The non-coding genome has been extensively studied for its role in human development and diseases. MicroRNAs (miRNAs) are small non-coding RNAs, which can regulate the expression of hundreds of genes at the post-transcriptional level. Therefore, any defects in miRNA biogenesis or processing can affect the genes and have been linked to several diseases. Male infertility is a clinical disorder with a significant number of cases being idiopathic. Problems in spermatogenesis and epididymal maturation, testicular development, sperm maturation or migration contribute to male infertility, and many of these idiopathic cases are related to issues with the miRNAs which tightly regulate these processes. This review summarizes the recent research on various such miRNAs and puts together the candidate miRNAs that may be used as biomarkers for diagnosis. The development of strategies for male infertility treatment using anti-miRs or miRNA mimics is also discussed. Although promising, the development of miRNA diagnostics and therapeutics is challenging, and ways to overcome some of these challenges are also reviewed.

Structural heterogeneity in the native‐state ensemble of dSmt3, the only small ubiquitin‐like modifier (SUMO) in Drosophila melanogaster, was investigated and compared with its human homologue SUMO1. Temperature dependence of amide proton's chemical shift was studied to identify amino acids possessing alternative structural conformations in the native state. Effect of small concentration of denaturant (1M urea) on this population was also monitored to assess the ruggedness of near‐native energy landscape. Owing to presence of many such amino acids, especially in the β2‐loop‐α region, the native state of dSmt3 seems more flexible in comparison to SUMO1. Information about backbone dynamics in ns‐ps timescale was quantified from the measurement of 15N‐relaxation experiments. Furthermore, the noncovalent interaction of dSmt3 and SUMO1 with Daxx12 (Daxx729DPEEIIVLSDSD740), a [V/I]‐X‐[V/I]‐[V/I]‐based SUMO interaction motif, was characterized using Bio‐layer Interferometery and NMR spectroscopy. Daxx12 fits itself in the groove formed by β2‐loop‐α structural region in both dSmt3 and SUMO1, but the binding is stronger with the former. Flexibility of β2‐loop‐α region in dSmt3 is suspected to assist its interaction with Daxx12. Our results highlight the role of native‐state flexibility in assisting noncovalent interactions of SUMO proteins especially in organisms where a single SUMO isoform has to tackle multiple substrates single handedly.

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(1) Background: The relationships between the biochemical and immunological components in seminal plasma and their physiological effects on male reproductive system have been underreported. In this study, we evaluated the potential of several seminal plasma biochemical and immunological markers in the pathophysiological developments of the infertile male patients. The study was designed to identify and assess different markers that may be associated with semen functions in different types of male infertility. (2) Methods: A total of 50 infertile male patients who underwent checkup for fertility assessment and 50 fertile controls were included in this study. The complete medical history of each recruited participant was reviewed. The infertile sub-groups (non-obstructive azoospermia (NOA), asthenozoospermia (AS), normozoospermic infertile (NI), and oligozoospermia (OZ)) were characterized based on sperm motility and concentration, while NI patients were included after a thorough check up of their female partners as well. We investigated each sample for 21 different analytes, enzymes, trace elements, and immunological markers to find crucial markers posing as contributing factors to a specific type of male infertility. (3) Results: The levels of 15 out of 21 markers, assayed from the seminal plasma of infertile males, were significantly altered in comparison to fertile controls (p < 0.05). For the first time, microprotein levels were also analyzed. The presence of monocytes, lymphocytes, and granulocytes was limited to semen from NOA patients, while a significant increase in the level of platelets was observed in AS. Hierarchical clustering and ROC-AUC analysis identified the three most significant markers (zinc, LDH, and TG) for the healthy control group and asthenozoospermic group (AUC, of 0.92 and 0.81, respectively). (4) Conclusions: The altered levels of biochemical and immunological markers in seminal plasma might be associated with the different male infertility profiles and could be required for the sperm metabolism and maintenance. However, a larger sample size and follow up analysis is required for establishing the hypothesized panel of markers as biomarkers at clinical stage.

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