Omics and Male Infertility: Highlighting the Application of Transcriptomic Data

Abstract

Male infertility is a multifaceted disorder affecting approximately 50% of male partners in infertile couples. Over the years, male infertility has been diagnosed mainly through semen analysis, hormone evaluations, medical records and physical examinations, which of course are fundamental, but yet inefficient, because 30% of male infertility cases remain idiopathic. This dilemmatic status of the unknown needs to be addressed with more sophisticated and result-driven technologies and/or techniques. Genetic alterations have been linked with male infertility, thereby unveiling the practicality of investigating this disorder from the “omics” perspective. Omics aims at analyzing the structure and functions of a whole constituent of a given biological function at different levels, including the molecular gene level (genomics), transcript level (transcriptomics), protein level (proteomics) and metabolites level (metabolomics). In the current study, an overview of the four branches of omics and their roles in male infertility are briefly discussed; the potential usefulness of assessing transcriptomic data to understand this pathology is also elucidated. After assessing the publicly obtainable transcriptomic data for datasets on male infertility, a total of 1385 datasets were retrieved, of which 10 datasets met the inclusion criteria and were used for further analysis. These datasets were classified into groups according to the disease or cause of male infertility. The groups include non-obstructive azoospermia (NOA), obstructive azoospermia (OA), non-obstructive and obstructive azoospermia (NOA and OA), spermatogenic dysfunction, sperm dysfunction, and Y chromosome microdeletion. Findings revealed that 8 genes (LDHC, PDHA2, TNP1, TNP2, ODF1, ODF2, SPINK2, PCDHB3) were commonly differentially expressed between all disease groups. Likewise, 56 genes were common between NOA versus NOA and OA (ADAD1, BANF2, BCL2L14, C12orf50, C20orf173, C22orf23, C6orf99, C9orf131, C9orf24, CABS1, CAPZA3, CCDC187, CCDC54, CDKN3, CEP170, CFAP206, CRISP2, CT83, CXorf65, FAM209A, FAM71F1, FAM81B, GALNTL5, GTSF1, H1FNT, HEMGN, HMGB4, KIF2B, LDHC, LOC441601, LYZL2, ODF1, ODF2, PCDHB3, PDHA2, PGK2, PIH1D2, PLCZ1, PROCA1, RIMBP3, ROPN1L, SHCBP1L, SMCP, SPATA16, SPATA19, SPINK2, TEX33, TKTL2, TMCO2, TMCO5A, TNP1, TNP2, TSPAN16, TSSK1B, TTLL2, UBQLN3). These genes, particularly the above-mentioned 8 genes, are involved in diverse biological processes such as germ cell development, spermatid development, spermatid differentiation, regulation of proteolysis, spermatogenesis and metabolic processes. Owing to the stage-specific expression of these genes, any mal-expression can ultimately lead to male infertility. Therefore, currently available data on all branches of omics relating to male fertility can be used to identify biomarkers for diagnosing male infertility, which can potentially help in unravelling some idiopathic cases.

Whole-Genome Profile of Greek Patients with Teratozοοspermia: Identification of Candidate Variants and Genes

“…For many of the highlighted genes with prioritized variants, there are indications of their involvement in male infertility, but further research is needed to investigate their exact role. Some of them are centrosomal protein 170 ( CEP170 ) [ 50 ], gametogenetin ( GGN ) that is a testis-enriched gene [ 51 ], ghrelin, and obestatin, identified in human semen and the male reproductive system in general [ 52 , 53 ], Janus Kinase 1 ( JAK1 ), found in the midpiece of spermatozoa and activated during capacitation [ 54 , 55 ], the lipopolysaccharide-binding protein that it is found in sperm and tail of spermatozoa [ 56 ] and tyrosine-kinase 2 ( TYK2 ) that is active in human sperm [ 57 ] and plays a role in crucial signaling pathways. TET2 is also expressed in the cytoplasm of late pachytene spermatocytes of Stage V and there are indications that its expression levels are associated with fertility status and sperm parameters [ 58 ].…”

Multi-omics analysis reveals prognostic and therapeutic value of cuproptosis-related lncRNAs in oral squamous cell carcinoma

“…Accurately predicting HNSCC outcomes and developing new therapeutic targets can be achieved with AC090587.2 and AL513190.1 ( Zhou et al, 2022 ). There is evidence that C6orf99 is involved in diverse biological processes including spermatogenesis and development of spermatogonia that plays a key role in male infertility ( Omolaoye et al, 2022 ). Moreover, the prognostic prediction of patients with HNSCC may also be affected by AC010894.2, which may serve as a potential therapeutic target ( Lu et al, 2022 ).…”

The role of sperm mitochondria in the occurrence and development of male infertility

“…В серии «омиксных» исследований, выполненных в последнее время, получены доказательства ведущей роли в развитии тяжелых форм мужского бесплодия абер-рантной экспрессии белков митохондрий, причастных, прежде всего, к энергопродукции, регуляции апоптоза и митофагии [22][23][24][25][26][27]. Так, у пациентов с повторными неудачными исходами оплодотворения после ИКСИ выявлены множественные дефекты митохондриальных белков: ферментов пируватдегидрогеназного комплекса (дигидролипоилтрансацетилазы -DLAT, пируватдегидрогеназы -PDHA) и цикла трикарбоновых кислот (фумаратгидратазы -FH); АТФ-синтазы (дельта-субъединицы F 1 -компонента -ATP5F1D и D-субъединицы F o -компонента -ATP5H); переносчика фосфат-ионов (SLC25A3); транслоказы адениловых нуклеотидов (ANT4); прохибитина 2-го типа (PHB2) и др.…”

“…Оценка доступных в открытых источниках транскриптомных данных по всему спектру нарушений мужской репродуктивной функции, включая необструктивную и обструктивную азооспермию, их комбинацию, а также микроделецию Y-хромосомы, для идентификации дифференциально экспрессированных генов и их продуктов, дала возможность верифицировать потенциальные маркерные белки идиопатического бесплодия [27]. Авторами подтверждена патогенетическая значимость пируватдегидрогеназного комплекса и ансамбля ассоциированных с ним белков, 13 из которых вовлечены в энергетический метаболизм (спермспецифическая лактатдегидрогеназа С, аденилаттранслоказа ANT4, F o -компонент и альфа-субъединица F 1 -компонента АТФ-синтазы, транслоказа внутренней мембраны митохондрий -TIM4 и др.…”