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Lipid Enriched Reduced Nutrient Culture Medium Improves Bovine Blastocyst Formation. 富脂减量培养基促进牛囊胚形成。
Pub Date : 2023-11-01 DOI: 10.1530/RAF-23-0057
Rolando Pasquariello, Mingxiang Zhang, Jason R Herrick, Alison Ermisch, John Becker, William B Schoolcraft, Jennifer P Barfield, Ye Yuan, Rebecca L Krisher

The refinement of embryo culture media is essential in improving embryo viability and in vitro production efficiency. Our previous work demonstrated that the nutrients (carbohydrates, amino acids, and vitamins) in traditional culture media far exceed the need for an embryo and producing developmentally competent embryos in a reduced nutrient environment is feasible. Here, we aim to evaluate the impact of exogenous lipid and L-carnitine supplementation on bovine blastocyst development and refine our RN condition further. Zygotes were cultured in the control medium (100% nutrients) and reduced nutrient media containing 6.25% of the standard nutrient concentrations supplemented with L-carnitine and lipid free or lipid rich BSA. Increased blastocyst development was observed in the reduced nutrient lipid rich medium compared to the other two groups. However, in both reduced nutrient conditions, blastocyst cell numbers were lower than those obtained in the control condition. We then examined the expression level of 18 transcripts correlated with lipid metabolism, glucose metabolism, redox balance, and embryo quality, along with mitochondrial DNA copy numbers, ATP productions, and lipid profile. The results indicated lipid metabolism, embryo quality, and redox enzyme related genes were upregulated while glucose related gene was downregulated in embryos derived from reduced nutrient lipid rich condition Finally, we identified that the lipid rich BSA has enriched linoleic, stearic, oleic, palmitic, and alpha-linoleic fatty acids, a lipid profile that may contribute to the increased lipid metabolism and improved blastocyst development of the bovine embryos under the reduced nutrient condition.

胚胎培养基的改良是提高胚胎存活率和体外生产效率的关键。我们之前的工作表明,传统培养基中的营养物质(碳水化合物、氨基酸和维生素)远远超过胚胎的需要,在营养减少的环境中产生发育能力强的胚胎是可行的。在这里,我们的目的是评估外源性脂质和左旋肉碱补充对牛囊胚发育的影响,并进一步完善我们的RN条件。受精卵分别在对照培养基(100%营养物)和含有6.25%标准营养物浓度的还原培养基中培养,培养基中添加左旋肉碱和无脂或富脂牛血清蛋白。与其他两组相比,在减少营养脂质的培养基中观察到囊胚发育增加。然而,在两种低营养条件下,囊胚细胞数量均低于对照组。然后,我们检测了与脂质代谢、葡萄糖代谢、氧化还原平衡、胚胎质量、线粒体DNA拷贝数、ATP产生和脂质谱相关的18个转录本的表达水平。结果表明,在营养脂质减少的条件下,胚胎的脂质代谢、胚胎质量和氧化还原酶相关基因上调,而葡萄糖相关基因下调。最后,我们发现富脂BSA富含亚油酸、硬脂酸、油酸、棕榈酸和α -亚油酸脂肪酸。在低营养条件下,脂质谱可能有助于提高牛胚胎的脂质代谢和改善囊胚发育。
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引用次数: 0
"A glimmer of hope" - Perceptions, barriers, and drivers for medicinal cannabis use amongst Australian and New Zealand people with endometriosis. “一线希望”——澳大利亚和新西兰子宫内膜异位症患者对药用大麻使用的看法、障碍和驱动因素。
Pub Date : 2023-10-01 DOI: 10.1530/RAF-23-0049
Justin Sinclair, Jason Abbott, Antonina Mikocka-Walus, Cecilia H M Ng, Jerome Sarris, Subhadra Evans, Mike Armour

Previous quantitative research has shown that cannabis use, mostly illicit, is used for symptom management amongst those with endometriosis living in Australia or New Zealand, but the drivers and barriers for use of legal, medicinal cannabis in this population are currently unclear. This study sought to investigate, via online focus-groups, the perceptions, barriers, drivers, and experiences associated with cannabis use, whether legal or illicit, amongst 37 Australians and New Zealanders, aged 18-55, with a medical diagnosis of endometriosis. Previous cannabis usage was not required to participate. Discussion topics included strategies employed to manage symptoms, exploration of current medications, previous use of cannabis for pain management, and interest in using medicinal cannabis as a management strategy. Participants with moderate to severe symptoms of medically diagnosed endometriosis reported inadequacies with their current medical and self-management strategies and were inclined to try medicinal cannabis, both as part of their medical management and as part of a clinical trial. Barriers to medicinal cannabis adoption identified in this cohort included high costs of legal cannabis products, lack of clarity and fairness in current roadside drug testing laws and workplace drug testing policies, concern over the impact of stigma affecting familial, social and workplace life domains, and subsequent judgement and the lack of education/engagement from their medical providers regarding cannabis use. Given the interest in medicinal cannabis and the reported lack of effective symptom management, clinical trials are urgently required to determine the potential role that medicinal cannabis may play in reducing the symptoms of endometriosis.

先前的定量研究表明,在澳大利亚或新西兰的子宫内膜异位症患者中,大麻的使用主要是非法的,用于症状管理,但目前尚不清楚在这一人群中使用合法药用大麻的驱动因素和障碍。这项研究试图通过在线焦点小组,调查37名年龄在18-55岁、经医学诊断为子宫内膜异位症的澳大利亚人和新西兰人对大麻使用的看法、障碍、驱动因素和经历,无论是合法还是非法。以前吸食大麻的人不需要参加。讨论主题包括用于管理症状的策略、对当前药物的探索、以前使用大麻进行疼痛管理以及对使用药用大麻作为管理策略的兴趣。患有中度至重度医学诊断子宫内膜异位症症状的参与者报告称,他们目前的医疗和自我管理策略存在不足,并倾向于尝试药用大麻,这既是他们医疗管理的一部分,也是临床试验的一部分。这一群体中发现的药用大麻采用障碍包括合法大麻产品成本高、现行路边毒品检测法和工作场所毒品检测政策缺乏明确性和公平性、对污名化影响家庭、社会和工作场所生活领域的影响的担忧、,以及随后的判断以及医疗服务提供者对大麻使用缺乏教育/参与。鉴于人们对药用大麻的兴趣以及据报道缺乏有效的症状管理,迫切需要进行临床试验,以确定药用大麻在减轻子宫内膜异位症症状方面可能发挥的潜在作用。
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引用次数: 0
Reproduction in life and death: should cancer patients with a poor prognosis be offered fertility preservation interventions? 生与死中的生殖:是否应为预后不良的癌症患者提供生育保护干预措施?
Pub Date : 2023-09-01 DOI: 10.1530/RAF-23-0047
Georgina L Jones, Anne-Mariead Folan, Bob Phillips, Richard A Anderson, Jonathan Ives

In the context of a cancer diagnosis, fertility preservation interventions are used to mitigate the potential impact of gonadotoxic cancer treatment upon fertility. They provide patients with cancer the option to freeze their reproductive material to have their own biological child following treatment. The evidence suggests some clinicians are less likely to have fertility preservation discussions with patients who have an aggressive or metastatic cancer which has a poor prognosis. Although this is contrary to current policy recommendations, there is a lack of guidance relating to offering fertility preservation in the context of a poor prognosis to support clinicians. Controversy surrounds posthumous reproduction, and whether the wishes of the cancer patient, when living and deceased should take precedence over others' wellbeing. We consider the question of whether cancer patients with a poor prognosis should be offered FP from an ethics perspective. We structure the paper around key arguments to which multiple ethical principles might pertain, first establishing a central argument in favour of offering fertility preservation based on respect for autonomy, before exploring counterarguments. We conclude by proposing that a defeasible assumption should be adopted in favour of offering fertility preservation to all cancer patients who might benefit from it. It is important to recognise that patients could benefit from fertility preservation in many ways, and these are not limited to having a parenting experience. The burden of proof rests on the clinician in collaboration with their multi-disciplinary team, to show that there are good grounds for withholding the offer.

在癌症诊断的背景下,使用保持生育能力干预措施来减轻性腺毒性癌症治疗对生育能力的潜在影响。他们为癌症患者提供了冷冻生殖材料的选择,以便在治疗后拥有自己的亲生子女。证据表明,一些临床医生不太可能与患有侵袭性或转移性癌症且预后不良的患者进行生育保留讨论。尽管这与目前的政策建议相反,但缺乏在预后不佳的情况下提供生育保护以支持临床医生的指导。争议围绕着死后生殖,以及癌症患者在活着和去世时的意愿是否应该优先于他人的福祉。我们从伦理学的角度考虑是否应为预后不良的癌症患者提供FP的问题。我们围绕多种伦理原则可能涉及的关键论点构建了这篇论文,首先建立了一个支持在尊重自主权的基础上提供生育保护的核心论点,然后再探讨反驳论点。最后,我们建议采用一种不可行的假设,为所有可能从中受益的癌症患者提供生育保护。重要的是要认识到,患者可以在许多方面从生育保护中受益,而这些并不局限于有养育经验。举证责任在于临床医生与他们的多学科团队合作,以表明有充分的理由拒绝报价。
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引用次数: 0
COVID-19 vaccine and its effect on sperm. 新冠肺炎疫苗及其对精子的影响。
Pub Date : 2023-01-25 Print Date: 2023-01-01 DOI: 10.1530/RAF-22-0098
Rujittika Mungmunpuntipantip, Viroj Wiwanitkit
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引用次数: 0
Matrix metalloproteinase-induced cervical extracellular matrix remodelling in pregnancy and cervical cancer. 妊娠和宫颈癌症中基质金属蛋白酶诱导的宫颈细胞外基质重塑。
Pub Date : 2022-08-09 Print Date: 2022-07-01 DOI: 10.1530/RAF-22-0015
Emmanuel Amabebe, Henry Ogidi, Dilly O Anumba

Abstract: The phenomenal extracellular matrix (ECM) remodelling of the cervix that precedes the myometrial contraction of labour at term or preterm appears to share some common mechanisms with the occurrence, growth, invasion and metastasis of cervical carcinoma. Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are pivotal to the complex extracellular tissue modulation that includes degradation, remodelling and exchange of ECM components, which contribute to homeostasis under normal physiological conditions such as cervical remodelling during pregnancy and puerperium. However, in cancer such as that of the uterine cervix, this extensive network of extracellular tissue modulation is altered leading to disrupted cell-cell and cell-basement membrane adhesion, abnormal tissue growth, neovascularization and metastasis that disrupt homeostasis. Cervical ECM remodelling during pregnancy and puerperium could be a physiological albeit benign neoplasm. In this review, we examined the pathophysiologic differences and similarities in the role of MMPs in cervical remodelling and cervical carcinoma.

Lay summary: During pregnancy and childbirth, the cervix, which is the barrel-shaped lower portion of the womb that connects to the vagina, gradually softens, shortens and opens to allow birth of the baby. This process requires structural and biochemical changes in the cervix that are stimulated by enzymes known as matrix metalloproteinases. Interestingly, these enzymes also affect the structural and biochemical framework of the cervix during cervical cancer, although cervical cancers usually occur after infection by human papillomavirus. This review is intended to identify and explain the similarities and differences between the structural and chemical changes in the cervix during pregnancy and childbirth and the changes seen in cervical cancer.

图形摘要:摘要:在足月或早产分娩的子宫肌层收缩之前,子宫颈的显著细胞外基质(ECM)重塑似乎与宫颈癌的发生、生长、侵袭和转移有一些共同的机制。基质金属蛋白酶(MMPs)是锌依赖性内肽酶,对复杂的细胞外组织调节至关重要,包括ECM成分的降解、重塑和交换,在正常生理条件下,如妊娠和产褥期的宫颈重塑,有助于体内平衡。然而,在癌症(如子宫颈癌)中,这种广泛的细胞外组织调节网络发生改变,导致细胞-细胞和细胞基底膜粘附破坏、组织生长异常、新生血管形成和转移,破坏体内平衡。妊娠期和产褥期子宫颈ECM重塑可能是一种生理性的良性肿瘤。在这篇综述中,我们研究了MMPs在宫颈重塑和宫颈癌中作用的病理生理学差异和相似性。概述:在怀孕和分娩期间,子宫颈是子宫的筒状下部,与阴道相连,它会逐渐软化、缩短和打开,以允许婴儿出生。这一过程需要子宫颈在基质金属蛋白酶的刺激下发生结构和生化变化。有趣的是,尽管宫颈癌通常发生在人乳头瘤病毒感染后,但在癌症期间,这些酶也会影响宫颈的结构和生化框架。本综述旨在确定和解释妊娠和分娩期间宫颈的结构和化学变化与癌症宫颈变化之间的相似性和差异性。
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引用次数: 0
Endometriosis in transmasculine individuals. 变性人子宫内膜异位症。
Pub Date : 2022-04-20 eCollection Date: 2022-04-01 DOI: 10.1530/RAF-21-0096
Cecile A Ferrando

Transmasculine people are assigned female at birth but identify as male. These patients often are prescribed testosterone therapy as part of their transition. This treatment can affect ovulation and stop menstrual periods. Endometriosis is a common condition that causes pelvic pain in some people born with female pelvic organs. Not a lot is known about transmasculine people and how often endometriosis affects them. Testosterone should help treat if not reduce the incidence of endometriosis. This commentary looks at the current literature in order to help clarify existing knowledge gaps. Transmasculine patients who present for hysterectomy as a surgery to help them affirm themselves in their self-identified gender sometimes report pelvic pain symptoms as well. There are many reasons why patients report pain before surgery, and this can be related to endometriosis, even though this diagnosis is less expected in this group. Providers caring for transmasculine patients should be aware of this.

变性人在出生时被指定为女性,但被认定为男性。这些患者通常会接受睾酮治疗,作为其过渡期的一部分。这种治疗可以影响排卵并停止月经。子宫内膜异位症是一种常见的疾病,会导致一些天生具有女性盆腔器官的人出现盆腔疼痛。关于变性人以及子宫内膜异位症对他们的影响,我们知之甚少。如果不能降低子宫内膜异位症的发生率,睾酮应该有助于治疗。这篇评论着眼于当前的文献,以帮助澄清现有的知识差距。将子宫切除术作为一种手术来帮助他们确认自己的性别的变性患者有时也会报告骨盆疼痛症状。患者在手术前报告疼痛的原因有很多,这可能与子宫内膜异位症有关,尽管这种诊断在这一群体中不太常见。照顾变性患者的提供者应该意识到这一点。
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引用次数: 3
Did the NICE guideline for progesterone treatment of threatened miscarriage get it right? NICE关于黄体酮治疗先兆流产的指南正确吗?
Pub Date : 2022-04-07 eCollection Date: 2022-04-01 DOI: 10.1530/RAF-21-0122
W Colin Duncan

In November 2021, NICE updated its clinical guideline that covers the management of threatened miscarriage in the first trimester. They recommended offering vaginal micronised progesterone twice daily until 16 completed weeks of pregnancy in those with a previous miscarriage. However, the duration of treatment is not evidence based. In the major clinical trial that informed the guideline, there was no benefit in starting progesterone after 9 weeks and the full effect of progesterone was present at 12 weeks of pregnancy. There are theoretical risks impacting offspring health in later life after maternal pharmaceutical progesterone treatment. As the effect of progesterone seems to be complete by 12 weeks of gestation, we should consider carefully whether to follow the guidance and treat up to 16 weeks of pregnancy.

Lay summary: In November 2021, new guidelines were published about the management of bleeding in early pregnancy. If someone who has had a previous miscarriage starts bleeding, they should now be treated with progesterone as this slightly reduces the chance of miscarriage. The guideline says progesterone should be given if the pregnancy is in the womb, and potentially normal, until 16 weeks of pregnancy. However, in the big studies looking at progesterone's effect in reducing miscarriage the beneficial effects of progesterone were complete by 12 weeks of pregnancy. At that stage, it is the placenta and not the mother's ovary that makes the progesterone to support the pregnancy. We do not know the long-term effects of giving extra progesterone during pregnancy on the offspring. Some research has raised the possibility that there might be some adverse effects if progesterone is given for too long. Maybe the guidance should have suggested stopping at 12 weeks rather than 16 weeks of pregnancy.

2021年11月,NICE更新了其临床指南,涵盖了妊娠早期先兆流产的管理。他们建议,对于有过流产经历的患者,每天两次提供阴道微粉化孕酮,直到妊娠16周。然而,治疗的持续时间没有证据依据。在指导该指南的主要临床试验中,9周后开始使用黄体酮没有任何益处,并且在怀孕12周时出现了黄体酮的全部效果。母体药物黄体酮治疗后,理论上存在影响后代健康的风险。由于黄体酮的作用似乎在妊娠12周时完成,我们应该仔细考虑是否遵循指导并治疗妊娠16周。概要:2021年11月,关于妊娠早期出血管理的新指南发布。如果以前流产过的人开始出血,现在应该用黄体酮治疗,因为这会稍微降低流产的几率。该指南称,如果妊娠在子宫内,并且可能正常,则应给予孕酮,直到妊娠16周。然而,在研究黄体酮减少流产效果的大型研究中,黄体酮的有益效果在怀孕12周时完成。在那个阶段,是胎盘而不是母亲的卵巢产生了支持怀孕的孕酮。我们不知道在怀孕期间给予额外孕酮对后代的长期影响。一些研究提出,如果长期服用黄体酮,可能会产生一些不良反应。也许指南应该建议在怀孕12周时停止,而不是16周。
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引用次数: 0
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Reproduction & fertility
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