Absence of sperm RNA elements correlates with idiopathic male infertility

Jodar, Meritxell; Sendler, Edward; Moskovtsev, Sergey I.; Librach, Clifford L.; Goodrich, Robert; Swanson, Sonja A.; Hauser, Russ; Diamond, Michael P.; Krawetz, Stephen A.

doi:10.1126/scitranslmed.aab1287

Cited by 138 publications

(104 citation statements)

References 43 publications

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“…Many spermatozoa transcripts may represent non-or incompletely destructed and retained transcripts from round and elongating spermatids. However, even if only a small fraction of the 16,900 transcripts encode functional RNAs, it becomes more and more evident that these transcripts (respectively, their corresponding genes) have evolutionary [109] and fertility-related [110] relevance. That species-spe-cific differences also occur in the spermatozoa transcriptome is nicely reflected by the fact that protamine expression is different in man and rat.…”

Section: The Haploid Phase Of the Germlinementioning

confidence: 99%

Characteristic Features of Male Germline Development in Primates

Behr¹

2017

Genetics of Human Infertility

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The germline is constituted by all cells that have the potential to transmit their genetic information to the next generation. The germline can be considered as a defined sequence of genetic, cellular, and developmental processes recurring in each generation in order to ensure the continuity of a species-specific reproduction program. Although basic mechanisms of germline development in mammals are highly conserved, relatively slight yet relevant modifications of germline development evolved in different groups of mammals to adapt the entire process to the specific requirements of and conditions in each species. This review highlights selected aspects that illustrate germline adaptations and characteristics in primates mainly in comparison to the mouse, which is the best investigated mammalian model organism in reproductive biology. The germline is constituted by all cells that have the potential to submit their genetic information to the next generation. The cycle of the germline in mammals is characterized by the recurring sequence of (1) fertilization, i.e., fusion of 2 haploid gametes, resulting in (2) a diploid phase of early embryonic development, which leads to (3) the specification and separation of germ cells (primordial germ cells; PGCs) from somatic cells, followed by (4) several rounds of mitotic divisions of the germ cells. Then (5) the germ cells enter meiosis, i.e., the genetic reduction division, resulting in (6) haploid cells forming gametes again. Fusion of the haploid male and the female gametes completes the cycle of the germline and begins the next generation ( Fig. 1 ). This sequence of events occurs in all mammals. However, different species exhibit specific adaptations and characteristics of 1 or more phases of the cycle of the germline. Remarkably, the cycle of the germline is an extremely robust process that works "endlessly". On the other hand, certain dynamics of the germline is essential for evolution since only modifications of the germline cells can lead to (genetically or epigenetically) inherited traits possibly resulting in better-adapted offspring and, hence, supporting species diversion. In light of these conflicting goals, namely germline stability and genome dynamics, some selected characteristic features of male germ cell development in pri- A new generation is initiated by the formation of a zygote, i.e., the fertilized oocyte. In the morula-stage embryo, the individual cells (blastomeres) are not yet specified. They are all potential progenitor cells of the prospective germ cells. The blastocyst consists of 2 clearly distinguishable cell populations: the inner cell mass cells (highlighted by red arrows) and the outer cell layer, i.e., the trophoblast. The germ cells develop from the inner cell mass cells. In the implantation embryo the first specified germ cells, called PGCs, occur. In the somite-stage embryos they are frequently located in the epithelium of the developing hind gut (red arrows). In the fetus, most PGCs have entered the forming gonad. The magnifie...

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Section: The Haploid Phase Of the Germlinementioning

confidence: 99%

Characteristic Features of Male Germline Development in Primates

Behr¹

2017

Genetics of Human Infertility

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“…An ever-increasing number of research groups are utilizing novel technologies to investigate each of these “-omics” areas in an effort to discover novel male fertility biomarkers. Transcriptomics, for example, has had promising results from several groups, demonstrating RNA profiles of “required elements” for natural fertility 15, 16 .…”

Section: Recent Advancesmentioning

confidence: 99%

Recent advances in understanding & managing male infertility

Bieniek

2016

F1000Res

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Male infertility remains a struggle to definitively diagnose and treat with many men labelled as “idiopathic infertility” and eventually requiring assisted reproductive techniques. Along those lines, research groups are continuing to explore current social and environmental factors, including the obesity epidemic, and their effects on male fertility potential. Novel biomarkers of natural fertility status and azoospermia etiology have additionally seen recent attention with ACRV1 and TEX101/ECM1 assays either currently or soon to be commercially available. Despite these advancements, however, medical treatment options have seen little progress. Though surgical therapies have similarly seen little transformation, groups are exploring the use of testicular sperm for couples with elevated sperm DNA fragmentation and either planned or previously failed IVF/ICSI. Concerted collaborative efforts will be needed as we move forward to better understand the challenges men face when struggling to conceive.

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“…A strong expression of prostate and seminal vesicle markers TGM4/MSMB/ SEMG1/SEMG2 is observable in all samples, and Cluster 2 (yellow) also contains the epithelial and leukocyte markers CDH1 and IL8, respectively. Samples were clustered on the basis of all 278,605 features, which resulted in two clearly separable groups ("Cluster") that do not correlate with the original grouping ("Group") defined in (1).…”

Section: Supplementary Materialsmentioning

confidence: 99%

“…Although swim-up enriches for the most motile subpopulation and delivers rather low sperm numbers, the latter two have been used in gene expression studies of S. A. Krawetz and his group. Some initial microarray studies used somatic cell lysis (9), whereas recent RNA sequencing studies (2-5), including that of Jodar et al (1), are based on the 50% density gradient centrifugation protocol described in (7).…”

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confidence: 99%

Comment on “Absence of sperm RNA elements correlates with idiopathic male infertility”

Cappallo-Obermann

Spiess

2016

Sci. Transl. Med.

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The spermatozoal population used for a recent RNA sequencing study may have been contaminated by somatic cell types because of an inefficient sperm purification procedure.In a recent article (1), Jodar and co-workers describe a next-generation sequencing-based analysis of spermatozoal RNAs and their correlation to the outcome of natural conception and assisted reproduction techniques. The same group (S. A. Krawetz) has previously published several gene expression studies (2-5) on human spermatozoa that are based on RNA sequencing of purified sperm populations. Sperm purification is a mandatory procedure because ejaculates are routinely contaminated with so-called "round cells," mostly somatic cells such as leukocytes, macrophages, and epithelial cells of the genital tract but also nonsomatic and less differentiated germ cells (spermatocytes and round spermatids). In contrast to sperm concentration, morphology, and motility, no reference values for round cells exist, but the World Health Organization states a consensus value of 1 × 10 6 /ml for peroxidase-positive leukocytes (6). To obtain an overview on the proportion of round cells in ejaculates of men enrolled in an assisted reproduction program at our clinic (Department of Andrology, University Hospital HamburgEppendorf), we have compiled round cell concentrations from 100 patients seen in the year 2014 ( fig. S1). More than 30% of these men exhibited round cell concentrations that were well in excess of 5 × 10 6

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Absence of sperm RNA elements correlates with idiopathic male infertility

Cited by 138 publications

References 43 publications

Characteristic Features of Male Germline Development in Primates

Characteristic Features of Male Germline Development in Primates

Recent advances in understanding & managing male infertility

Comment on “Absence of sperm RNA elements correlates with idiopathic male infertility”

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