scholarly journals All you need to know about sperm RNAs

Author(s):  
Joana Santiago ◽  
Joana V Silva ◽  
John Howl ◽  
Manuel A S Santos ◽  
Margarida Fardilha

Abstract BACKGROUND Spermatogenesis generates a small and highly specialised type of cell that is apparently incapable of transcription and translation. For many years, this dogma was supported by the assumption that (i) the compact sperm nucleus, resulting from the substitution of histones by protamine during spermatogenesis, renders the genome inaccessible to the transcriptional machinery; and (ii) the loss of most organelles, including endoplasmic reticulum and ribosomes, limits or prevents translational activity. Despite these observations, several types of coding and non-coding RNAs have been identified in human sperm. Their functional roles, particularly during fertilisation and embryonic development, are only now becoming apparent. OBJECTIVE AND RATIONALE This review aimed to summarise current knowledge of the origin, types and functional roles of sperm RNAs, and to evaluate the clinical benefits of employing these transcripts as biomarkers of male fertility and reproductive outcomes. The possible contribution of sperm RNAs to intergenerational or transgenerational phenotypic inheritance is also addressed. SEARCH METHODS A comprehensive literature search on PubMed was conducted using the search terms ‘sperm’ AND ‘RNA’. Searches focussed upon articles written in English and published prior to August 2020. OUTCOMES The development of more sensitive and accurate RNA technologies, including RNA sequencing, has enabled the identification and characterisation of numerous transcripts in human sperm. Though a majority of these RNAs likely arise during spermatogenesis, other data support an epididymal origin of RNA transmitted to maturing sperm by extracellular vesicles. A minority may also be synthesised by de novo transcription in mature sperm, since a small portion of the sperm genome remains packed by histones. This complex RNA population has important roles in paternal chromatin packaging, sperm maturation and capacitation, fertilisation, early embryogenesis and developmental maintenance. In recent years, additional lines of evidence from animal models support a role for sperm RNAs in intergenerational or transgenerational inheritance, modulating both the genotype and phenotype of progeny. Importantly, several reports indicate that the sperm RNA content of fertile and infertile men differs considerably and is strongly modulated by the environment, lifestyle and pathological states. WIDER IMPLICATIONS Transcriptional profiling has considerable potential for the discovery of fertility biomarkers. Understanding the role of sperm transcripts and comparing the sperm RNA fingerprint of fertile and infertile men could help to elucidate the regulatory pathways contributing to male factor infertility. Such data might also provide a molecular explanation for several causes of idiopathic male fertility. Ultimately, transcriptional profiling may be employed to optimise ART procedures and overcome some of the underlying causes of male infertility, ensuring the birth of healthy children.

Author(s):  
Caili Li ◽  
Meizhen Wang ◽  
Xiaoxiao Qiu ◽  
Hong Zhou ◽  
Shanfa Lu

Background: Noncoding RNAs (ncRNAs), such as microRNAs (miRNAs), small interfering RNAs (siRNAs) and long noncoding RNAs (lncRNAs), play significant regulatory roles in plant development and secondary metabolism and are involved in plant response to biotic and abiotic stresses. They have been intensively studied in model systems and crops for approximately two decades and massive amount of information have been obtained. However, for medicinal plants, ncRNAs, particularly their regulatory roles in bioactive compound biosynthesis, are just emerging as a hot research field. Objective: This review aims to summarize current knowledge on herbal ncRNAs and their regulatory roles in bioactive compound production. Results and Conclusion: So far, scientists have identified thousands of miRNA candidates from over 50 medicinal plant species and 11794 lncRNAs from Salvia miltiorrhiza, Panax ginseng, and Digitalis purpurea. Among them, more than 30 miRNAs and five lncRNAs have been predicted to regulate bioactive compound production. The regulation may achieve through various regulatory modules and pathways, such as the miR397-LAC module, the miR12112-PPO module, the miR156-SPL module, the miR828-MYB module, the miR858-MYB module, and other siRNA and lncRNA regulatory pathways. Further functional analysis of herbal ncRNAs will provide useful information for quality and quantity improvement of medicinal plants.


2021 ◽  
Vol 30 (9) ◽  
pp. S8-S16
Author(s):  
Eleanor L Stevenson ◽  
Cheng Ching-Yu ◽  
Chang Chia-Hao ◽  
Kevin R McEleny

Male-factor infertility is a common but stigmatised issue, and men often do not receive the emotional support and the information they need. This study sought to understand awareness of male fertility issues compared to female fertility among the UK general male public, and also what were perceived as being the optimum methods for providing support for affected men, emotionally and through information. Men feel that male infertility is not discussed by the public as much as female infertility. Lifestyle issues that affect male fertility are not well understood, and men affected by infertility desire more support, including online, from health professionals and through peer support. Health professionals, including those in public health, could offer evidence-based programmes to reduce stigma and increase public knowledge about infertility, as well as offer emotional support to men with infertility problems.


2021 ◽  
Vol 48 (3) ◽  
pp. 2775-2789
Author(s):  
Ludwig Stenz

AbstractThe 300 bp dimeric repeats digestible by AluI were discovered in 1979. Since then, Alu were involved in the most fundamental epigenetic mechanisms, namely reprogramming, pluripotency, imprinting and mosaicism. These Alu encode a family of retrotransposons transcribed by the RNA Pol III machinery, notably when the cytosines that constitute their sequences are de-methylated. Then, Alu hijack the functions of ORF2 encoded by another transposons named L1 during reverse transcription and integration into new sites. That mechanism functions as a complex genetic parasite able to copy-paste Alu sequences. Doing that, Alu have modified even the size of the human genome, as well as of other primate genomes, during 65 million years of co-evolution. Actually, one germline retro-transposition still occurs each 20 births. Thus, Alu continue to modify our human genome nowadays and were implicated in de novo mutation causing diseases including deletions, duplications and rearrangements. Most recently, retrotransposons were found to trigger neuronal diversity by inducing mosaicism in the brain. Finally, boosted during viral infections, Alu clearly interact with the innate immune system. The purpose of that review is to give a condensed overview of all these major findings that concern the fascinating physiology of Alu from their discovery up to the current knowledge.


Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 109
Author(s):  
Álvaro M. Martins ◽  
Cátia C. Ramos ◽  
Daniela Freitas ◽  
Celso A. Reis

Glycans are major constituents of extracellular vesicles (EVs). Alterations in the glycosylation pathway are a common feature of cancer cells, which gives rise to de novo or increased synthesis of particular glycans. Therefore, glycans and glycoproteins have been widely used in the clinic as both stratification and prognosis cancer biomarkers. Interestingly, several of the known tumor-associated glycans have already been identified in cancer EVs, highlighting EV glycosylation as a potential source of circulating cancer biomarkers. These particles are crucial vehicles of cell–cell communication, being able to transfer molecular information and to modulate the recipient cell behavior. The presence of particular glycoconjugates has been described to be important for EV protein sorting, uptake and organ-tropism. Furthermore, specific EV glycans or glycoproteins have been described to be able to distinguish tumor EVs from benign EVs. In this review, the application of EV glycosylation in the development of novel EV detection and capture methodologies is discussed. In addition, we highlight the potential of EV glycosylation in the clinical setting for both cancer biomarker discovery and EV therapeutic delivery strategies.


2020 ◽  
Vol 401 (6-7) ◽  
pp. 855-876 ◽  
Author(s):  
Roland Lill

AbstractProtein cofactors often are the business ends of proteins, and are either synthesized inside cells or are taken up from the nutrition. A cofactor that strictly needs to be synthesized by cells is the iron-sulfur (Fe/S) cluster. This evolutionary ancient compound performs numerous biochemical functions including electron transfer, catalysis, sulfur mobilization, regulation and protein stabilization. Since the discovery of eukaryotic Fe/S protein biogenesis two decades ago, more than 30 biogenesis factors have been identified in mitochondria and cytosol. They support the synthesis, trafficking and target-specific insertion of Fe/S clusters. In this review, I first summarize what led to the initial discovery of Fe/S protein biogenesis in yeast. I then discuss the function and localization of Fe/S proteins in (non-green) eukaryotes. The major part of the review provides a detailed synopsis of the three major steps of mitochondrial Fe/S protein biogenesis, i.e. the de novo synthesis of a [2Fe-2S] cluster on a scaffold protein, the Hsp70 chaperone-mediated transfer of the cluster and integration into [2Fe-2S] recipient apoproteins, and the reductive fusion of [2Fe-2S] to [4Fe-4S] clusters and their subsequent assembly into target apoproteins. Finally, I summarize the current knowledge of the mechanisms underlying the maturation of cytosolic and nuclear Fe/S proteins.


1978 ◽  
Vol 27 ◽  
pp. 51-56 ◽  
Author(s):  
Fiorella Shabtai ◽  
Shlomo Bichacho ◽  
Isaac Halbrecht

The negative influence of some insecticides on male fertility has been noted. We report our cytogenetic observations on a group of infertile insecticide workers. Increased chromosomal breakage was a constant finding and the Y chromosome was especially damaged. This may account for impaired spermatogenesis. Furthermore, the involvement of heterochromatic chromosomal variants both in the individual susceptibility to the chemically induced damage and in the reproductive fitness is emphasized.


Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 196
Author(s):  
Julie A. Hicks ◽  
Hsiao-Ching Liu

As the chick transitions from embryonic to post-hatching life, its metabolism must quickly undergo a dramatic switch in its major energy source. The chick embryo derives most of its energy from the yolk, a lipid-rich/carbohydrate-poor source. Upon hatching, the chick’s metabolism must then be able to utilize a lipid-poor/carbohydrate-rich source (feed) as its main form of energy. We recently found that a number of hepatically-expressed microRNAs (miRNAs) help facilitate this shift in metabolic processes in the chick liver, the main site of lipogenesis. While adipose tissue was initially thought to mainly serve as a lipid storage site, it is now known to carry many metabolic, endocrine, and immunological functions. Therefore, it would be expected that adipose tissue is also an important factor in the metabolic switch. To that end, we used next generation sequencing (NGS) and real-time quantitative PCR (RT-qPCR) to generate miRNome and transcriptome signatures of the adipose tissue during the transition from late embryonic to early post-hatch development. As adipose tissue is well known to produce inflammatory and other immune factors, we used SPF white leghorns to generate the initial miRNome and transcriptome signatures to minimize complications from external factors (e.g., pathogenic infections) and ensure the identification of bona fide switch-associated miRNAs and transcripts. We then examined their expression signatures in the adipose tissue of broilers (Ross 708). Using E18 embryos as representative of pre-switching metabolism and D3 chicks as a representative of post-switching metabolism, we identified a group of miRNAs which work concordantly to regulate a diverse but interconnected group of developmental, immune and metabolic processes in the adipose tissue during the metabolic switch. Network mapping suggests that during the first days post-hatch, despite the consumption of feed, the chick is still heavily reliant upon adipose tissue lipid stores for energy production, and is not yet efficiently using their new energy source for de novo lipid storage. A number of core master regulatory pathways including, circadian rhythm transcriptional regulation and growth hormone (GH) signaling, likely work in concert with miRNAs to maintain an essential balance between adipogenic, lipolytic, developmental, and immunological processes in the adipose tissue during the metabolic switch.


BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hassan Osman Alhassan Elsaid ◽  
Tarteel Gadkareim ◽  
Tagwa Abobakr ◽  
Eiman Mubarak ◽  
Mehad A. Abdelrhem ◽  
...  

Abstract Background Male factor is the major contributor in roughly half of infertility cases. Genetic factors account for 10–15% of male infertility. Microdeletions of azoospermia factors (AZF) on the Yq region are the second most frequent spermatogenesis disorder among infertile men after Klinefelter syndrome. We detected in our previous study a frequency of 37.5% AZF microdeletions which investigated mainly the AZFb and AZFc. We attempted in this study for the first time to evaluate the frequencies of all AZF sub-regions microdeletions and to analyze reproductive hormonal profiles in idiopathic cases of azoospermic and oligozoospermic men from Sudan. Methods A group of 51 medically fit infertile men were subjected to semen analysis. Four couples have participated in this study as a control group. Semen analysis was performed according to WHO criteria by professionals at Elsir Abu-Elhassan Fertility Centre where samples have been collected. We detected 12 STSs markers of Y chromosome AZF microdeletions using a multiplex polymerase chain reaction. Analysis of reproductive hormone levels including Follicle Stimulating, Luteinizing, and Prolactin hormones was performed using ELISA. Comparisons between outcome groups were performed using Student’s t-test Chi-square test or Fisher’s exact test. Results AZF microdeletion was identified in 16 out of 25 Azoospermic and 14 out of 26 of the Oligozoospermic. Microdeletion in the AZFa region was the most frequent among the 30 patients (N = 11) followed by AZFc, AZFd (N = 4 for each) and AZFb (N = 3). Among the Oligozoospermic participants, the most frequent deletions detected were in the AZFa region (N = 10 out of 14) and was significantly associated with Oligozoospermic phenotype, Fisher's Exact Test (2-sided) p = 0.009. Among the Azoospermic patients, the deletion of the AZFc region was the most frequent (N = 9 out of 16) and was significantly associated with Azoospermia phenotype Fisher's Exact Test p = 0.026. There was a significant difference in Y chromosome microdeletion frequency between the two groups. The hormonal analysis showed that the mean levels of PRL, LH, and FSH in Azoospermic patients were slightly higher than those in oligozoospermic. A weak negative correlation between prolactin higher level and Azoospermic patients was detected. (AZFa r = 0.665 and 0.602, p = 0.000 and 0.0004, AZFb r = 0.636 and 0.409, p = 0.000 and 0.025, and AZFd r = 0.398 and 0.442, p = 0.029 and 0.015). The correlation was positive for AZFa and negative for AZFb and AZFd. Conclusions We concluded in this study that the incidences of microdeletions of the Y chromosome confined to AZF a, b, c and d regions is 58.8% in infertile subjects with 31.4% were Azoospermic and 27.5% were Oligozoospermic. This might provide a piece of evidence that these specified regions of the Y chromosome are essential for controlling spermatogenesis. These findings will be useful for genetic counseling within infertility clinics in Sudan and to adopt appropriate methods for assisted reproduction.


1983 ◽  
Vol 36 (4) ◽  
pp. 333 ◽  
Author(s):  
A RJones

Non-steroidal chemicals that affect male fertility have been known for over 25 years but only one compound, oc-chlorohydrin, possesses most of the attributes of an ideal male contraceptive. In the male rat, for example, continuous daily oral administration of low doses produces an almost immediate and continuous antifertility response that ceases when treatment is withdrawn. Such a dose regime does not interfere with libido, is apparently not toxic and the action is specific towards mature sperm. Furthermore, the action of the compound is species-specific: it is effective in the rat, ram, boar, guinea pig, hamster,rhesus monkey and upon ejaculated human sperm but it is ineffective in the mouse and the rabbit. High doses of oc-chlorohydrin can be neurotoxic, nephrotoxic and, in rats, lead to prolonged or permanent infertility. However, the antifertility response and the toxicity of racemic oc-chlorohydrin may be due, respectively, to the separate enantiomers. No other antifertility chemical has been investigated to such an extent as oc-chlorohydrin; this article reviews the progress that has been achieved with oc-chlorohydrin during the past six years.


Author(s):  
Mary Kathryn Bohn ◽  
Siobhan Wilson ◽  
Alexandra Hall ◽  
Khosrow Adeli

Abstract Objectives The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) has developed an extensive database of reference intervals (RIs) for several biomarkers on various analytical systems. In this study, pediatric RIs were verified for key immunoassays on the Abbott Alinity system based on the analysis of healthy children samples and comparison to comprehensive RIs previously established for Abbott ARCHITECT assays. Methods Analytical performance of Alinity immunoassays was first assessed. Subsequently, 100 serum samples from healthy children recruited with informed consent were analyzed for 16 Alinity immunoassays. The percentage of test results falling within published CALIPER ARCHITECT reference and confidence limits was determined. If ≥ 90% of test results fell within the confidence limits, they were considered verified based on CLSI guidelines. If <90% of test results fell within the confidence limits, additional samples were analyzed and new Alinity RIs were established. Results Of the 16 immunoassays assessed, 13 met the criteria for verification with test results from ≥ 90% of healthy serum samples falling within the published ARCHITECT confidence limits. New CALIPER RIs were established for free thyroxine and prolactin on the Alinity system. Estradiol required special considerations in early life. Conclusions Our data demonstrate excellent concordance between ARCHITECT and Alinity immunoassays, as well as the robustness of previously established CALIPER RIs for most immunoassays, eliminating the need for de novo RI studies for most parameters. Availability of pediatric RIs for immunoassays on the Alinity system will assist clinical laboratories using this new platform and contribute to improved clinical decision-making.


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