonlactating beef cows and cows were allocated to three groups (control, n = 5; vehicle injection, n = 4; or an estradiol antagonist (Fulvestrant; ICI 182,780), n = 4. Intrafollicular injection of vehicle (100 µL) or an estradiol antagonist (25 μg Fulvestrant in 100 µL) into the largest follicle occurred on d –2. Concentrations of estradiol increased (p<.0001) from d –2 to 0 but did not differ among groups (p>.50). Furthermore, plasma concentrations of progesterone on d 0 through 20 were not affected by treatment (p=.86). These results indicate that elevated preovulatory estradiol before ovulation was not required to prepare granulosa cells for luteinization or subsequent luteal progesterone secretion but did tend to impact luteal lifespan.

据推测，排卵前雌二醇的循环浓度会影响随后的黄体酮浓度。非泌乳肉牛的排卵同步(n = 53)。在促性腺激素释放激素(GnRH)诱导的排卵(d 0)之前表现出发情的奶牛(p.50)。此外，治疗对第0 ~ 20天血浆孕酮浓度没有影响(p= 0.86)。这些结果表明，排卵前升高的雌二醇并不需要为黄体生成或随后的黄体黄体酮分泌准备颗粒细胞，但确实倾向于影响黄体寿命。

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引用次数: 1

Epigenetic reprogramming in cloned mouse embryos following treatment with DNA methyltransferase and histone deacetylase inhibitors DNA甲基转移酶和组蛋白去乙酰化酶抑制剂处理后克隆小鼠胚胎的表观遗传重编程

IF 2.4 4区医学 Q1 Medicine

Systems Biology in Reproductive Medicine

Pub Date : 2022-04-06 DOI: 10.1080/19396368.2022.2036868

Maryam Zarei, Boshra Shamaghdari, Zeinab Vahabi, A. Dalman, P. Eftekhari Yazdi

Abstract We examined the effects of DNA methyltransferase inhibitor – RG108, and histone deacetylase inhibitor – SAHA, on the reprogramming parameters of cloned mouse embryos produced by somatic cell nuclear transfer into oocytes. The programming parameters studied included dynamics of histone reacetylation, developmental rate, DNA methylation, and transcript levels of genes, all of which are pivotal to lineage specification and blastocyst formation. At the pronuclear stage, somatic nucleus-transplanted oocytes treated with 5 µM SAHA presented higher histone acetylation at H3K9, H3K14, H4K16 and H4K12, compared to untreated clones (p < 0.05). At the morula stage, cloned embryos treated with 5 μM RG108 or 5 μM SAHA presented lower DNA methylation intensity compared to untreated clones (p < 0.05), resembling the intensity levels of fertilized embryos. However, these effects were not observed when RG108 and SAHA were used in combination. The rate of morula formation was significantly higher in cloned embryos treated with 5 µM SAHA than in untreated clones, whereas treatment with RG108 resulted in no obvious effects on morula formation rates. On the other hand, the combined treatment with RG108 and SAHA resulted in inferior rates of cloned morula formation, compared to untreated clones. At the blastocyst stage, the aberrant expression levels of key developmental genes Oct4 and Cdx2, but not Nanog, were corrected in cloned embryos by the treatment with RG108. This is similar to the intensity levels seen in fertilized embryos. The expression of Rpl7l1 gene was significantly higher in embryos treated with both RG108 and SAHA than in untreated and in control groups. In summary, the present study showed that SAHA and RG108, when applied separately, improve the rate and quality of cloned mouse embryos.

研究了DNA甲基转移酶抑制剂RG108和组蛋白去乙酰化酶抑制剂SAHA对体细胞核转移至卵母细胞的克隆小鼠胚胎重编程参数的影响。研究的编程参数包括组蛋白再乙酰化、发育速率、DNA甲基化和基因转录水平的动态，所有这些都是谱系规范和囊胚形成的关键。在原核阶段，经5µM SAHA处理的体细胞核移植卵母细胞在H3K9、H3K14、H4K16和H4K12位点的组蛋白乙酰化程度高于未处理的克隆(p < 0.05)。在桑葚胚期，5 μM RG108或5 μM SAHA处理的克隆胚胎DNA甲基化强度低于未处理的克隆胚胎(p < 0.05)，与受精胚胎的DNA甲基化强度相似。然而，当RG108和SAHA联合使用时，没有观察到这些效果。5µM SAHA处理的克隆胚胎桑葚胚形成率显著高于未处理的克隆胚胎，而RG108处理对桑葚胚形成率无明显影响。另一方面，与未处理的克隆相比，RG108和SAHA联合处理导致克隆桑葚胚形成率较低。在囊胚期，RG108可纠正克隆胚胎中关键发育基因Oct4和Cdx2的异常表达水平，而非Nanog的异常表达。这与在受精胚胎中看到的强度水平相似。RG108和SAHA处理的胚胎中Rpl7l1基因的表达明显高于未处理和对照组。综上所述，本研究表明，SAHA和RG108单独应用可提高克隆小鼠胚胎的率和质量。

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引用次数: 3

Bioethics in human embryology: the double-edged sword of embryo research 人类胚胎学中的生命伦理学:胚胎研究的双刃剑

IF 2.4 4区医学 Q1 Medicine

Systems Biology in Reproductive Medicine

Pub Date : 2022-04-05 DOI: 10.1080/19396368.2022.2052771

G. Anifandis, P. Sutovsky, P. Turek, S. Chavez, T. Kunej, C. Messini, S. Schon, A. Mavroforou, E. Adashi, S. Krawetz

Abstract There has been a significant increase in the use of assisted reproductive therapies (ARTs) over the past several decades, allowing many couples with infertility to conceive. Despite the achievements in this field, a mounting body of evidence concerning the epigenetic risks associated with ART interventions such as ovarian hormonal stimulation, intracytoplasmic sperm injection (ICSI), and in vitro culture (IVC) of oocytes and embryos has also emerged. Induced development of multiple follicles, the IVC media itself, and extended culture may alter the epigenome of both gametes and embryos, resulting in yet to be fully understood developmental, postnatal, and adult life health consequences. Investigators have attempted to decipher the molecular mechanisms mediating ART-induced epigenetic changes using either human samples or animal models with some success. As research in this field continues to expand, the ethical responsibilities of embryologists and researchers have become critically important. Here, we briefly discuss the ethical aspects of ART research, concentrating on the constraints arising from the perceived 'unnaturalness' of many of these procedures. Secondly, we focus on the bioethics and morality of human embryo research in general and how ethically acceptable model systems may be used to mimic early human embryogenesis. Lastly, we review the 14-day culture limit of human embryos and the notion that this rule could be considered of taken into account using new technologies and cues from animal models. The ‘black box’ of early post-implantation embryogenesis might be revealed using embryo models. As long as this distinct moral line has been drawn and closely followed, we should not fear scientific growth in embryo research. Although in vitro fertilization (IVF) is ethically acceptable, research with human embryos to improve its success raises serious ethical concerns that are in need of constant revisiting. Glossary index: Moral status: the ascription of obligations and rights to embryos on the basis of sentience; Sentience: the capacity of the developing embryo to experience feelings and sensations, such as the awareness of pain; Ectogenesis: the growth of the embryo in an artificial environment outside the mother's body.

摘要在过去的几十年里，辅助生殖疗法的使用显著增加，使许多不孕夫妇得以怀孕。尽管在这一领域取得了成就，但也出现了越来越多关于ART干预相关表观遗传风险的证据，如卵巢激素刺激、卵母细胞内单精子注射（ICSI）以及卵母细胞和胚胎的体外培养（IVC）。多个卵泡的诱导发育、IVC培养基本身和扩展培养可能会改变配子和胚胎的表观基因组，导致发育、出生后和成年后的健康后果尚不完全清楚。研究人员试图使用人类样本或动物模型来破译介导ART诱导的表观遗传学变化的分子机制，并取得了一些成功。随着这一领域的研究不断扩大，胚胎学家和研究人员的伦理责任变得至关重要。在这里，我们简要讨论了ART研究的伦理方面，重点讨论了其中许多程序的“不自然”所产生的限制。其次，我们关注人类胚胎研究的生物伦理和道德，以及如何使用伦理上可接受的模型系统来模拟早期人类胚胎发生。最后，我们回顾了人类胚胎的14天培养极限，以及可以使用新技术和动物模型的提示来考虑这一规则的概念。植入后早期胚胎发生的“黑匣子”可以通过胚胎模型来揭示。只要这条明确的道德线已经划定并严格遵循，我们就不应该害怕胚胎研究的科学发展。尽管体外受精（IVF）在伦理上是可以接受的，但对人类胚胎进行研究以提高其成功率，引发了严重的伦理问题，需要不断重新审视。词汇索引：道德地位：在感知的基础上对胚胎的义务和权利的归属；感觉：发育中的胚胎体验感觉和感觉的能力，例如对疼痛的感知；胚胎发育：胚胎在母体外的人工环境中生长。

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引用次数: 1

The vitrification system may affect preterm and cesarean delivery rates after single vitrified blastocyst transfer. 玻璃化系统可能影响单个玻璃化囊胚移植后的早产和剖宫产率。

IF 2.4 4区医学 Q1 Medicine

Systems Biology in Reproductive Medicine

Pub Date : 2022-04-01 Epub Date: 2021-12-09 DOI: 10.1080/19396368.2021.2005717

Yunhong Lin, Lincui Da, Shengrong Du, Qingfen Chen, Suzhu Chen, Beihong Zheng

The purpose of this study was to investigate the possible effects of different vitrification systems on single vitrified blastocyst transfer cycles. The clinical and birth outcomes of 412 patients who underwent single vitrified blastocyst transfer between January 2018 and June 2020 were retrospectively analyzed and compared between patients who underwent blastocyst vitrification with kit A (group A, 196 patients) and those who underwent blastocyst vitrification with kit B (group B, 216 patients). Clinical outcomes, including the clinical pregnancy rate, ongoing pregnancy rate, early miscarriage rate, late miscarriage rate, ectopic pregnancy rate, twin pregnancy rate, and induced labor rate due to fetal malformation, were not significantly different between the two groups (P > 0.05). The preterm delivery rate among singleton newborns (11.57% vs. 3.23%, P < 0.05) and the cesarean delivery rate were significantly higher in group B than in group A (70.25% vs. 57.26%, P < 0.05). Birth outcomes, including the male-to-female ratio, low-birth-weight rate, macrosomia rate, birth defect rate, newborn gestational age, neonatal body weight, and singleton neonatal body length, were not significantly different (P > 0.05). Our findings suggest that different vitrification systems might differentially affect birth outcomes. Such disparity could reflect differences in kit composition and/or protocol.ABBREVIATIONS: DMSO: dimethyl sulfoxide; ES: equilibration solution; VS: vitrification solution; BMI: body mass index; ICSI: intracytoplasmic sperm injection; OR: odds ratio; CI: confidence interval.

本研究的目的是探讨不同的玻璃化系统对单个玻璃化囊胚移植周期的可能影响。回顾性分析了2018年1月至2020年6月期间412例接受单一玻璃化囊胚移植的患者的临床和分娩结果，并比较了使用kit A进行囊胚玻璃化治疗的患者(A组，196例)和使用kit B进行囊胚玻璃化治疗的患者(B组，216例)。两组临床妊娠率、持续妊娠率、早期流产率、晚期流产率、异位妊娠率、双胎妊娠率、胎儿畸形引产率比较，差异均无统计学意义(P > 0.05)。单胎新生儿早产率(11.57%∶3.23%，P < 0.05)。我们的研究结果表明，不同的玻璃化系统可能会对出生结果产生不同的影响。这种差异可能反映了试剂盒组成和/或方案的差异。缩写:DMSO:二甲基亚砜;ES:平衡溶液;VS:玻璃化溶液;BMI:身体质量指数;胞浆内单精子注射;OR:优势比;CI:置信区间。

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引用次数: 0

Evaluation of the role of thiol / disulfide homeostasis in the etiology of idiopathic male infertility with a novel and automated assay. 评估硫醇/二硫稳态在特发性男性不育症病因学中的作用与一种新的和自动分析。

IF 2.4 4区医学 Q1 Medicine

Systems Biology in Reproductive Medicine

Pub Date : 2022-04-01 Epub Date: 2021-12-10 DOI: 10.1080/19396368.2021.2003481

Uygar Micoogullari, Mehmet Caglar Cakici, Furkan Umut Kilic, Erdem Kisa, Burak Ozcift, Alper Caglayan, Salim Neselioglu, Omer Faruk Karatas, Ozcan Erel

Idiopathic male infertility (IMI) is the absence of a reason to explain a patient's infertility, and it occurs at a frequency of %31. In this study we aimed to investigate the oxidant/antioxidant status of patients with IMI and compare their results to those of healthy controls.A total of 79 patients with IMI (group 1) and 90 healthy individuals (group 2) were included in the study. We used Erel & Neşelioğlu's thiol/disulfide homeostasis test. Collective and individual measurements of oxidative/antioxidative balance components were carried out by this novel thiol/disulfide homeostasis test. Serum antioxidant (total thiol (toSH), native thiol (SH)) and oxidant (disulfide (SS)) levels of all study participants were measured. The results from both groups were compared and analyzed statistically. After toSH, SH, and SS levels were determined, SS/toSH% and SS/SH% levels for each group were analyzed separately and compared statistically.The toSH, SH levels, and SS/SH%, SS/toSH% ratios were significantly different between the groups (p < 0.05).While antioxidant parameters (toSH and SH values) decreased in group1, oxidant parameters (SS/SH%, SS/toSH%) increased significantly. Although SS values were higher in group 1, the difference was not significant (p = 0.214). The SH cutoff value of 507.15 µmol/L predicted the probability of IMI development with 72.2% sensitivity and 74.4% specificity and toSH cutoff value of 545.45 µmol/L predicted IMI development with 70.9% sensitivity and 73.3 specificity (p < 0.001). Multivariate logistic regression analysis showed that the only independent risk factor for the development of IMI is SH. Patients with IMI had a significant change in their thiol/disulfide homeostasis, which suggests the involvement of this imbalance in the pathophysiology of IMI. Furthermore, these results also support the notion of the involvement of oxidative stress in sperm dysfunction. It also points to the possibility of using antioxidants in IMI treatment.Abbreviations: IMI: idiopathic male infertility; toSH: total thiol; SH: native thiol; SS: disulfide; OS: oxidative stress; ROS: reactive oxygen species; DCF: dichlorofluorescein; MiOXSYS: male infertility oxidative system; MOSI: male oxidative stress infertility; LC: L-carnitine; LAC: L-acetylcarnitine; Vit: vitamin; OAT: oligoasthenozoospermia; TMSC: total motile sperm count; WHO: World Health Organization; BMI: body mass index; DTNB: 5,5'-dithiobis-2-nitrobenzoic acid; CV: coefficient variation; ROC: receiver operating characteristic; PR: progressive, NP: non-progressive.

特发性男性不育症(IMI)是缺乏原因来解释患者的不育症，发生率为%31。在这项研究中，我们旨在调查IMI患者的氧化/抗氧化状态，并将其结果与健康对照进行比较。本研究共纳入79例IMI患者(第一组)和90例健康个体(第二组)。我们使用Erel和Neşelioğlu的硫醇/二硫稳态测试。氧化/抗氧化平衡成分的集体和个体测量是通过这种新的硫醇/二硫稳态测试进行的。测定所有研究参与者血清抗氧化剂(总硫醇(toSH)、天然硫醇(SH))和氧化剂(二硫化物(SS))水平。对两组结果进行比较和统计分析。测定toSH、SH、SS水平后，分别分析各组患者SS/toSH%、SS/SH%水平，并进行统计学比较。两组间toSH、SH水平及SS/SH%、SS/toSH%比值差异有统计学意义(p)toSH:总硫醇;SH:天然硫醇;SS:二硫化;OS:氧化应激;ROS:活性氧;贴现:二氯荧光黄;MiOXSYS:男性不育氧化系统;MOSI:男性氧化应激不育症;LC:左卡尼汀;LAC: L-acetylcarnitine;维生素:维生素;燕麦:oligoasthenozoospermia;TMSC:活动精子总数;卫生组织:世界卫生组织;BMI:身体质量指数;DTNB: 5,5′-二硫代比斯-2-硝基苯甲酸;CV:变异系数;ROC:受者工作特性;PR:渐进的，NP:不渐进的。

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引用次数: 2

Antioxidant and anti-inflammatory protective effects of rutin and kolaviron against busulfan-induced testicular injuries in rats. 芦丁和可拉维铁对布苏芬致大鼠睾丸损伤的抗氧化和抗炎保护作用。

IF 2.4 4区医学 Q1 Medicine

Systems Biology in Reproductive Medicine

Pub Date : 2022-04-01 Epub Date: 2021-11-09 DOI: 10.1080/19396368.2021.1989727

Sunny O Abarikwu, Rex-Clovis C Njoku, Ifeoma G John, Benjamin A Amadi, Chidimma J Mgbudom-Okah, Chigozie L Onuah

There are few treatment options, including the use of natural phenolics-based combination therapy for mitigating male infertility conditions associated with chemotherapy. Busulfan is an anti-cancer drug that leads to testicular problems in humans. Here, we studied the effect of co-treatment of rutin and kolaviron against busulfan-induced testis damage. Young adult male Wistar rats were intraperitoneally injected busulfan (4 mg/kg b.w), and then orally administered rutin (30 mg/kg b.w), and kolaviron (50 mg/kg b.w) alone and combined for 60 days. Results revealed that rutin and kolaviron alone or in combination reversed busulfan-induced increase in oxidative stress along with sperm quality of treated animals. However, kolaviron and rutin separately improved the concentrations of MDA and GSH and sperm quality more than when they were combined. Similarly, rutin and kolaviron separately or in combination preserved spermatogenesis and relieved busulfan-induced increase in nitric oxide concentration, myeloperoxidase and 3β-hydroxysteroid dehydrogenase activities. Co-supplementation with kolaviron but not rutin nor when rutin was combined with kolaviron also improved the testicular level of tumor necrosis-alpha. Finally, the histological features in the testes caused by busulfan were reversed by rutin, whereas treatment with kolaviron alone or in combination with rutin partially protected the testis from busulfan-induced injury as demonstrated by the appearance of few germ cells, damaged tubules, loss of round spermatids and defoliation of the seminiferous epithelium. Thus, the combined treatment regimen of rutin and kolaviron sparingly prevented busulfan-induced testicular injuries in rats.Abbreviations: CAT: Catalase; GSH: Glutathione; 3β-HSD: 3β- hydroxysteroid Dehydrogenase; MDA: Malondialdehyde; TNF-α: Tumor necrosis-alpha; BUS: Busulfan; RUT: Rutin; KV: Kolaviron; TBARS: Thiobarbituric Acid Reactive Substances; MPO: Myeloperoxidase; ELISA: Enzyme-Linked Immunoassay; NAD: Nicotinamide Adenine Dinucleotide (oxidized); ROS: Reactive Oxygen Species.

很少有治疗选择，包括使用以天然酚类物质为基础的联合疗法来减轻与化疗相关的男性不育症。布苏凡是一种抗癌药物，会导致人类睾丸出现问题。本实验研究了芦丁与可拉维铁共处理对布苏芬致睾丸损伤的影响。研究方法:年轻成年雄性Wistar大鼠腹腔注射布硫凡(4 mg/kg b.w)，然后单独或联合口服芦丁(30 mg/kg b.w)和可拉维铁(50 mg/kg b.w)，持续60 d。结果表明，芦丁和可拉维铁单独或联合使用可逆转丁苏芬诱导的氧化应激增加以及治疗动物的精子质量。然而，科拉维铁和芦丁单独使用时，对MDA和GSH浓度的改善和精子质量的改善比它们合用时更大。同样，芦丁和可拉维铁单独或联合使用均可保存精子发生，并缓解布苏芬诱导的一氧化氮浓度、髓过氧化物酶和3β-羟基类固醇脱氢酶活性的升高。与克拉维铁联合补充而不补充芦丁或芦丁与克拉维铁联合补充也提高了睾丸肿瘤坏死α水平。最后，由丁磺芬引起的睾丸组织学特征被芦丁逆转，而单独使用可拉维铁或与芦丁联合使用可部分保护睾丸免受丁磺芬引起的损伤，表现为生殖细胞减少、小管受损、圆形精细胞丢失和精原上皮脱落。因此，芦丁与可拉维铁联合治疗方案对布苏芬所致大鼠睾丸损伤有一定的预防作用。缩写:CAT:过氧化氢酶;谷胱甘肽,谷胱甘肽;3β- hsd: 3β-羟基类固醇脱氢酶;MDA:丙二醛;TNF-α:肿瘤坏死α;总线:白消安;常规:芦丁;KV: Kolaviron;TBARS:硫代巴比妥酸反应物质;MPO:髓过氧物酶;ELISA:酶联免疫分析法;烟酰胺腺嘌呤二核苷酸(氧化);ROS:活性氧。

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引用次数: 11

Genistein affects gonadotrophin-releasing hormone secretion in GT1-7 cells via modulating kisspeptin receptor and key regulators. 染料木素通过调节kisspeptin受体和关键调节因子影响GT1-7细胞促性腺激素释放激素的分泌。

IF 2.4 4区医学 Q1 Medicine

Systems Biology in Reproductive Medicine

Pub Date : 2022-04-01 Epub Date: 2022-01-05 DOI: 10.1080/19396368.2021.2003910

Jingyuan Xiong, Ye Tian, Aru Ling, Zhenmi Liu, Li Zhao, Guo Cheng

Epidemiological studies have shown that genistein, an isoflavonoid phytoestrogen from soybean, affects endocrine and reproductive systems and alters pubertal onset. Administration of genistein in mice could impact the electrophysiology of hypothalamic neurons associated with the secretion of gonadotropin-releasing hormone (GnRH), a key component of hypothalamic-pituitary-gonadal (HPG) axis that governs hormone release and reproductive maturation. However, whether genistein could directly influence GnRH secretion in GnRH-specific neurons requires further investigation. Here, mouse hypothalamic GT1-7 neurons were recruited as a GnRH-expressing model to directly evaluate the effect and mechanisms of genistein on GnRH release. Results from this study demonstrated that genistein treatment decreased cell viability, impacted cell cycle distribution, and induced apoptosis of GT1-7 cells. A high concentration of genistein (20 μM) significantly increased GnRH secretion by 122.4% compared to the control. Since GnRH release is regulated by components of the kisspeptin-neurokinin-dynorphin (KNDy) system and regulators including SIRT1, PKC_γ, and MKRN3, their transcription and translation were examined. Significant increases were observed for the mRNA and protein levels of the KNDy component kisspeptin receptor (Gpr54/Kissr). Compared to the control, genistein treatment upregulated the level of Sirt1 mRNA level, while it downregulated Prkcg and Mkrn3 expression. Therefore, this study provided direct evidence that genistein treatment could affect GnRH secretion by modulating kisspeptin receptors, SIRT1, PKC_γ and MKRN3 in GT1-7 cells.Abbreviations: GnRH: gonadotropin-releasing hormone; HPG: hypothalamic-pituitary-gonadal; KNDy: kisspeptin-neurokinin-dynorphin; LH: luteinizing hormone; FSH: follicle-stimulating hormone; ARC: arcuate nucleus; ER: estrogen receptor; SIRT1: silent information regulator 1; PKCγ: protein kinase c γ: MKRN3: makorin ring finger protein 3; LC: lethal concentration; PI: propidium iodide; ECL: chemiluminescence; BCA: bicinchoninic acid assay; PBS: phosphate-buffered saline; CT: fluorescence reached threshold; PVDF: polyvinylidene difluoride.

流行病学研究表明，染料木素是一种来自大豆的异黄酮类植物雌激素，影响内分泌和生殖系统，并改变青春期的发生。给小鼠注射染料木素可以影响与促性腺激素释放激素(GnRH)分泌相关的下丘脑神经元的电生理，促性腺激素释放激素(GnRH)是下丘脑-垂体-性腺(HPG)轴的关键组成部分，控制激素释放和生殖成熟。但染料木素是否直接影响GnRH特异性神经元分泌GnRH还有待进一步研究。本研究招募小鼠下丘脑GT1-7神经元作为GnRH表达模型，直接评价染料木素对GnRH释放的影响及其机制。本研究结果表明染料木素处理降低了细胞活力，影响了细胞周期分布，诱导了GT1-7细胞凋亡。高浓度染料木素(20 μM)使GnRH分泌量较对照组显著增加122.4%。由于GnRH的释放受kisspeptin-neurokinin-dynorphin (KNDy)系统和包括SIRT1、PKCγ和MKRN3在内的调节因子的调控，因此研究了它们的转录和翻译。KNDy成分kisspeptin受体(Gpr54/Kissr)的mRNA和蛋白水平显著升高。与对照组相比，染料木素上调了Sirt1 mRNA水平，下调了Prkcg和Mkrn3的表达。因此，本研究提供了直接证据，表明染料木素治疗可以通过调节GT1-7细胞中的kisspeptin受体、SIRT1、PKCγ和MKRN3来影响GnRH的分泌。缩写:GnRH:促性腺激素释放激素;高压天然气:hypothalamic-pituitary-gonadal;KNDy: kisspeptin-neurokinin-dynorphin;LH:黄体生成素;促卵泡激素;ARC:弓状核;ER:雌激素受体;SIRT1:无声信息调节器1;PKCγ:蛋白激酶c γ; MKRN3: makorin无名指蛋白3;LC:致死浓度;PI:碘化丙啶;发射极耦合逻辑:化学发光;BCA:双醌酸测定法;PBS:磷酸盐缓冲盐水;CT:荧光达到阈值;PVDF:聚偏二氟乙烯。

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引用次数: 7

FSHR antagonists can trigger a PCOS-like state. FSHR拮抗剂可触发pcos样状态。

IF 2.4 4区医学 Q1 Medicine

Systems Biology in Reproductive Medicine

Pub Date : 2022-04-01 Epub Date: 2021-12-30 DOI: 10.1080/19396368.2021.2010837

Faiza Hanif Waghu, Karishma Desai, Sumana Srinivasan, Kaushiki S Prabhudesai, Vikas Dighe, Kareenhalli V Venkatesh, Susan Idicula-Thomas

Over the recent years, FSHR has become an important target for development of fertility regulating agents, as impairment of FSH-FSHR interaction can lead to subfertility or infertility. In our previous study, we identified a 9-mer peptide (FSHβ (89-97)) that exhibited FSHR antagonist activity. The histopathological and biochemical observations indicated, in addition to FSHR antagonism, a striking resemblance to a PCOS-like state. These observations led us to hypothesize that use of FSHR antagonists can trigger a PCOS-like state. In the present study, to validate this hypothesis, we performed qRT-PCR validation using ovarian tissue samples from our previous study. Expression of three genes known to be differentially expressed in PCOS was evaluated and found to be similar to the PCOS state. To further test the hypothesis, theoretical simulations were carried out by using the human menstrual cycle model available in the literature. Model simulations for FSHR antagonism were indicative of increased testosterone levels, increased ratio of luteinizing hormone/follicle stimulating hormone, and stockpiling of secondary follicles, which are typical characteristics of PCOS. The findings of this study will be relevant while reviewing the utility of FSHR antagonists for fertility regulation and reproductive medicine.Abbreviations: FSH: Follicle-stimulating hormone; FSHR: Follicle-stimulating hormone receptor; cAMP: Cyclic adenosine 3'5' monophosphate; PKA: Protein kinase A; PI3K: Phosphoinositide 3-kinase; PKB: protein kinase B; ERK1/2: Extracellular signal-regulated protein kinase 1/2; MAPK: Mitogen-activated protein kinases; T: testosterone; E2: estradiol; PCOS: Polycystic ovarian syndrome; LH: luteinizing hormone; Lhcgr: luteinizing hormone/choriogonadotropin receptor; CYP17A1: cytochrome P450 family 17 subfamily A member 1; Inhba: inhibin subunit beta A; qRT-PCR: Real-Time quantitative reverse transcription polymerase chain reaction; FSHβ: Follicle-stimulating hormone β subunit; Ct: Cycle threshold; Rn18s: Rattus norvegicus 18S ribosomal RNA.

近年来，FSH-FSHR相互作用受损可导致低生育能力或不孕症，因此FSH-FSHR已成为开发生育调节剂的重要靶点。在我们之前的研究中，我们发现了一种具有FSHR拮抗剂活性的9聚肽(FSHβ(89-97))。组织病理学和生化观察表明，除了FSHR拮抗剂外，与pcos样状态有惊人的相似之处。这些观察结果使我们假设使用FSHR拮抗剂可以触发pcos样状态。在本研究中，为了验证这一假设，我们使用我们之前研究中的卵巢组织样本进行了qRT-PCR验证。对PCOS中已知的三个差异表达基因的表达进行了评估，发现它们与PCOS状态相似。为了进一步验证这一假设，利用文献中可用的人类月经周期模型进行了理论模拟。FSHR拮抗剂的模型模拟表明，PCOS的典型特征是睾酮水平升高，促黄体生成素/促卵泡激素比例升高，次生卵泡堆积。本研究结果对FSHR拮抗剂在生育调控和生殖医学中的应用具有一定的参考价值。缩写:FSH:促卵泡激素;促卵泡激素受体;cAMP:环腺苷3'5'单磷酸;PKA:蛋白激酶A;PI3K:磷酸肌肽3-激酶;PKB:蛋白激酶B;ERK1/2:细胞外信号调节蛋白激酶1/2;MAPK:丝裂原活化蛋白激酶;T:睾酮;E2:雌二醇;PCOS:多囊卵巢综合征;LH:黄体生成素;Lhcgr:黄体生成素/绒毛膜促性腺激素受体;CYP17A1:细胞色素P450家族17亚家族A成员1;Inhba:抑制素亚单位β A;qRT-PCR:实时定量逆转录聚合酶链反应;FSHβ:促卵泡激素β亚基;Ct:周期阈值;Rn18s:褐家鼠18S核糖体RNA。

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引用次数: 3

Letrozole promotes the expression of integrin αvβ3 and HOXA10 in endometrium of endometriosis. 来曲唑促进子宫内膜异位症整合素αvβ3和HOXA10的表达。

IF 2.4 4区医学 Q1 Medicine

Systems Biology in Reproductive Medicine

Pub Date : 2022-04-01 Epub Date: 2021-12-28 DOI: 10.1080/19396368.2021.2013577

Jing Zhang, Lihui Wang, Chunyan Li, Hui Zhang, Rui Li, Mingjiang Li

Endometriosis is a common estrogen-dependent chronic inflammatory disease that leads to infertility in women of reproductive age. Perhaps infertility reflects the reduced expression of integrin αvβ3 and HOXA10 in endometriosis. Previous studies have shown that administration of letrozole, a non-steroidal aromatase inhibitor for cancer treatment, increased the clinical pregnancy rate in women with endometriosis, but the mechanisms remain to be determined. In this communication, a rat model of endometriosis was established. Animals were treated with letrozole at 2ug/kg of body weight, intragastric administration for 15 consecutive days. Letrozole increased the expression of αvβ3 and HOXA10 in the endometriosis model and endometrial receptivity.Abbreviations: WOI: window of implantation; RGD: Arg-Gly-Asp; HOX: homeobox; E2: estradiol; SPF: specific pathogen-free.

子宫内膜异位症是一种常见的雌激素依赖性慢性炎症性疾病，可导致育龄妇女不孕。不孕可能反映了子宫内膜异位症中整合素αvβ3和HOXA10的表达降低。先前的研究表明，使用来曲唑(一种非甾体芳香化酶抑制剂)治疗癌症可增加子宫内膜异位症患者的临床妊娠率，但其机制仍有待确定。本文建立了子宫内膜异位症大鼠模型。小鼠按2ug/kg体重给予来曲唑，连续灌胃15 d。来曲唑增加了αvβ3和HOXA10在子宫内膜异位症模型和子宫内膜容受性中的表达。WOI:植入窗口;RGD: Arg-Gly-Asp;HOX:同源框;E2:雌二醇;SPF:无特定病原体。

引用次数: 7