Publications by authors named "Douglas Carrell"

Context: Dyslipidemia is common, and resultant endothelial dysfunction may impact reproductive outcomes. No prospective study has examined the effect of preconception lipid parameters in both female and male partners or their interaction on live birth.

Objective: To determine whether live birth is associated with preconception lipids in both partners by planned fertility treatment.

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Background: Single-cell RNA-seq (scRNA-Seq) has been widely adopted to study gene expression of the human testis. Several datasets of scRNA-Seq from human testis have been generated from different groups processed with different informatics pipelines. An integrated atlas of scRNA-Seq expression constructed from multiple donors, developmental ages, and fertility states would be widely useful for the testis research community.

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Non-obstructive azoospermia (NOA) is the most severe form of male infertility and typically incurable. Defining the genetic basis of NOA has proven challenging, and the most advanced classification of NOA subforms is not based on genetics, but simple description of testis histology. In this study, we exome-sequenced over 1000 clinically diagnosed NOA cases and identified a plausible recessive Mendelian cause in 20%.

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Objective: To examine whether semen parameters are associated with live birth among couples seeking infertility treatment after accounting for semen parameter variability.

Design: Folic Acid and Zinc Supplementation Trial (FAZST) prospective cohort.

Setting: Four US reproductive endocrinology and infertility care study centers, 2013-2017.

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Article Synopsis
  • Biomedical science is improving in transparency and reproducibility, which is crucial for research involving semen analysis.
  • Two key documents have been released: the WHO Laboratory Manual and the International Standard ISO 23162:2021, both focusing on semen examination protocols.
  • It is recommended that authors adhere to these guidelines when publishing their studies, ideally using a provided checklist for proper compliance.
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Objective: To determine if 6-month folic acid (5 mg) and zinc (30 mg) supplementation impacts sperm DNA methylation patterns.

Design: A multicenter, double-blind, block randomized, placebo-controlled trial titled "The Folic Acid and Zinc Supplementation Trial (FAZST)."

Setting: Infertility care centers.

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Klinefelter syndrome (KS), also known as 47, XXY, is characterized by a distinct set of physiological abnormalities, commonly including infertility. The molecular basis for Klinefelter-related infertility is still unclear, largely because of the cellular complexity of the testis and the intricate endocrine and paracrine signaling that regulates spermatogenesis. Here, we demonstrate an analysis framework for dissecting human testis pathology that uses comparative analysis of single-cell RNA-sequencing data from the biopsies of 12 human donors.

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Background: Despite increasing evidence that particulate air pollution has adverse effects on human semen quality, few studies examine the impact of air pollution on clinically relevant thresholds used to diagnose male fertility problems. Furthermore, exposure is often assessed using average air pollution levels in a geographic area rather than individualized estimates. Finally, physiologically-informed exposure windows are inconsistent.

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Article Synopsis
  • High-throughput RNA sequencing has improved the discovery of small non-coding RNAs (sncRNAs), but current methods have biases due to RNA modifications that hinder detection.
  • The new PANDORA-seq technique removes these modifications, allowing for the identification of previously undetected modified sncRNAs like transfer RNA-derived small RNAs (tsRNAs) and ribosomal RNA-derived small RNAs (rsRNAs) with tissue-specific and cell-specific expressions.
  • By using PANDORA-seq, researchers discovered complex patterns of microRNA, tsRNA, and rsRNA changes during the process of reprogramming cells, indicating that specific tsRNAs and rsRNAs may play critical roles in cellular translation and lineage differentiation.
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Non-obstructive azoospermia (NOA), the lack of spermatozoa in semen due to impaired spermatogenesis affects nearly 1% of men. In about half of cases, an underlying cause for NOA cannot be identified. This study aimed to identify novel variants associated with idiopathic NOA.

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Background: Many environmental and lifestyle factors have been implicated in the decline of sperm quality, with diet being one of the most plausible factors identified in recent years. Moreover, several studies have reported a close association between the alteration of specific sperm DNA methylation signatures and semen quality.

Objectives: To evaluate the effect of tree nut consumption on sperm DNA methylation patterns in healthy individuals reporting eating a Western-style diet.

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Male aging and obesity have both been shown to contribute to declines in fertility in men. Recent work in aging has shown consistent epigenetic changes to sperm as a man ages. In fact, our lab has built a tool that utilizes DNA methylation signatures from sperm to effectively predict an individual's age.

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It is well-established that testicular spermatozoa are immature and acquire motility and fertilization capabilities during transit throughout the epididymis. The epididymis is a duct-like organ that connects the testis to the vas deferens and is comprised of four anatomical regions: the initial segment, caput, corpus, and cauda. Sperm maturation occurs during epididymal transit by the interaction of sperm cells with the unique luminal environment of each epididymal region.

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Purpose: Azoospermia affects 1% of men and it can be the consequence of spermatogenic maturation arrest (MA). Although the etiology of MA is likely to be of genetic origin, only 13 genes have been reported as recurrent potential causes of MA.

Methods: Exome sequencing in 147 selected MA patients (discovery cohort and two validation cohorts).

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Objective: To study the global DNA methylation pattern in spermatozoa of patients with varicocele as well as investigate their semen quality.

Design: Prospective observational case-control study.

Setting: University-affiliated hospital.

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The present updated systematic review and meta-analysis aims to summarize the evidence from published studies with low risk for any important bias (based on methodological quality assessment) investigating the potential associations of adiposity with sperm quality and reproductive hormones. We conducted a systematic search of the literature published in MEDLINE-PubMed and EMBASE through June 2019. Based on the criteria in our review, 169 eligible publications were used for data abstraction.

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Paternal cigarette smoke (CS) exposure is associated with increased risk of behavioral disorders and cancer in offspring, but the mechanism has not been identified. Here we use mouse models to investigate mechanisms and impacts of paternal CS exposure. We demonstrate that CS exposure induces sperm DNAme changes that are partially corrected within 28 days of removal from CS exposure.

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Research is needed to understand the presence of the SARS-CoV-2 virus in semen, sexual transmissibility, and impact on sperm quality. Several studies have examined men recovering from COVID-19, but large-scale community-based testing is needed to ascertain the effects on the male reproductive tract, and the potential for prolonged transmission.

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This was a cohort study of in vitro fertilization (IVF) subjects at the University of Utah, Salt Lake City (UT, USA) utilizing partner sperm. Cycles where both the hamster egg penetration test (HEPT) and semen analysis were performed within 2 years prior to IVF cycles were stratified into four groups based on a normal or an abnormal HEPT and morphology. The mean conventional and intracytoplasmic sperm injection (ICSI) fertilization rates were calculated in each group.

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Objectives: To demonstrate a novel prototype microfluidic system for rapid isolation of sperm from real and simulated microdissection testicular sperm extraction samples.

Methods: The novel microfluidic system was tested using minced testicular biopsies from patients with nonobstructive azoospermia. The samples were split into 2 portions, conventional processing vs microfluidic.

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The human testis undergoes dramatic developmental and structural changes during puberty, including proliferation and maturation of somatic niche cells, and the onset of spermatogenesis. To characterize this understudied process, we profiled and analyzed single-cell transcriptomes of ∼10,000 testicular cells from four boys spanning puberty and compared them to those of infants and adults. During puberty, undifferentiated spermatogonia sequentially expand and differentiate prior to the initiation of gametogenesis.

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