Sperm miR-34c-5p Transcript Content and Its Association with Sperm Parameters in Unexplained Infertile Men

Dorostghoal, Mehran; Galehdari, Hamid; Hemadi, Masoud; Davoodi, Elahe

doi:10.1007/s43032-021-00733-w

Cited by 4 publications

(5 citation statements)

References 43 publications

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“…In animal models [ 37 ] and in humans [ 38 ] was reported correlation between seminal miR-34c-5p and sperm concentration, total motility, and normal morphology. The expression of miR-34c-5p is significantly lower in spermatozoa of men with several cases of spermatogenic impairment: oligozoospermia, asthenozoospermia, teratozoospermia, oligoasthenoteratozoospermia, idiopathic male infertility and also in seminal plasma of obstructive and nonobstructive azoospermia [ 8 , 39 , 40 , 41 ]. The miR-34c profile is often associated with miR-449b, which belongs to the miR-449a/b/c family.…”

Section: Discussionmentioning

confidence: 99%

“…The miR-34c and miR-449b belong to two different clusters and are transcribed from different loci but have similarities in sequence and therefore share targets and functions. Both are co-expressed in the testis and are downregulated under different conditions of spermatogenic impairment [ 8 ]. Several studies have suggested that alterations in the expression of miR-34c and miR-449b family members negatively affect male reproductive potential because of their involvement in biological processes such as spermatogenesis, fertilization, and embryo development [ 21 , 36 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

“…Although these miRNAs are from different families with different transcriptional loci, they have similar sequences and hence share both targets and functions. Members of both families are co-expressed in the testes and they are both downregulated in various sperm disorders [ 8 ]. Here, miR-449b, which is highly expressed in sperm, improves the first cleavage division, epigenetic reprogramming and apoptotic status of embryos [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Sperm DNA Fragmentation and Sperm-Borne miRNAs: Molecular Biomarkers of Embryo Development?

Conflitti

Cicolani

Buonacquisto

et al. 2023

IJMS

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The evaluation of morpho-functional sperm characteristics alone is not enough to explain infertility or to predict the outcome of Assisted Reproductive Technologies (ART): more sensitive diagnostic tools are needed in clinical practice. The aim of the present study was to analyze Sperm DNA Fragmentation (SDF) and sperm-borne miR-34c-5p and miR-449b-5p levels in men of couples undergoing ART, in order to investigate any correlations with fertilization rate, embryo quality and development. Male partners (n = 106) were recruited. Semen analysis, SDF evaluation and molecular profiling analysis of miR-34c-5p and miR-449b-5p (in 38 subjects) were performed. Sperm DNA Fragmentation evaluation- a positive correlation between SDF post sperm selection and the percentage of low-quality embryos and a negative correlation with viable embryo were found. SDF > 2.9% increased the risk of obtaining a non-viable embryo by almost 4-fold. Sperm miRNAs profile—we found an association with both miRNAs and sperm concentration, while miR-449b-5p is positively associated with SDF. Moreover, the two miRNAs are positively correlated. Higher levels of miR-34c-5p compared to miR-449b-5p increases by 14-fold the probability of obtaining viable embryos. This study shows that SDF, sperm miR-34c-5p, and miR-449b-5p have a promising role as biomarkers of semen quality and ART outcome.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Sperm DNA Fragmentation and Sperm-Borne miRNAs: Molecular Biomarkers of Embryo Development?

Conflitti

Cicolani

Buonacquisto

et al. 2023

IJMS

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show abstract

“…The highest frequencies of methylation were observed in patients with asthenoteratozoospermia (92.9%) and oligoasthenoteratozoospermia (93.8%). Men with low miR-34c-5p expression exhibited low sperm motility and normal sperm morphology ( 34 ).…”

Section: Mirnas and Abnormal Sperm Qualitymentioning

confidence: 99%

MicroRNAs in spermatogenesis dysfunction and male infertility: clinical phenotypes, mechanisms and potential diagnostic biomarkers

Shi,

Yu,

Guo

et al. 2024

Front. Endocrinol.

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Infertility affects approximately 10–15% of couples worldwide who are attempting to conceive, with male infertility accounting for 50% of infertility cases. Male infertility is related to various factors such as hormone imbalance, urogenital diseases, environmental factors, and genetic factors. Owing to its relationship with genetic factors, male infertility cannot be diagnosed through routine examination in most cases, and is clinically called ‘idiopathic male infertility.’ Recent studies have provided evidence that microRNAs (miRNAs) are expressed in a cell-or stage-specific manner during spermatogenesis. This review focuses on the role of miRNAs in male infertility and spermatogenesis. Data were collected from published studies that investigated the effects of miRNAs on spermatogenesis, sperm quality and quantity, fertilization, embryo development, and assisted reproductive technology (ART) outcomes. Based on the findings of these studies, we summarize the targets of miRNAs and the resulting functional effects that occur due to changes in miRNA expression at various stages of spermatogenesis, including undifferentiated and differentiating spermatogonia, spermatocytes, spermatids, and Sertoli cells (SCs). In addition, we discuss potential markers for diagnosing male infertility and predicting the varicocele grade, surgical outcomes, ART outcomes, and sperm retrieval rates in patients with non-obstructive azoospermia (NOA).

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“…Liu et al, (2012) showed that higher levels of miR-34c were associated with higher fertility in mouse, while Fagerlind et al, (2015) reported that lower levels were associated with high fertility in bovine [60,74]. In humans, miR-34c is significantly lower in sperm from men diagnosed with different forms of spermatogenic abnormalities, including oligozoospermia, asthenozoospermia, teratozoospermia, oligoasthenoteratozoospermia, idiopathic male infertility, and in the seminal plasma of obstructive and nonobstructive azoospermia [73,[166][167][168][169]. Levels of miR-34c in sperm have also been correlated with ART outcomes.…”

Section: Plos Onementioning

confidence: 99%

THC and sperm: Impact on fertilization capability, pre-implantation in vitro development and epigenetic modifications

Kuzma-Hunt,

Sabry,

Davis

et al. 2024

PLoS ONE

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Global cannabis use has risen 23% since 2010, with 209 million reported users, most of whom are males of reproductive age. Delta-9-tetrahydrocannabinol (THC), the main psychoactive phytocannabinoid in cannabis, disrupts pro-homeostatic functions of the endocannabinoid system (ECS) within the male reproductive system. The ECS is highly involved in regulating morpho-functional and intrinsic sperm features that are required for fertilization and pre-implantation embryo development. Previous work by our group demonstrated that THC altered sperm capacitation and the transcriptome, including several fertility-associated microRNAs (miRs). Despite the prevalent use of cannabis among males of reproductive age, clinical and pre-clinical research investigating the impact of paternal cannabis on sperm function and the outcomes of artificial reproductive technologies (ARTs) remains inconclusive. Therefore, the present study investigates the impact of in vitro THC exposure on morpho-functional and intrinsic sperm functions, including contributions to embryo development following IVF. Bovine sperm were used as a translational model for human and treated with concentrations of THC that reflect plasma levels after therapeutic (0.032μM), and low (0.32μM)-high (4.8μM) recreational cannabis use. After 6-hours of treatment, THC did not alter the acrosomal reaction, but 4.8μM significantly reduced mitochondrial membrane potential (MMP) (p<0.05), primarily through agonistic interactions with CB-receptors. Fertilization of bovine oocytes with THC-treated sperm did not alter developmental rates, but blastocysts generated from sperm treated with 0.32–4.8μM THC had fewer trophoblasts (p<0.05), while blastocysts generated from sperm exposed to any concentration of THC had fewer cells in the inner cell mass (ICM), particularly within the 0.032μM group (p<0.001). Fertility associated miRs, including miR-346, miR-324, miR-33b, and miR-34c were analyzed in THC-exposed sperm and associated blastocysts generated by IVF, with lower levels of miRs-346, -324, and -33b found in sperm treated with 0.32μM THC, while miR-34c levels were higher in sperm treated with 0.032μM THC (p<0.05). Levels of miR-346 were also lower in sperm treated with 0.032μM THC, but higher in blastocysts generated from sperm exposed to 0.32μM THC (p<0.05). Our findings suggest that THC may alter key morpho-functional and epigenetic sperm factors involved in fertilization and embryo development. This is the first study to demonstrate that sperm exposed to THC in vitro negatively affects embryo quality following IVF.

show abstract

Sperm miR-34c-5p Transcript Content and Its Association with Sperm Parameters in Unexplained Infertile Men

Cited by 4 publications

References 43 publications

Sperm DNA Fragmentation and Sperm-Borne miRNAs: Molecular Biomarkers of Embryo Development?

Sperm DNA Fragmentation and Sperm-Borne miRNAs: Molecular Biomarkers of Embryo Development?

MicroRNAs in spermatogenesis dysfunction and male infertility: clinical phenotypes, mechanisms and potential diagnostic biomarkers

THC and sperm: Impact on fertilization capability, pre-implantation in vitro development and epigenetic modifications

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