Santos Júlio, Gouveia Maria João, Vale Nuno, Delgado Maria de Lurdes, Gonçalves Ana, da Silva José M Teixeira, Oliveira Cristiano, Xavier Pedro, Gomes Paula, Santos Lúcio L, Lopes Carlos, Barros Alberto, Rinaldi Gabriel, Brindley Paul J, da Costa José M Correia, Sousa Mário, Botelho Mónica C
Clínica da Sagrada Esperança, Luanda, Angola.
CIQUP, Chemistry and Biochemistry Department, Faculty of Sciences, University of Porto, Porto, Portugal.
PLoS One. 2014 May 21;9(5):e96774. doi: 10.1371/journal.pone.0096774. eCollection 2014.
Schistosomiasis is a neglected tropical disease, endemic in 76 countries, that afflicts more than 240 million people. The impact of schistosomiasis on infertility may be underestimated according to recent literature. Extracts of Schistosoma haematobium include estrogen-like metabolites termed catechol-estrogens that down regulate estrogen receptors alpha and beta in estrogen responsive cells. In addition, schistosome derived catechol-estrogens induce genotoxicity that result in estrogen-DNA adducts. These catechol estrogens and the catechol-estrogen-DNA adducts can be isolated from sera of people infected with S. haematobium. The aim of this study was to study infertility in females infected with S. haematobium and its association with the presence of schistosome-derived catechol-estrogens.
METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional study was undertaken of female residents of a region in Bengo province, Angola, endemic for schistosomiasis haematobia. Ninety-three women and girls, aged from two (parents interviewed) to 94 years were interviewed on present and previous urinary, urogenital and gynecological symptoms and complaints. Urine was collected from the participants for egg-based parasitological assessment of schistosome infection, and for liquid chromatography diode array detection electron spray ionization mass spectrometry (LC/UV-DAD/ESI-MSn) to investigate estrogen metabolites in the urine. Novel estrogen-like metabolites, potentially of schistosome origin, were detected in the urine of participants who were positive for eggs of S. haematobium, but not detected in urines negative for S. haematobium eggs. The catechol-estrogens/ DNA adducts were significantly associated with schistosomiasis (OR 3.35; 95% CI 2.32-4.84; P≤0.001). In addition, presence of these metabolites was positively associated with infertility (OR 4.33; 95% CI 1.13-16.70; P≤0.05).
CONCLUSIONS/SIGNIFICANCE: Estrogen metabolites occur widely in diverse metabolic pathways. In view of the statistically significant association between catechol-estrogens/ DNA adducts and self-reported infertility, we propose that an estrogen-DNA adduct mediated pathway in S. haematobium-induced ovarian hormonal deregulation could be involved. In addition, the catechol-estrogens/ DNA adducts described here represent potential biomarkers for schistosomiasis haematobia.
血吸虫病是一种被忽视的热带疾病，在76个国家流行，折磨着超过2.4亿人。根据最近的文献，血吸虫病对不孕症的影响可能被低估了。埃及血吸虫提取物中含有称为儿茶酚雌激素的雌激素样代谢物，可下调雌激素反应细胞中的雌激素受体α和β。此外，血吸虫衍生的儿茶酚雌激素会诱导基因毒性，导致雌激素-DNA加合物的形成。这些儿茶酚雌激素和儿茶酚雌激素-DNA加合物可以从感染埃及血吸虫的人的血清中分离出来。本研究的目的是研究感染埃及血吸虫的女性的不孕症及其与血吸虫衍生的儿茶酚雌激素的存在之间的关联。
方法/主要发现：对安哥拉本戈省一个血吸虫病流行地区的女性居民进行了一项横断面研究。对93名年龄从2岁（采访父母）到94岁的女性和女孩进行了关于当前和以前的泌尿、泌尿生殖和妇科症状及主诉的访谈。收集参与者的尿液，用于基于虫卵的血吸虫感染寄生虫学评估，并用于液相色谱二极管阵列检测电子喷雾电离质谱法（LC/UV-DAD/ESI-MSn），以研究尿液中的雌激素代谢物。在埃及血吸虫虫卵阳性的参与者尿液中检测到了可能源自血吸虫的新型雌激素样代谢物，但在埃及血吸虫虫卵阴性的尿液中未检测到。儿茶酚雌激素/DNA加合物与血吸虫病显著相关（比值比3.35；95%置信区间2.32-4.84；P≤0.001）。此外，这些代谢物的存在与不孕症呈正相关（比值比4.33；95%置信区间1.13-16.70；P≤0.05）。
结论/意义：雌激素代谢物广泛存在于多种代谢途径中。鉴于儿茶酚雌激素/DNA加合物与自我报告的不孕症之间存在统计学上的显著关联，我们提出埃及血吸虫诱导的卵巢激素失调中可能涉及雌激素-DNA加合物介导的途径。此外，本文所述的儿茶酚雌激素/DNA加合物代表了埃及血吸虫病的潜在生物标志物。
