Epigenetics of Male Fertility: Effects on Assisted Reproductive Techniques

Giacone, Filippo; Cannarella, Rossella; Mongioì, Laura M.; Alamo, Angela; Condorelli, Rosita A.; Calogero, Aldo E.; Vignera, Sandro La

doi:10.5534/wjmh.180071

Cited by 48 publications

(63 citation statements)

References 76 publications

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“…This hypothesis is supported by the expression of IGF2 mRNA into human spermatozoa [24], and the homonym protein plays a role in prenatal fetal development. As a growth factor, IGF2 may play a role in the cellular mitosis of the embryo [25]. Furthermore, since the expression of IGF2 depends on the promotor methylation rate, which the embryo receives from the spermatozoon, it may be speculated that sperm-expressed IGF2 plays a role in embryo growth at the very early stage of embryo formation before EGA.…”

Section: Discussionmentioning

confidence: 99%

“…However, the evidence has shown that parental imprinted regions escape from demethylation, although the reason for this is not fully understood [23]. Some researchers hypothesized that paternally-expressed imprinted genes (e.g., IGF2, a sperm-carried transcript [24]) may be of particular importance in preimplantation embryo development [25]. Accordingly, the involvement of imprinted genes in embryo and placenta development and growth is well acknowledged in mice.…”

Section: Physiology Of Fertilization and Embryo Developmentmentioning

confidence: 99%

“…The sperm genome is highly packaged by protamines, which replace histones during spermatogenesis. This process, which is typical of spermatozoa, is called protamination and ensures significant DNA compaction, resulting in protection from external insults and gene silencing [25]. Abnormal sperm protamination represents one of the mechanisms by which sperm DNA integrity can be affected, with consequent defective development of the embryo.…”

Section: Sperm Genomementioning

confidence: 99%

“…Spermatozoa carry thousands of different RNAs-such as messenger RNA (mRNA), micro-RNA (miRNA), interference RNA (iRNA), antisense RNA and long non-coding RNA-and more than 4000 different mRNAs [25]. Human sperm transcription of the paternally-derived imprinted gene IGF2 has been demonstrated [24].…”

Section: Sperm Transcriptomementioning

confidence: 99%

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Molecular Biology of Spermatogenesis: Novel Targets of Apparently Idiopathic Male Infertility

Cannarella

Condorelli

Mongioì

et al. 2020

IJMS

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Male infertility affects half of infertile couples and, currently, a relevant percentage of cases of male infertility is considered as idiopathic. Although the male contribution to human fertilization has traditionally been restricted to sperm DNA, current evidence suggest that a relevant number of sperm transcripts and proteins are involved in acrosome reactions, sperm-oocyte fusion and, once released into the oocyte, embryo growth and development. The aim of this review is to provide updated and comprehensive insight into the molecular biology of spermatogenesis, including evidence on spermatogenetic failure and underlining the role of the sperm-carried molecular factors involved in oocyte fertilization and embryo growth. This represents the first step in the identification of new possible diagnostic and, possibly, therapeutic markers in the field of apparently idiopathic male infertility.

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Section: Discussionmentioning

confidence: 99%

Section: Physiology Of Fertilization and Embryo Developmentmentioning

confidence: 99%

Section: Sperm Genomementioning

confidence: 99%

Section: Sperm Transcriptomementioning

confidence: 99%

See 2 more Smart Citations

Molecular Biology of Spermatogenesis: Novel Targets of Apparently Idiopathic Male Infertility

Cannarella

Condorelli

Mongioì

et al. 2020

IJMS

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“…Thousands of different RNAs (including coding and non-coding RNAs) have been detected in human spermatozoa [3]. As indicators of sperm transcriptional activity [4,5], RNAs in these cells likely derive from unmethylated or hypomethylated genes, which the transcriptional apparatus can access [1]. Several genes have been found to be differentially methylated in infertile patients compared to controls, and the most investigated pair of differentially methylated genes is H19/IGF2 [2].…”

Section: Introductionmentioning

confidence: 99%

IGF2 and IGF1R mRNAs Are Detectable in Human Spermatozoa

Cannarella

Condorelli

Vignera

et al. 2020

World J Mens Health

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Purpose: Oligozoospermia is highly prevalent worldwide. Studies have reported a lower methylation rate in the H19 differentially methylated region at the sperm level in oligozoospermic patients than in controls. IGF2/H19 are the best-known pair of imprinted genes. However, no studies have yet evaluated whether they are transcribed in human sperm. To assess whether IGF2 and IGF1R mRNAs are present in human sperm and if their levels are correlated with sperm concentration and total sperm count. Materials and Methods: Sperm samples (n=22) underwent reverse-transcription quantitative polymerase chain reaction using specific primers to detect IGF2 and IGF1R mRNA levels. They were then correlated with patients' conventional sperm parameters using the Spearman (τ) and Kendall (ρ) rank correlation coefficients. Results: Statistically significant positive correlations were found between IGF2 mRNA levels and sperm concentration (τ= 0.403, p<0.01; ρ=0.587, p<0.005) and total sperm count (τ=0.347, p<0.024; ρ=0.509, p<0.015). IGF1R mRNA levels were positively correlated with sperm concentration (τ=0.595, p<0.001; ρ=0.774, p<0.001) and total sperm count (τ=0.547, p< 0.001; ρ=0.701, p<0.001). Apart from IGF1R mRNA and sperm morphology (τ=0.325, p<0.05; ρ=0.461, p<0.05), no additional correlations were found between the levels of these transcripts and other conventional sperm parameters. Conclusions: IGF2 and IGF1R mRNAs were found to be present in human spermatozoa and their transcription levels were positively correlated with sperm concentration and total sperm count. Spermatozoa are the only source of IGF2 mRNA since IGF2 is a paternally-inherited gene. Further studies are needed to evaluate its role in human fertilization.

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Sperm chromatin condensation and single‐ and double‐stranded DNA damage as important parameters to define male factor related recurrent miscarriage

Ribas-Maynou

Abad

Garcia-Segura

et al. 2020

Molecular Reproduction Devel

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The aim of the present work is to characterize the relationship between sperm protamine deficiency and single-and double-stranded DNA damage and to assess the diagnostic potential of chromomycin A3 (CMA3). For that purpose, semen samples from 90 human males with different clinical features were included (fertile donors, patients with recurrent pregnancy loss [RPL], and infertile patients). DNA condensation was analyzed by CMA3 and different types of DNA fragmentation were analyzed through the comet assay. A positive correlation between DNA condensation and single-stranded DNA fragmentation was found (Rs = .456; p = .05). CMA3 presented differences between fertile donors and all other groups (p < .001). Interestingly, patients with RPL, who were able to achieve a pregnancy, and infertile patients showed similar values of CMA3 (p > .05). Receiver operating characteristic curves and the profiles obtained by the combination of Comet assays and CMA3 indicate that the CMA3 test may be an interesting approach to distinguish those subjects with higher pregnancy loss risk from fertile donors (CMA3 area under the curve 0.928, with a confidence interval of 0.849-1.000). The present work shows that DNA condensation is related to oxidative damage, which affects mainly protamine-rich regions. The profiles observed in different clinical groups showed that CMA3 might be useful for the diagnosis of RPL risk when combined with Comet assays.

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Epigenetics of Male Fertility: Effects on Assisted Reproductive Techniques

Cited by 48 publications

References 76 publications

Molecular Biology of Spermatogenesis: Novel Targets of Apparently Idiopathic Male Infertility

Molecular Biology of Spermatogenesis: Novel Targets of Apparently Idiopathic Male Infertility

IGF2 and IGF1R mRNAs Are Detectable in Human Spermatozoa

Sperm chromatin condensation and single‐ and double‐stranded DNA damage as important parameters to define male factor related recurrent miscarriage

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