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The RNA-Binding Protein IGF2BP1 Marks Germ Cells but Is Dispensable for Mouse Fertility rna结合蛋白IGF2BP1标记生殖细胞,但对小鼠生育能力是必不可少的
IF 2.7 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-16 DOI: 10.1002/mrd.70016
Shu Wang, Shan Wu, Jinyan Tang, Yuan Chen, Yiyun Zhang, Wenwu Long, Xin Wu

Insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) is a key reader of N6-methyladenosine modifications that regulate target mRNA stability in eukaryotic cells; however, its role in germ cells has never been explored. Here, we analyzed the spatiotemporal expression of IGF2BP1 and revealed that it was present not only in oocytes of the mouse ovary but also in ZBTB16-positive undifferentiated spermatogonia in the mouse testis. Coimmunoprecipitation and fluorescence staining revealed that IGF2BP1 interacted with TRIM71, a regulator of spermatogonia differentiation, but that its expression was unaffected in the testes of Trim71 knockout mice. We also show that IGF2BP1 colocalized with components of the mRNA processing body (P-body), including DDX6 and EDC4. However, contrary to our expectations, using VASA (DDX4)-Cre-mediated conditional knockout mice, we found that germ cell-specific knockout of Igf2bp1 did not seem to affect the fertility of male or female mice. Further analysis revealed that spermatogenesis and ZBTB16-positive undifferentiated spermatogonia numbers in the testes of mutant mice remained unchanged and that there were no obvious changes in testicular morphology or cell subpopulations. In summary, although IGF2BP1 is preferentially expressed in germ cells, its function in germ cells may be dispensable.

胰岛素样生长因子2 mRNA结合蛋白1 (IGF2BP1)是真核细胞中n6 -甲基腺苷修饰调控靶mRNA稳定性的关键解读者;然而,它在生殖细胞中的作用从未被探索过。在此,我们分析了IGF2BP1的时空表达,发现它不仅存在于小鼠卵巢的卵母细胞中,也存在于小鼠睾丸的zbtb16阳性未分化精原细胞中。共免疫沉淀和荧光染色显示,IGF2BP1与精原细胞分化的调节因子TRIM71相互作用,但其在TRIM71敲除小鼠睾丸中的表达不受影响。我们还发现IGF2BP1与mRNA加工体(P-body)的组分共定位,包括DDX6和EDC4。然而,与我们的预期相反,使用VASA (DDX4)- cre介导的条件敲除小鼠,我们发现生殖细胞特异性敲除Igf2bp1似乎并不影响雄性或雌性小鼠的生育能力。进一步分析发现,突变小鼠睾丸中的精子发生和zbtb16阳性未分化精原细胞数量保持不变,睾丸形态和细胞亚群无明显变化。综上所述,尽管IGF2BP1优先在生殖细胞中表达,但其在生殖细胞中的功能可能是可有可无的。
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引用次数: 0
Unraveling the Clinical FSH Conundrum: Insights From the Small Ovarian Reserve Heifer Model 揭开临床 FSH 的谜团:小卵巢储备母牛模型的启示
IF 2.7 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-11 DOI: 10.1002/mrd.70007
James J. Ireland, Kaitlin R. Karl, Keith E. Latham

High doses of follicle stimulating hormone (FSH) are used during ovarian stimulation to maximize the number of oocytes recovered for in vitro fertilization (IVF) during assisted reproductive technology (ART) in women. Whether high FSH doses are detrimental to embryo viability remains controversial. Evidence from many clinical studies revealed that FSH dose is inversely correlated with live birth rate in women. The mechanistic basis for this effect has been elusive. This review summarizes over 20 years of work using a unique biomedical model, the small ovarian reserve heifer (SORH). Those studies revealed that excessive FSH doses can disrupt gene expression via multiple cell-signaling pathways in ovarian cells, resulting in follicular hyperstimulation dysgenesis (FHD). This compromises the capacity of ovulatory-size follicles to respond to gonadotropins, produce estradiol and ovulate, causes premature cumulus expansion and oocyte maturation, and impairs the fertilizability of oocytes. The SORH model has thus provided new insights into the nature and mechanisms of the deleterious effects of excessive FSH doses during ovarian stimulation. The SORH model has been and remains valuable for basic research and for the discovery of ways to optimize FSH dosing clinically to improve IVF success and ART outcomes.

在辅助生殖技术(ART)中,高剂量的促卵泡激素(FSH)用于卵巢刺激,以最大限度地恢复用于体外受精(IVF)的卵母细胞数量。高剂量卵泡刺激素是否对胚胎生存能力有害仍有争议。来自许多临床研究的证据表明,卵泡刺激素剂量与妇女活产率呈负相关。这种效应的机制基础一直难以捉摸。本文综述了20多年来使用一种独特的生物医学模型——小卵巢储备小母牛(SORH)的研究工作。这些研究表明,过量的FSH剂量可以通过卵巢细胞的多种细胞信号通路破坏基因表达,导致卵泡过度刺激发育不良(FHD)。这损害了排卵大小的卵泡对促性腺激素的反应、产生雌二醇和排卵的能力,导致卵丘过早膨胀和卵母细胞成熟,并损害卵母细胞的受精率。因此,SORH模型为卵巢刺激期间过量FSH有害影响的性质和机制提供了新的见解。SORH模型对于基础研究和发现临床优化FSH剂量以提高IVF成功率和ART结果的方法一直很有价值。
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引用次数: 0
Short-Term Bovine Ovarian Tissue Heterotopic Autotransplantation: VEGF Beneficial and Detrimental Effects 短期牛卵巢组织异位自体移植:VEGF的有益和有害影响
IF 2.7 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-09 DOI: 10.1002/mrd.70009
Ana N. P. Morais, Samara S. Souza, Francisco L. N. Aguiar, Gustavo D. A. Gastal, Fabiana A. S. Brandão, Juliany A. Souza, Lucy V. S. Ñaupas, Kele A. Alves, Benner G. Alves, Melba O. Gastal, Ana P. R. Rodrigues, José R. Figueiredo, Dárcio Í. A. Teixeira, Eduardo L. Gastal

Ovarian tissue transplantation (OTT) has been suggested as an alternative to preserving female fertility in livestock species, as currently performed in women. The OTT technique has been tested as xenografting or autografting in different body sites and animal species. Currently, there are no reports available regarding the autotransplantation of ovarian tissue using the bovine model and also testing the effect of vascular endothelial growth factor (VEGF) on graft survival. This study evaluated the effects of ovarian tissue short-term exposure to VEGF before heterotopic autotransplantation into a subcutaneous site (flank region) for 7 days in cattle. The initial finding was that after OTT and without pre-exposure to VEGF, the ovarian grafts had 42% of normal preantral follicles, which indicates a substantial step forward for this technique in cattle. Furthermore, VEGF exposure actively facilitated the process of neoangiogenesis, the proliferation capability of the stromal cells for activation of the cell cycle, maintained the balance between types I and III collagen fibers, and reduced the total collagen of the grafted tissue. Moreover, ovarian fragments previously exposed to VEGF tended to have greater follicular density; however, a detrimental effect of VEGF on follicular morphology was noticed. In conclusion, this study marks a significant step forward in bovine OTT and provides a foundation for further investigations into the specific pathways, stages, and durations of VEGF exposure to unveil strategies for refining ovarian transplantation techniques in cattle and other species.

卵巢组织移植(OTT)已被建议作为保留牲畜物种雌性生育能力的替代方法,目前在女性中进行。OTT技术已经在不同的身体部位和动物物种上进行了异种移植或自体移植的试验。目前,关于利用牛模型进行卵巢组织自体移植,以及检测血管内皮生长因子(VEGF)对移植物存活的影响,尚无报道。本研究评估了牛卵巢组织在异位自体皮下(侧腹区域)移植前7天短期暴露于VEGF的影响。最初的发现是,在OTT之后,没有预先暴露于VEGF,卵巢移植物有42%的正常腔前卵泡,这表明该技术在牛身上取得了实质性的进步。此外,VEGF暴露可积极促进新生血管生成过程,增强基质细胞的增殖能力,激活细胞周期,维持I型和III型胶原纤维的平衡,减少移植组织的总胶原蛋白。此外,先前暴露于VEGF的卵巢碎片往往具有更大的卵泡密度;然而,VEGF对卵泡形态有不利影响。总之,本研究标志着牛卵巢移植研究向前迈出了重要的一步,并为进一步研究VEGF暴露的具体途径、阶段和持续时间提供了基础,从而揭示了改进牛和其他物种卵巢移植技术的策略。
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引用次数: 0
Activation of Proteolysis During Oocyte In Vitro Maturation 卵母细胞体外成熟过程中蛋白水解的激活。
IF 2.7 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-28 DOI: 10.1002/mrd.70013
Filiz Tepekoy, Berk Bulut, Erdal Karaoz

In vitro maturation (IVM) is a form of assisted reproductive technology (ART) applied to obtain mature oocytes in culture. Decline in IVM success rates by age has led consideration of novel approaches based on cellular dynamics. Our aim was to achieve proteostasis in old bovine oocytes from 13 to 16-year-old bovine with a lower potential for fertilization. Lysosomal activation was achieved through increasing concentrations of proton pump activators PIP2 (0.1, 0.5, 1, and 5 μM), PMA (0.1, 1, 10, and 50 μM), and DOG (0.1, 1, 10, and 50 μM) at 6, 12, 18, and 24 h of IVM in old bovine oocytes. Morphological analysis was performed and IVM rates were determined. DQ-Red BSA was applied to live oocytes to determine proteolytic activation while lysosome density was determined by Lysotracker probe. Protein carbonylation was detected through oxyblot analysis. Polar body extrusion (PBE), through which a haploid nonfunctional polar body is released in the perivitelline space after completion of the first meiotic division, was observed in PIP2-0.1 μM, -0.5μM-6h; PIP2-5μM-12h; PMA-0.1μM-18h; PIP2-0.1μM, -0.5μM-24h groups. Oocyte diameter was the highest in DOG-1μM-6h, PMA-0.1μM-12h, PIP2-1μM-18h, and PIP2-0.5μM-24h groups. Morphological scores of oocytes were higher in young and old control groups. PIP2, PMA, and DOG affected oocyte quality positively after 6 h of IVM yielding in oocyte scores similar to the control group oocytes. However, they had a negative impact on the oocyte scores in longer periods of IVM, except for lower doses PMA (0.1 and 1 μM) at 12 h and PIP2 (0.5 μM) and PMA (0.1 μM) at 18 h, which were able to maintain the scores relatively closer to the control oocytes. Proteolytic activation was achieved in all groups at 6 h of culture. At all other time points PIP2 and PMA groups showed a better response to proteolytic activation. Lysosome density was increased in PIP2-5μM-6h; PIP2-0.1μM, -1μM-12h; PIP2-1μM, -5μM-18h as well as PMA-0.1μM-6h; PMA-1μM, -10μM-12h; PMA-1μM-18h; DOG-50μM-6h and DOG-0.1μM-12h. Protein carbonylation was the lowest in PIP2-0.1 μM groups at 12, 18, and 24 h. This study suggests that proton pump activators PIP2 and PMA was found to have a positive impact on IVM in terms of both morphological scores and proteolytic activation in a time and dose dependant manner.

体外成熟(IVM)是一种辅助生殖技术(ART),用于在培养中获得成熟的卵母细胞。IVM成功率随年龄的下降导致了基于细胞动力学的新方法的考虑。我们的目的是在13至16岁的牛的老牛卵母细胞中实现蛋白质静止,这些牛的受精潜力较低。通过增加质子泵激活剂PIP2(0.1、0.5、1和5 μM)、PMA(0.1、1、10和50 μM)和DOG(0.1、1、10和50 μM)的浓度,在老龄牛卵母细胞IVM的6、12、18和24 h实现溶酶体活化。形态学分析和IVM率测定。用DQ-Red BSA检测活卵母细胞的蛋白水解活性,用Lysotracker探针检测溶酶体密度。氧印迹法检测蛋白羰基化。在PIP2-0.1 μM, -0.5μM-6h观察到第一次减数分裂完成后单倍体无功能极体在卵泡周空间释放的极体挤压(Polar body extrusion, PBE);PIP2-5μM-12h;pma - 0.1μM-18h;PIP2-0.1μM, -0.5μM-24h组。狗-1μ m -6h、PMA-0.1μM-12h、PIP2-1μM-18h和PIP2-0.5μM-24h组卵母细胞直径最大。年轻对照组和老年对照组的卵母细胞形态学评分均较高。IVM产生6小时后,PIP2、PMA和DOG对卵母细胞质量有积极影响,其卵母细胞评分与对照组相似。然而,在较长时间的IVM中,它们对卵母细胞评分有负面影响,但12 h时低剂量的PMA(0.1和1 μM)以及18 h时低剂量的PIP2 (0.5 μM)和PMA (0.1 μM)能够保持相对接近对照卵母细胞的评分。在培养6 h时,所有组均实现蛋白水解活化。在所有其他时间点,PIP2和PMA组对蛋白水解激活表现出更好的反应。PIP2-5μM-6h时溶酶体密度增加;pip2 - 0.1μM, 1μM-12h;PIP2-1μM、-5μM-18h和PMA-0.1μM-6h;PMA-1μM, -10μM-12h;PMA-1μM-18h;DOG-50μM-6h和DOG-0.1μM-12h。在12、18和24 h时,PIP2-0.1 μM组蛋白羰基化最低。本研究表明,质子泵激活剂PIP2和PMA在形态学评分和蛋白水解激活方面对IVM有积极影响,且具有时间和剂量依赖性。
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引用次数: 0
Hormonal Regulation of Urokinase- and Tissue-Type Plasminogen Activator in Mouse Sertoli Cells 小鼠支持细胞尿激酶和组织型纤溶酶原激活物的激素调节。
IF 2.7 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-28 DOI: 10.1002/mrd.70012
Sara Carosi, Federica Innocenti, Lucia Monaco, Gaia Laurenzi, Rossana Saracino, Rita Canipari, Elena Vicini

A role for the plasminogen activator (PA) system has been postulated in mammalian gonads, considering the complex process of morphogenesis these organs undergo during their development. Our results show that mouse Sertoli cells under basal conditions produce both types of PA, tissue-type PA (tPA) and urokinase-type PA (uPA), and hormonal treatments increase the production of both enzymes. The increased enzyme secretion does not correlate with a parallel increase in their mRNAs. However, the proteolytic activity results from a balance between enzyme activity and inhibitors. Hormonal stimulation decreased the expression of the inhibitor PAI-1, suggesting that the increase in proteolytic activity might depend on the decreased production of PAI-1.

The expression of the two enzymes and their inhibitor depends on the seminiferous epithelium stage. We observed higher uPA mRNA levels at stages VII-VIII and IX-XII, tPA peaks at stages VII-VIII, and PAI-1 mRNA levels decreased at stages VII-VIII and IX-XII.

The testes from mice lacking the uPA gene (uPA−/−) presented statistically smaller sizes and weights. Histological analysis of uPA−/−animals showed tubular morphology defects and atypical residual bodies (RB), suggesting a defect in Sertoli cell phagocytosis. Moreover, we show lower sperm concentration and motility in uPA−/− mice. These data suggested an effective deficiency of testicular development in the absence of uPA.

考虑到哺乳动物性腺在发育过程中所经历的复杂的形态发生过程,纤溶酶原激活剂(PA)系统在哺乳动物性腺中起着一定的作用。我们的研究结果表明,小鼠支持细胞在基础条件下产生两种类型的PA,组织型PA (tPA)和尿激酶型PA (uPA),激素处理增加了这两种酶的产生。酶分泌的增加与mrna的平行增加并不相关。然而,蛋白水解活性源于酶活性和抑制剂之间的平衡。激素刺激降低了抑制剂PAI-1的表达,提示蛋白水解活性的增加可能依赖于PAI-1产生的减少。这两种酶及其抑制剂的表达取决于精原上皮的分期。我们观察到uPA mRNA水平在第7 - 8期和第9 - 12期升高,tPA在第7 - 8期达到峰值,PAI-1 mRNA水平在第7 - 8期和第9 - 12期下降。缺乏uPA基因(uPA-/-)的小鼠睾丸的尺寸和重量在统计学上较小。uPA-/-动物的组织学分析显示管状形态缺陷和非典型残体(RB),提示支持细胞吞噬功能缺陷。此外,我们发现uPA-/-小鼠的精子浓度和活力较低。这些数据表明,在缺乏uPA的情况下,睾丸发育明显不足。
{"title":"Hormonal Regulation of Urokinase- and Tissue-Type Plasminogen Activator in Mouse Sertoli Cells","authors":"Sara Carosi,&nbsp;Federica Innocenti,&nbsp;Lucia Monaco,&nbsp;Gaia Laurenzi,&nbsp;Rossana Saracino,&nbsp;Rita Canipari,&nbsp;Elena Vicini","doi":"10.1002/mrd.70012","DOIUrl":"10.1002/mrd.70012","url":null,"abstract":"<p>A role for the plasminogen activator (PA) system has been postulated in mammalian gonads, considering the complex process of morphogenesis these organs undergo during their development. Our results show that mouse Sertoli cells under basal conditions produce both types of PA, tissue-type PA (tPA) and urokinase-type PA (uPA), and hormonal treatments increase the production of both enzymes. The increased enzyme secretion does not correlate with a parallel increase in their mRNAs. However, the proteolytic activity results from a balance between enzyme activity and inhibitors. Hormonal stimulation decreased the expression of the inhibitor PAI-1, suggesting that the increase in proteolytic activity might depend on the decreased production of PAI-1.</p><p>The expression of the two enzymes and their inhibitor depends on the seminiferous epithelium stage. We observed higher <i>uPA</i> mRNA levels at stages VII-VIII and IX-XII, <i>tPA</i> peaks at stages VII-VIII, and <i>PAI-1</i> mRNA levels decreased at stages VII-VIII and IX-XII.</p><p>The testes from mice lacking the <i>uPA</i> gene (<i>uPA</i><sup>−/−</sup>) presented statistically smaller sizes and weights. Histological analysis of <i>uPA</i><sup>−/−</sup>animals showed tubular morphology defects and atypical residual bodies (RB), suggesting a defect in Sertoli cell phagocytosis. Moreover, we show lower sperm concentration and motility in <i>uPA</i><sup>−/−</sup> mice. These data suggested an effective deficiency of testicular development in the absence of uPA.</p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reproductive Physiology and Molecular Mechanisms Underlying Testicular Development and Spermatogenesis in Echinoderms: A Marine Invertebrate Deuterostomes 棘皮动物睾丸发育和精子发生的生殖生理学和分子机制:一种海洋无脊椎后口动物。
IF 2.7 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-20 DOI: 10.1002/mrd.70011
Ziming Li, Yujia Yang

Echinoderms exhibit a wide range of reproductive strategies as adaptations to variable environments. The processes of gonadal development, germ cell differentiation, and spermatogenesis in echinoderms are crucial physiological processes that warrant further in-depth exploration. This review systematically summarizes research from early basic sciences to recent studies on male gonadal development and spermatogenesis, encompassing morphology, histology, physiology, cell biology, developmental biology, and evolutionary biology. We introduce the structural and cellular similarities and differences among model or non-model organisms from five classes of echinoderms to provide insights for future comparative research between higher vertebrates and lower organisms. The regulatory systems involved in echinoderm spermatogenesis are described from various aspects including nutritional supply, environmental factors, neurological influences, endocrinological influences, and hormonal influences. This article aims to elucidate gonadal development and spermatogenesis in echinoderms—organisms at unique evolutionary nodes—providing valuable materials for studying adaptive evolution and developmental biology. Additionally, a comprehensive summary of characterized genes and gene markers associated with testes development and spermatogenesis is provided as useful information for future systematic studies on cell subpopulations. Future studies can focus on molecular changes associated with chromatin remodeling during germ cell development, cellular differentiation, and intercellular communication mediated by receptor-ligand interactions, to further our understanding of biological processes and regulatory networks involved in echinoderm gonadal development and spermatogenesis.

棘皮动物表现出广泛的生殖策略,以适应多变的环境。棘皮动物的性腺发育、生殖细胞分化和精子发生过程是重要的生理过程,值得进一步深入研究。本文系统地综述了从早期的基础科学到最近的男性性腺发育和精子发生的研究,包括形态学、组织学、生理学、细胞生物学、发育生物学和进化生物学。本文介绍了五类棘皮动物的模式生物和非模式生物在结构和细胞上的异同,为今后高等脊椎动物和低等生物的比较研究提供参考。从营养供应、环境因素、神经影响、内分泌影响和激素影响等方面阐述了棘皮动物精子发生的调控系统。本文旨在阐明棘皮动物这种处于独特进化节点的生物的性腺发育和精子发生,为研究适应进化和发育生物学提供有价值的材料。此外,全面总结了与睾丸发育和精子发生相关的特征基因和基因标记,为未来对细胞亚群的系统研究提供了有用的信息。未来的研究可以关注生殖细胞发育、细胞分化和受体-配体相互作用介导的细胞间通讯过程中染色质重塑相关的分子变化,以进一步了解包皮动物性腺发育和精子发生的生物学过程和调控网络。
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引用次数: 0
Putting Nose into Reproduction: Influence of Nasal and Reproductive Odourant Signaling on Male Reproduction 让鼻子进入生殖:鼻腔和生殖气味信号对男性生殖的影响。
IF 2.7 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-20 DOI: 10.1002/mrd.70010
Kamaraj Elango, Jukka Kekäläinen

Odourant receptors (ORs) are not restricted only to the nose, but also occur in many other organs and tissues, including the reproductive system. In fact, ORs are the most heavily expressed in testis than in any other extra-nasal tissue. Accumulating evidence suggests that olfactory and reproductive systems are both structurally and functionally linked and that these interconnections can influence various aspects of reproduction. In this article, we first review our current understanding of these interconnections and then collate accumulated evidence on the presence of ORs in the male reproductive system and sperm cells. We then investigate the potential role of female reproductive tract odourants in sperm chemotaxis and selection. Finally, since the existing evidence especially for sperm odor sensing capability and its physiological function are controversial, we also review potential reasons for the controversy and propose some ways to resolve the debate. Collectively, we conclude that reproductive odourant signaling may play an important, although currently largely unclear role in many key processes directly related to male fertility. However, since we lack holistic understanding of the functional significance of ORs and odor sensing pathways of the male reproductive system, more empirical research is warranted.

气味受体(ORs)不仅局限于鼻子,也存在于许多其他器官和组织中,包括生殖系统。事实上,与其他任何鼻外组织相比,睾丸中的ORs表达最多。越来越多的证据表明,嗅觉和生殖系统在结构和功能上都是相互联系的,这些相互联系可以影响生殖的各个方面。在本文中,我们首先回顾了我们目前对这些相互关系的理解,然后整理了男性生殖系统和精子细胞中存在ORs的积累证据。然后,我们研究了女性生殖道气味剂在精子趋化和选择中的潜在作用。最后,由于现有的证据,特别是关于精子气味感知能力及其生理功能的证据存在争议,我们也回顾了争议的可能原因,并提出了一些解决争议的方法。总的来说,我们得出结论,生殖气味信号可能在许多与男性生育直接相关的关键过程中发挥重要作用,尽管目前还不清楚。然而,由于我们缺乏对男性生殖系统的ORs和气味感知途径的功能意义的整体理解,需要更多的实证研究。
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引用次数: 0
Gentamicin Has No Significant Adverse Effect on Porcine Embryo Development In Vitro 庆大霉素对猪胚胎体外发育无明显不良影响
IF 2.7 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-29 DOI: 10.1002/mrd.70008
Rylie S. Noland, Bethany K. Redel, Marissa G. LaMartina, Paula R. Chen, Randall S. Prather

The composition of the culture medium affects the viability and developmental competency of porcine embryos produced in vitro. Previous transcriptional profiling has identified areas of improvement in the formulation of these media. Xenobiotic metabolism-related genes were upregulated in in vitro-cultured porcine embryos compared to their in vivo-derived counterparts, and the antibiotic gentamicin is a component of porcine embryo culture media. While effective against a broad spectrum of bacteria, gentamicin has been observed to be toxic to rat embryos and may induce changes in gene expression in cell culture. The objective of this study was to determine if gentamicin has an adverse effect on the development of porcine embryos. After in vitro fertilization, presumptive zygotes were placed in either MU4 medium containing gentamicin or MU4 medium without gentamicin. No difference was detected in blastocyst development, total cell number, apoptotic index, or expression of 3 selected genes between embryos cultured with or without gentamicin (p > 0.05). Therefore, porcine embryos are able to tolerate the presence of 10 μg/mL gentamicin without significant impacts on blastocyst development rate, total cell number, or apoptosis.

培养基的组成影响体外培养的猪胚胎的生存能力和发育能力。以前的转录分析已经确定了这些介质的配制方面有待改进的领域。体外培养的猪胚胎与体内培养的猪胚胎相比,外源代谢相关基因表达上调,抗生素庆大霉素是猪胚胎培养基的一种成分。虽然对广泛的细菌有效,但庆大霉素已被观察到对大鼠胚胎有毒,并可能诱导细胞培养中基因表达的变化。本研究的目的是确定庆大霉素是否对猪胚胎的发育有不利影响。体外受精后,假定受精卵被放置在含有庆大霉素的MU4培养基或不含庆大霉素的MU4培养基中。加庆大霉素与不加庆大霉素培养的胚胎囊胚发育、细胞总数、凋亡指数及3个选定基因的表达均无差异(p > 0.05)。因此,猪胚胎能够耐受10 μg/mL庆大霉素的存在,而不会对囊胚发育率、细胞总数或凋亡产生显著影响。
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引用次数: 0
CABS1 Is Essential for Progressive Motility and the Integrity of Fibrous Sheath in Mouse Epididymal Spermatozoa CABS1 对小鼠附睾精子的进行性运动和纤维鞘的完整性至关重要
IF 2.7 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-11 DOI: 10.1002/mrd.23776
Xiuling Zhao, Wenwen Zhou, Junyu Nie, Xiaoning Zhang, Xuhui Zeng, Xiaoli Sun

The calcium-binding protein spermatid-associated 1 (CABS1) localizes to the principal piece of mature sperm flagella. Deletion of CABS1 results in subfertility in male mice, possibly due to an impaired annulus in the sperm flagella. However, it is unknown whether there are other mechanisms by which CABS1 affects male fertility. Our current investigation has uncovered that CABS1 is located in the midsection of the flagellum in testicular sperm and the principal piece in epididymal sperm. Moreover, male mice lacking CABS1 exhibit a defect in the progressive motility of sperm. Furthermore, the regulation of calcium levels, which has been reported to have a significant impact on sperm motility, capacitation, and the acrosome reaction, is also affected when sperm are exposed to alkalized high-salt buffer (pH 8.0) and progesterone (100 μM) in Cabs1-null spermatozoa. This alteration in calcium response may contribute to changes in the phosphorylation of PKA substrates and subsequent phosphorylation of tyrosine residues. Additionally, the absence of CABS1 leads to a defective fibrous sheath and abnormal configuration of doublet microtubules in post-testicular sperm. These findings indicate that the absence of CABS1 also disrupts the structural integrity of the fibrous sheath, resulting in male subfertility. The highly conserved nature of CABS1 in humans suggests that it could potentially be a contributing factor to asthenozoospermia in men.

钙结合蛋白精子相关1(CABS1)定位于成熟精子鞭毛的主要部分。缺失 CABS1 会导致雄性小鼠不育,这可能是由于精子鞭毛的环状结构受损所致。然而,CABS1 是否还有其他影响雄性生育能力的机制尚不清楚。我们目前的研究发现,CABS1 位于睾丸精子鞭毛的中段和附睾精子鞭毛的主要部分。此外,缺乏 CABS1 的雄性小鼠表现出精子逐渐运动的缺陷。此外,据报道,钙水平的调节对精子的运动能力、获能能力和顶体反应有重大影响,而当Cabs1无效精子暴露于碱性高盐缓冲液(pH 8.0)和黄体酮(100 μM)中时,钙水平的调节也会受到影响。钙反应的这种改变可能会导致 PKA 底物的磷酸化和随后的酪氨酸残基磷酸化发生变化。此外,CABS1 的缺失导致睾丸后精子的纤维鞘缺陷和双微管配置异常。这些发现表明,CABS1 的缺失也会破坏纤维鞘的结构完整性,导致男性不育。CABS1在人类中的高度保守性表明,它可能是导致男性无精子症的一个潜在因素。
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引用次数: 0
Early Cell Lineage Formation in Mammals: Complexity, Species Diversity, and Susceptibility to Disruptions Impacting Embryo Viability 哺乳动物的早期细胞系形成:复杂性、物种多样性以及对影响胚胎活力的干扰的易感性。
IF 2.7 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-27 DOI: 10.1002/mrd.70002
Keith E. Latham

The emergence of the earliest cell lineages in mammalian embryos is a complex process that utilizes an extensive network of chromatin regulators, transcription factors, cell polarity regulators, and cellular signaling pathways. These factors and pathways operate over a protracted period of time as embryos cleave, undergo compaction, and form blastocysts. The first cell fate specification event separates the pluripotent inner cell mass from the trophectoderm lineage. The second event separates pluripotent epiblast from hypoblast. This review summarizes over 50 years of study of these early lineage forming events, addressing the complexity of the network of interacting molecules, cellular functions and pathways that drive them, interspecies differences, and aspects of these mechanisms that likely underlie their high susceptibility to disruption by numerous environmental factors that can compromise embryo viability, such as maternal health and diet, environmental toxins, and other stressors.

哺乳动物胚胎中最早细胞系的出现是一个复杂的过程,需要利用染色质调节因子、转录因子、细胞极性调节因子和细胞信号通路组成的广泛网络。在胚胎裂解、压实和形成囊胚的过程中,这些因子和通路会在很长一段时间内发挥作用。第一个细胞命运分化事件将多能内细胞团与滋养层细胞系分开。第二个过程将多能的上胚层与下胚层分离。本综述总结了 50 多年来对这些早期细胞系形成事件的研究,探讨了相互作用分子网络的复杂性、驱动这些事件的细胞功能和途径、种间差异,以及这些机制中可能导致它们极易被众多环境因素(如母体健康和饮食、环境毒素和其他压力因素)破坏的方面。
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Molecular Reproduction and Development
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