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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。
Q2 REPRODUCTIVE BIOLOGY 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。
Q2 REPRODUCTIVE BIOLOGY 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?
Q2 REPRODUCTIVE BIOLOGY 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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