PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 8055675

Sperm function and its manipulation for microassisted fertilization.

S Fleming·S Green·J Hall·S Fishel
View original source ↗Export metadata ↓

Abstract

Comprehension of the intricate complexities of sperm function is clearly crucial to the success of attempts to manipulate it for the purposes of assisted conception. This is particularly important when considering various procedures for microassisted fertilization since these bypass critical physiological events that are mandatory for normal fertilization, to varying degrees. Methylxanthine derivatives such as pentoxifylline are useful agents for the management of oligoasthenozoospermic patients. This is particularly so for procedures such as SUZI where adequate motility of spermatozoa injected into the perivitelline space is crucial for fusion with the vitelline membrane to achieve fertilization. The generation of minute concentrations of reactive oxygen species in vitro may prove to be a valuable technique in this respect, in the light of recent evidence for their involvement in capacitation and hyperactivation. Induction of the acrosome reaction by non-invasive, non-toxic agents should markedly improve success rates for microassisted fertilization. Acrosin appears to play a central role in this and, therefore, it would seem prudent to monitor levels of acrosin activity in samples of spermatozoa used in assisted conception procedures. With respect to microassisted fertilization, the potential to select recently acrosome-reacted spermatozoa coated by activated acrosin promises to be a major improvement. Current methods employed for determination of the fertilization potential of spermatozoa are clearly inadequate (Polansky and Lamb, 1988; Aitken, 1990). In fact, the prevailing evidence suggests that no single parameter of sperm function reflects this potential (Zaneveld and Jeyendran, 1988). Therefore, we have both a scientific and a moral responsibility to investigate these processes further. Subsequently, we should be in a position to identify individual gametes with the potential for fertilization and so utilize procedures that result in maximal fertilization rates with minimal risk of polyploidy or abnormality.

Explore related subjects

AutoantibodiesElectroporationFemaleFertilization in VitroHumansIsoantibodiesMaleMicromanipulationSpecimen HandlingSperm TransportSperm-Ovum InteractionsSpermatozoaZona PellucidaJournal ArticleReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

S Fleming, S Green, J Hall, S Fishel. 1994. Sperm function and its manipulation for microassisted fertilization.. https://doi.org/10.1016/s0950-3552(05)80023-9

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2022

Integration of Infant Metabolite, Genetic, and Islet Autoimmunity Signatures to Predict Type 1 Diabetes by Age 6 Years.

CONTEXT: Biomarkers that can accurately predict risk of type 1 diabetes (T1D) in genetically predisposed children can facilitate interventions to delay or prevent the disease. OBJECTIVE: This work aimed to determine if a combination of genetic, immunologic, and metabolic features, measured at infancy, can be used to predict the likelihood that a child will develop T1D by age 6 years. METHODS: Newborns with human leukocyte antigen (HLA) typing were enrolled in the prospective birth cohort of The Environmental Determinants of Diabetes in the Young (TEDDY). TEDDY ascertained children in Finland, Germany, Sweden, and the United States. TEDDY children were either from the general population or from families with T1D with an HLA genotype associated with T1D specific to TEDDY eligibility criteria. From the TEDDY cohort there were 702 children will all data sources measured at ages 3, 6, and 9 months, 11.4% of whom progressed to T1D by age 6 years. The main outcome measure was a diagnosis of T1D as diagnosed by American Diabetes Association criteria. RESULTS: Machine learning-based feature selection yielded classifiers based on disparate demographic, immunologic, genetic, and metabolite features. The accuracy of the model using all available data evaluated by the area under a receiver operating characteristic curve is 0.84. Reducing to only 3- and 9-month measurements did not reduce the area under the curve significantly. Metabolomics had the largest value when evaluating the accuracy at a low false-positive rate. CONCLUSION: The metabolite features identified as important for progression to T1D by age 6 years point to altered sugar metabolism in infancy. Integrating this information with classic risk factors improves prediction of the progression to T1D in early childhood.

Autoantibodies↗
PubMed2022

Heterogeneity of Acetylcholine Receptor Autoantibody-Mediated Complement Activity in Patients With Myasthenia Gravis.

BACKGROUND AND OBJECTIVES: Autoantibodies targeting the acetylcholine receptor (AChR), found in patients with myasthenia gravis (MG), mediate pathology through 3 mechanisms: complement-directed tissue damage, blocking of the acetylcholine binding site, and internalization of the AChR. Clinical assays, used to diagnose and monitor patients, measure only autoantibody binding. Consequently, they are limited in providing association with disease burden, understanding of mechanistic heterogeneity, and monitoring therapeutic response. The objective of this study was to develop a cell-based assay that measures AChR autoantibody-mediated complement membrane attack complex (MAC) formation. METHODS: An HEK293T cell line-modified using CRISPR/Cas9 genome editing to disrupt expression of the complement regulator genes (CD46, CD55, and CD59)-was used to measure AChR autoantibody-mediated MAC formation through flow cytometry. RESULTS: Serum samples (n = 155) from 96 clinically confirmed AChR MG patients, representing a wide range of disease burden and autoantibody titer, were tested along with 32 healthy donor (HD) samples. AChR autoantibodies were detected in 139 of the 155 (89.7%) MG samples through a cell-based assay. Of the 139 AChR-positive samples, autoantibody-mediated MAC formation was detected in 83 (59.7%), whereas MAC formation was undetectable in the HD group or AChR-positive samples with low autoantibody levels. MAC formation was positively associated with autoantibody binding in most patient samples; ratios (mean fluorescence intensity) of MAC formation to AChR autoantibody binding ranged between 0.27 and 48, with a median of 0.79 and an interquartile range of 0.43 (0.58-1.1). However, the distribution of ratios was asymmetric and included extreme values; 16 samples were beyond the 10-90 percentile, with high MAC to low AChR autoantibody binding ratio or the reverse. Correlation between MAC formation and clinical disease scores suggested a modest positive association (rho = 0.34, p = 0.0023), which included a subset of outliers that did not follow this pattern. MAC formation did not associate with exposure to immunotherapy, thymectomy, or MG subtypes defined by age-of-onset. DISCUSSION: A novel assay for evaluating AChR autoantibody-mediated complement activity was developed. A subset of patients that lacks association between MAC formation and autoantibody binding or disease burden was identified. The assay may provide a better understanding of the heterogeneous autoantibody molecular pathology and identify patients expected to benefit from complement inhibitor therapy.

Autoantibodies↗