A comprehensive analysis of spermatozoal RNA elements in idiopathic infertile males undergoing fertility treatment.

Current approaches to diagnosing male infertility inadequately assess the complexity of the male gamete. Beyond the paternal haploid genome, spermatozoa also deliver coding and non-coding RNAs to the oocyte. While sperm-borne RNAs have demonstrated potential involvement in embryo development, the underlying mechanisms remain unclear.

Germ Cell-Specific Proteins AKAP4 and ASPX Facilitate Identification of Rare Spermatozoa in Non-Obstructive Azoospermia.

Non-obstructive azoospermia (NOA), the most severe form of male infertility, could be treated with intracytoplasmic sperm injection, providing spermatozoa were retrieved with the microdissection testicular sperm extraction (mTESE). We hypothesized that testis-specific and germ cell-specific proteins would facilitate flow cytometry-assisted identification of rare spermatozoa in semen cell pellets of NOA patients, thus enabling non-invasive diagnostics prior to mTESE. Data mining, targeted proteomics, and immunofluorescent microscopy identified and verified a panel of highly testis-specific proteins expressed at the continuum of germ cell differentiation.

Assessing spermatozoal small ribonucleic acids and their relationship to blastocyst development in idiopathic infertile males.

Clinical testing strategies for diagnosing male factor infertility are limited. A deeper analysis of spermatozoa-derived factors could potentially diagnose some cases of 'unexplained infertility'. Spermatozoa carry a rich and dynamic profile of small RNAs, which have demonstrated potential developmental importance and association with fertility status.

Staining-free, Automated Sperm Analysis for In Vitro Fertilization Lab Use.

Purpose: Computer-aided sperm analysis is typically used in andrology labs, not in in vitro fertilization labs, which requires staining for sperm morphology measurement. In in vitro fertilization labs, sperm analysis still relies on manual observation and suffers from subjectivity and inconsistency. We developed a system for automated measurement of sperm concentration, motility, and morphology without the need for sperm staining.

Whole-genome sequencing of H3K4me3 and DNA methylation in human sperm reveals regions of overlap linked to fertility and development.

The paternal environment has been linked to infertility and negative outcomes. Such effects may be transmitted via sperm through histone modifications. To date, in-depth profiling of the sperm chromatin in men has been limited.

Advances in sperm analysis: techniques, discoveries and applications.

Infertility affects one in six couples worldwide, and fertility continues to deteriorate globally, partly owing to a decline in semen quality. Sperm analysis has a central role in diagnosing and treating male factor infertility. Many emerging techniques, such as digital holography, super-resolution microscopy and next-generation sequencing, have been developed that enable improved analysis of sperm motility, morphology and genetics to help overcome limitations in accuracy and consistency, and improve sperm selection for infertility treatment.

Is there an association between paternal age and aneuploidy? Evidence from young donor oocyte-derived embryos: a systematic review and individual patient data meta-analysis.

Background: Delayed parenthood, by both women and men, has become more common in developed countries. The adverse effect of advanced maternal age on embryo aneuploidy and reproductive outcomes is well known. However, whether there is an association between paternal age (PA) and embryonic chromosomal aberrations remains controversial.

What human sperm RNA-Seq tells us about the microbiome.

Purpose: The study was designed to assess the capacity of human sperm RNA-seq data to gauge the diversity of the associated microbiome within the ejaculate.

Methods: Semen samples were collected, and semen parameters evaluated at time of collection. Sperm RNA was isolated and subjected to RNA-seq.

Customized MethylC-Capture Sequencing to Evaluate Variation in the Human Sperm DNA Methylome Representative of Altered Folate Metabolism.

Background: The sperm DNA methylation landscape is unique and critical for offspring health. If gamete-derived DNA methylation escapes reprograming in early embryos, epigenetic defects in sperm may be transmitted to the next generation. Current techniques to assess sperm DNA methylation show bias toward CpG-dense regions and do not target areas of dynamic methylation, those predicted to be environmentally sensitive and tunable regulatory elements.

Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility.

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo.

Automated Non-Invasive Measurement of Single Sperm's Motility and Morphology.

Measuring cell motility and morphology is important for revealing their functional characteristics. This paper presents automation techniques that enable automated, non-invasive measurement of motility and morphology parameters of single sperm. Compared to the status quo of qualitative estimation of single sperm's motility and morphology manually, the automation techniques provide quantitative data for embryologists to select a single sperm for intracytoplasmic sperm injection.

Robotic Immobilization of Motile Sperm for Clinical Intracytoplasmic Sperm Injection.

Objective: In clinical intracytoplasmic sperm injection (ICSI), a motile sperm must be immobilized before insertion into an oocyte. This paper aims to develop a robotic system for automated tracking, orientation control, and immobilization of motile sperms for clinical ICSI applications.

Methods: We adapt the probabilistic data association filter by adding sperm head orientation into state variables for robustly tracking the sperm head and estimating sperm tail positions under interfering conditions.

Genomic fragmentation and extrachromosomal telomeric repeats impact assessment of telomere length in human spermatozoa: quantitative experiments and systematic review.

Study Question: Can differences in DNA isolation alter assessment of sperm telomere length (spTL) and do they account for conflicting results in the literature on spTL and male fertility?

Summary Answer: DNA isolation methods preferentially include or exclude short, extrachromosomal (EC) telomere-specific sequences that alter spTL measurements, and are responsible for a proportion of the disparity observed between investigations.

What Is Known Already: The relationship between spTL and male fertility has become an active area of research. The results across investigations, however, have been discordant, generating a need to critically evaluate the existing body of knowledge to guide future investigations.

In vitro generation of Sertoli-like and haploid spermatid-like cells from human umbilical cord perivascular cells.

Background: First trimester (FTM) and term human umbilical cord-derived perivascular cells (HUCPVCs), which are rich sources of mesenchymal stem cells (MSCs), can give rise to Sertoli cell (SC)-like as well as haploid germ cell (GC)-like cells in vitro using culture conditions that recapitulate the testicular niche. Gamete-like cells have been produced ex vivo using pluripotent stem cells as well as MSCs. However, the production of functional gametes from human stem cells has yet to be achieved.

Response to Comment on "Absence of sperm RNA elements correlates with idiopathic male infertility".

RNAs from other cell types have minimal impact on male fecundity-associated sperm RNA elements.

Absence of sperm RNA elements correlates with idiopathic male infertility.

Semen parameters are typically used to diagnose male infertility and specify clinical interventions. In idiopathic infertile couples, an unknown male factor could be the cause of infertility even when the semen parameters are normal. Next-generation sequencing of spermatozoal RNAs can provide an objective measure of the paternal contribution and may help guide the care of these couples.

Chromatin and extracellular vesicle associated sperm RNAs.

A diverse pool of RNAs remain encapsulated within the transcriptionally silent spermatozoon despite the dramatic reduction in cellular and nuclear volume following cytoplasm/nucleoplasm expulsion. The impact of this pronounced restructuring on the distribution of transcripts inside the sperm essentially remains unknown. To define their compartmentalization, total RNA >100 nt was extracted from sonicated (SS) mouse spermatozoa and detergent demembranated sucrose gradient fractionated (Cs/Tx) sperm heads.

Assisted reproduction involving gestational surrogacy: an analysis of the medical, psychosocial and legal issues: experience from a large surrogacy program.

Study Question: What are the medical, psychosocial and legal aspects of gestational surrogacy (GS), including pregnancy outcomes and complications, in a large series?

Summary Answer: Meticulous multidisciplinary teamwork, involving medical, legal and psychosocial input for both the intended parent(s) (IP) and the gestational carrier (GC), is critical to achieve a successful GS program.

What Is Known Already: Small case series have described pregnancy rates of 17-50% for GS. There are no large case series and the medical, legal and psychological aspects of GS have not been addressed in most of these studies.

Vitrification of a small number of spermatozoa in normozoospermic and severely oligozoospermic samples.

Despite broad utilization of sperm cryopreservation, little progress has been made to modify freezing protocols or to improve rates of sperm survival. Vitrification is an alternative method for freezing human spermatozoa without toxic permeable cryoprotectants (CPAs). The purpose of our study was to optimize the vitrification and post thaw recovery of a small number of spermatozoa using only nonpermeating CPAs in a closed straw system in normozoospermic and severely oligozoospermic samples.

Sperm-derived WW domain-binding protein, PAWP, elicits calcium oscillations and oocyte activation in humans and mice.

Mammalian zygotic development is initiated by sperm-mediated intracellular calcium oscillations, followed by activation of metaphase II-arrested oocytes. Sperm postacrosomal WW binding protein (PAWP) fulfils the criteria set for an oocyte-activating factor by inducing oocyte activation and being stored in the perinuclear theca, the sperm compartment whose content is first released into oocyte cytoplasm during fertilization. However, proof that PAWP initiates mammalian zygotic development relies on demonstration that it acts upstream of oocyte calcium oscillations.

Sperm content of postacrosomal WW binding protein is related to fertilization outcomes in patients undergoing assisted reproductive technology.

Objective: To determine the levels of postacrosomal WW binding protein (PAWP) in the spermatozoa of men that were used clinically for intracytoplasmic sperm injection (ICSI) and to correlate them with infertility treatment outcomes.

Design: Prospective clinical and laboratory study.

Setting: University-based laboratory and infertility clinic.