1H NMR-based metabonomics for infertility diagnosis in men with varicocele
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REPRODUCTIVE PHYSIOLOGY AND DISEASE
1H NMR-based metabonomics for infertility diagnosis in men with varicocele Filipe Tenorio Lira Neto 1,2 & Ronmilson Alves Marques 3 & Alexandre de Freitas Cavalcanti Filho 2 & Leslie Clifford Noronha Araujo 4 & Salvador Vilar Correia Lima 5 & Licarion Pinto 6 & Ricardo Oliveira Silva 6 Received: 15 October 2019 / Accepted: 16 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose “Omics” techniques have been used to understand and to identify biomarkers of male infertility. We report on the first metabonomics models created to diagnose varicocele and infertility among men with varicocele. Methods We recruited 35 infertile men with varicocele (VI group), 21 fertile men with varicocele (VF group) and 24 fertile men without varicocele (C group). All men underwent standard semen analysis, scrotal duplex ultrasonography, and sexual hormone level measurement. Hydrogen-1 nuclear magnetic resonance (1H NMR) spectra of seminal plasma were used to create metabonomics models to discriminate between men with and without varicocele, and between fertile and infertile men with varicocele. Results Using the statistical formalisms partial least square discriminants analysis and genetic algorithm–based linear discriminant analysis (GA-LDA), we created two models that discriminated the three groups from each other with accuracy of 92.17%. We also created metabonomics models using orthogonal partial least square discriminants analysis and GA-LDA that discriminated VF group from VI group, with an accuracy of 94.64% and 100% respectively. We identified 19 metabolites that were important in group segregation: caprate, 2-hydroxy-3-methylvalerate, leucine, valine, 3-hydroxybutyrate, lactate, alanine, 4aminobutyrate, isoleucine, citrate, methanol, glucose, glycosides, glycerol-3-phosphocoline, n-acetyltyrosine, glutamine, tyrosine, arginine, and uridine. Conclusions 1HNMR-based metabonomics of seminal plasma can be used to create metabonomics models to discriminate between men with varicocele from those without varicocele, and between fertile men with varicocele from those infertile with varicocele. Furthermore, the most important metabolites for group segregation are involved in the oxidative stress caused by varicocele. Keywords Metabolome . Metabolomics . Fertility . Semen . NMR spectroscopy
* Filipe Tenorio Lira Neto [email protected]
1
Department of Surgery, Universidade Federal de Pernambuco, Rua Guilherme Salazar, n 150, apt 601E, Recife, PE ZIP 52061-275, Brazil
Ronmilson Alves Marques [email protected]
2
Instituto de Medicina Integral Prof. Fernando Figueira, Rua dos Coelho, 300, Coelhos, Recife, PE ZIP 50070-902, Brazil
Alexandre de Freitas Cavalcanti Filho [email protected]
3
Fundamental Chemistry Department, Universidade Federal de Pernambuco, Av. Jornalista Anibal Fernandes, s/n° Cidade Universitária, Recife, PE ZIP 50740-560, Brazil
4
Faculdade de Medicina de Olinda, Rua Dr. Manoel de Almeida Belo, n 1333, Olinda, PE ZIP 53030-
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