Ultrastructural characterization of whole hydrosalpinx from infertile Chinese women

Hydrosalpinx (HSP) has been shown to be detrimental to the outcome of assisted reproduction, but little is known of its pathology. This prospective study examined and detailed ultrastructural characterization of HSP of infertile women presenting for assisted reproductive treatments. Both light and electron microscopies were used to characterize HSP. Hematoxylin and eosin staining of HSP showed areas without epithelial cell lining or with abnormalities such as flattening of the epithelial layer and exfoliation of epithelial cells with occasional normal columnar epithelial lining. HSP muscle fibers were atrophic and occasionally replaced by fibrous tissues, or separated by areas of severe edema. Inflammatory cells could be found in hydrosalpinx fluid (HF) in the lumen in areas with flattened to no epithelial cells, without epithelial lining, as well as in dilated blood vessels and/or lymph vessels. Scanning electron microscopy of the epithelial surface revealed epithelial denudation-severe loss of both cilia and microvilli and stomata exuding globular bodies on eroded ampulla surfaces. Severe chronic inflammation and damage to the epithelial lining and musculature of Fallopian tubes and the presence of inflammatory cells provides an explanation for HF formation, and thus for the detrimental effects of HF on reproductive processes and IVF outcome.     

A hierarchical Bayesian approach to modeling embryo implantation following in vitro fertilization

In vitro fertilization and embryo transfer (IVF-ET) is considered a method of last resort for treating infertility. Oocytes taken from a woman are fertilized in vitro, and one or more resulting embryos are transferred into the uterus, with the hope that at least one will implant and result in pregnancy. Successful implantation depends on both embryo viability and uterine receptivity. This has led to the development of the EU model for embryo implantation, wherein uterine receptivity is characterized by a latent binary variable U and embryo viability is characterized by a latent binomial variable E representing the number of viable embryos among those selected for transfer. The observed number of implantations is the product of E and U. Zhou and Weinberg (1998) developed a regression formulation of the EU model in which embryo viabilities are independent within patients. We extend their methodology to a Bayesian hierarchical framework that allows for correlation between the embryo viabilities and gives explicit characterization of patient-level heterogeneity. When some subjects have zero implantations, the likelihood for the hierarchical EU model is relatively flat and therefore using prior information for key parametersis needed. This provides a key motivation for adopting a Bayesian approach. The model is used to assess the effect of hydrosalpinx on embryo implantation in a cohort of 288 women undergoing IVF-ET because of tubal disease. Hydrosalpinx is a build-up of fluid in the Fallopian tubes, which sometimes leaks to the uterus and may reduce the likelihood of implantation. The EU model is well suited to this question because hydrosalpinx is thought to affect implantation by reducing uterine receptivity only. Our analysis indicates substantial subject-level heterogeneity with respect to embryo viability, suggesting the utility of a multi-level model.     

鼠衣原体在不同遗传背景小鼠中病变差异性与炎症细胞动态变化

【目的】初步分析鼠衣原体(Chlamydia muridarum,Cm)致不同遗传背景小鼠生殖道病变的原因,探讨炎症细胞动态变化在衣原体感染致不同人群病变差异的可能机制。【方法】用2×105 Inclusion forming units(IFUs)/小鼠的Cm剂量经子宫角(Intrauterine inoculation,iu)途径分别感染DBA/2J鼠和A/J鼠;在感染60 d处死两组小鼠,肉眼观察其输卵管水肿程度,显微镜下观察评估输卵管的扩张程度及炎症反应程度;每组小鼠在感染后3、7、14、21、28、35、42、49、56、60 d分别取阴道分泌物并检测其中衣原体包涵体的数量;在第14天每组各处死5只小鼠,检测上生殖道(输卵管及卵巢)组织匀浆中衣原体包涵体数量及炎症因子水平;同时,在3、28、35 d每组分别处死5只小鼠,显微镜下鉴定病变组织炎症细胞种类及变化。【结果】两组小鼠在感染60 d肉眼观察下的生殖道病变率有明显统计学差异,且两组小鼠病变组织的输卵管扩张程度也具有统计学差异,但炎症反应程度评分无统计学差异;DBA/2J与A/J两组小鼠在阴道分泌物的衣原体包涵体检测及小鼠阳性检出率中并无显著性差异;感染后14 d两组小鼠在上生殖道组织匀浆中的包涵体检出量无统计学差异,但某些炎症因子水平具有统计学差异;感染早期两组小鼠病变组织中嗜中性粒细胞浸润增加,但无明显差异,第28天DBA/2J小鼠病变组织中出现较多嗜酸性粒细胞,并在第35天与A/J小鼠形成统计学差异。【结论】DBA/2J与A/J小鼠在以iu方式感染等量Cm后,引起小鼠的生殖道病变差异可能与嗜酸性粒细胞参与的炎症反应有关。     

IL-6-mediated signaling pathways limit Chlamydia muridarum infection and exacerbate its pathogenicity in the mouse genital tract

Chlamydia muridarum induction of mouse hydrosalpinx, depending on both tubal infection and inflammation, has been used for investigating Chlamydia trachomatis pathogenesis. We now report that IL-6 both inhibits C. muridarum infection and exacerbates pathogenicity in the mouse genital tract. When intravaginally inoculated with a high dose of C. muridarum, IL-6-deficient mice developed more extensive genital tract infection with severe hydrosalpinx, suggesting that IL-6 is required for controlling the high dose infection but not essential for C. muridarum-induced pathology. However, at a low dose, IL-6-deficient mice still developed more extensive infection in the genital tract but no longer with significant pathology, suggesting that IL-6 is required for both controlling the low dose infection and exacerbating the low dose infection-induced pathology. The lack of hydrosalpinx in IL-6-deficient mice correlated with significantly reduced inflammatory infiltration in the oviduct tissue and decreased spleen CD4+ and CD8+ T cells that produce TNFα. Thus, IL-6-dependent pathways are important for both limiting chlamydial colonization in the genital tract mucosal tissues regardless of the infection doses and exacerbating chlamydial pathogenicity in the upper genital tract when IL-6-independent pathogenic mechanisms are not yet activated with a low infection dose.