Urinary estrogen metabolites and self-reported infertility in women infected with Schistosoma haematobium.
BACKGROUND
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.


RESULTS
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
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.
Clínica da Sagrada Esperança, Luanda, Angola.
Júlio
J
Santos
CIQUP, Chemistry and Biochemistry Department, Faculty of Sciences, University of Porto, Porto, Portugal.
Maria João
MJ
Gouveia
CIQUP, Chemistry and Biochemistry Department, Faculty of Sciences, University of Porto, Porto, Portugal.
Nuno
N
Vale
INSA, National Institute of Health, Porto, Portugal.
Maria de Lurdes
Mde L
Delgado
Centre for Reproductive Genetics Prof. Alberto Barros, Porto, Portugal.
Ana
A
Gonçalves
Centre for Reproductive Genetics Prof. Alberto Barros, Porto, Portugal.
José M Teixeira
JM
da Silva
Centre for Reproductive Genetics Prof. Alberto Barros, Porto, Portugal.
Cristiano
C
Oliveira
Centre for Reproductive Genetics Prof. Alberto Barros, Porto, Portugal.
Pedro
P
Xavier
CIQUP, Chemistry and Biochemistry Department, Faculty of Sciences, University of Porto, Porto, Portugal.
Paula
P
Gomes
Clínica da Sagrada Esperança, Luanda, Angola; Experimental Therapeutics and Pathology Research Group, Portuguese Institute of Oncology, Porto, Portugal.
Lúcio L
LL
Santos
Clínica da Sagrada Esperança, Luanda, Angola; Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
Carlos
C
Lopes
Centre for Reproductive Genetics Prof. Alberto Barros, Porto, Portugal; Department of Genetics, Faculty of Medicine, University of Porto, Porto, Portugal.
Alberto
A
Barros
Department of Microbiology, Immunology and Tropical Medicine, and Research Center for Neglected Diseases of Poverty, School of Medicine & Health Sciences, George Washington University, Washington, D.C., United States of America; Departamento de Genética, Facultad de Medicina, Universidad de la República, (UDELAR), Montevideo, Uruguay.
Gabriel
G
Rinaldi
Department of Microbiology, Immunology and Tropical Medicine, and Research Center for Neglected Diseases of Poverty, School of Medicine & Health Sciences, George Washington University, Washington, D.C., United States of America.
Paul J
PJ
Brindley
INSA, National Institute of Health, Porto, Portugal; Center for the Study of Animal Science, CECA/ICETA, University of Porto, Porto, Portugal.
José M Correia
JM
da Costa
Department of Microscopy, Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar (ICBAS), Multidisciplinary Unit for Biomedical Research-UMIB, University of Porto, Porto, Portugal.
Mário
M
Sousa
INSA, National Institute of Health, Porto, Portugal; Center for the Study of Animal Science, CECA/ICETA, University of Porto, Porto, Portugal.
Mónica C
MC
Botelho
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000810:Angola / Q000453:epidemiology; D000818:Animals; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D018736:DNA Adducts / Q000652:urine; D004967:Estrogens / Q000652:urine*; D005260:Female; D006801:Humans; D007247:Infertility, Female / Q000150:complications / Q000453:epidemiology / Q000469:parasitology / Q000652:urine*; D008875:Middle Aged; D010270:Parasite Egg Count; D012548:Schistosoma haematobium / Q000302:isolation & purification* / Q000378:metabolism / Q000472:pathogenicity; D012553:Schistosomiasis haematobia / Q000150:complications / Q000453:epidemiology / Q000469:parasitology / Q000652:urine*; D057566:Self Report; D014551:Urinary Tract / Q000469:parasitology
D018736:DNA Adducts; D004967:Estrogens