@article{3029798,
    title = "Investigating the Role of the microRNA-34/449 Family in Male
Infertility: A Critical Analysis and Review of the Literature",
    author = "Pantos, Konstantinos and Grigoriadis, Sokratis and Tomara, Penelope and and Louka, Ioanna and Maziotis, Evangelos and Pantou, Agni and Nitsos, and Nikolaos and Vaxevanoglou, Terpsithea and Kokkali, Georgia and Agarwal, and Ashok and Sfakianoudis, Konstantinos and Simopoulou, Mara",
    journal = "FRONTIERS IN ENDOCRINOLOGY",
    year = "2021",
    volume = "12",
    publisher = "Frontiers Media SA",
    doi = "10.3389/fendo.2021.709943",
    keywords = "male infertility; idiopathic male infertility; micro-ribonucleic acids
(microRNAs); miR-34/449; spermatogenesis; ciliogenesis; biomarkers;
personalized medicine",
    abstract = "There is a great body of evidence suggesting that in both humans and
animal models the microRNA-34/449 (miR-34/449) family plays a crucial
role for normal testicular functionality as well as for successful
spermatogenesis, regulating spermatozoa maturation and functionality.
This review and critical analysis aims to summarize the potential
mechanisms via which miR-34/449 dysregulation could lead to male
infertility. Existing data indicate that miR-34/449 family members
regulate ciliogenesis in the efferent ductules epithelium. Upon
miR-34/449 dysregulation, ciliogenesis in the efferent ductules is
significantly impaired, leading to sperm aggregation and agglutination
as well as to defective reabsorption of the seminiferous tubular fluids.
These events in turn cause obstruction of the efferent ductules and thus
accumulation of the tubular fluids resulting to high hydrostatic
pressure into the testis. High hydrostatic pressure progressively leads
to testicular dysfunction as well as to spermatogenic failure and
finally to male infertility, which could range from severe
oligoasthenozoospermia to azoospermia. In addition, miR-34/449 family
members act as significant regulators of spermatogenesis with an
essential role in controlling expression patterns of several
spermatogenesis-related proteins. It is demonstrated that these
microRNAs are meiotic specific microRNAs as their expression is
relatively higher at the initiation of meiotic divisions during
spermatogenesis. Moreover, data indicate that these molecules are
essential for proper formation as well as for proper function of
spermatozoa per se. MicroRNA-34/449 family seems to exert significant
anti-oxidant and anti-apoptotic properties and thus contribute to
testicular homeostatic regulation. Considering the clinical significance
of these microRNAs, data indicate that the altered expression of the
miR-34/449 family members is strongly associated with several aspects of
male infertility. Most importantly, miR-34/449 levels in spermatozoa, in
testicular tissues as well as in seminal plasma seem to be directly
associated with severity of male infertility, indicating that these
microRNAs could serve as potential sensitive biomarkers for an accurate
individualized differential diagnosis, as well as for the assessment of
the severity of male factor infertility. In conclusion, dysregulation of
miR-34/449 family detrimentally affects male reproductive potential,
impairing both testicular functionality as well as spermatogenesis.
Future studies are needed to verify these conclusions."
}