p.p1 to east-west countries [Fig. 1A]. Between

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INTRODUCTIONDuring
the second half of the twentieth century, the incidence of testicular cancer (TC) has
increased significantly and unevenly in industrialized countries. This cancer has become the
first young man’s cancer in many countries of northern Europe and there is a gradual
increasing incidence of testicular cancer from north-south gradient to east-west countries
Fig. 1A. Between 1960s and 2010, the Total Fertility Rate (TFR) per woman in Japan has
fallen below 2.1. In USA and Europe, TFR was above 3.5 and 2.5 but nowadays it has
dropped to replacement level and below the normal level respectively. It has been
hypothesized that this decreased female fecundity is linked to global decreased male fertility
and a syndromic concept of Testis Dysgenesis Fig. 1B(Skakkebaek et al., 2016). Among the
different types of testis cancer, seminoma which develops from germ cells is the most
frequent one. Sperms are gametes resulting from a long maturation process called
spermatogenesis which comprises meiosis events and DNA modifications as well as shaping.
Spermatogenesis is initiated in seminiferous tubule since the puberty time. Originating cells
are spermatogonia which migrated from the allantoid region to the undifferentiated gonads
during the 7th week of pregnancy.
The last step of spermatogenesis, spermiogenesis is the process of transforming spermatids
into spermatozoa by a series of events: 1) a general shaping by loss of cytoplasm and
development of a functional axonema, 2) an increasing degree of DNA packaging
accompanied with the following events: histones are replaced by transition proteins and
finally by protamines (PRM1 and PRM2), thereby allowing a 10-fold compaction of male
DNA in toroidal nucleoprotamine structures. This replacement of proteins defends the
paternal genome from physico-chemical damages. Moreover, protamines themselves are
involved in epigenetic process (Brunner et al., 2014). Classically, sperm was seen as a
transcriptionally inactive vehicle that only serves to deliver its DNA to the egg. In the late
1980s, despite the apparent transcriptionally inert state of the mature spermatozoa, the
presence of RNA was first described in a plant spermatozoid nucleus (Rejon et al., 1988) and
then in rat and human sperm nuclei (Pessot et al., 1989). Mammalian sperm harbours
diversity of RNA which includes mRNA, miRNA, antisense RNA, piRNA etc. In addition a
recent analysis of a complex sperm RNA surprisingly explains that sperm tsRNAs (tRNA
derived small RNAs specifically 5´tRNA halves) can induce non-mendelian transgenerational
inheritance in mammals

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