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Single-center thorough evaluation and targeted treatment of globozoospermic men

PURPOSE: To characterize, by specific biomarkers and nucleic acid sequencing, the structural and genomic sperm characteristics of partial (PG) and complete globozoospermic (CG) men in order to identify the best reproductive treatment. METHODS: We assessed spermatozoa from 14 consenting men ultrastru...

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Autores principales: Cheung, Stephanie, Parrella, Alessandra, Tavares, Danielle, Keating, Derek, Xie, Philip, Rosenwaks, Zev, Palermo, Gianpiero D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417186/
https://www.ncbi.nlm.nih.gov/pubmed/33877510
http://dx.doi.org/10.1007/s10815-021-02191-4
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author Cheung, Stephanie
Parrella, Alessandra
Tavares, Danielle
Keating, Derek
Xie, Philip
Rosenwaks, Zev
Palermo, Gianpiero D.
author_facet Cheung, Stephanie
Parrella, Alessandra
Tavares, Danielle
Keating, Derek
Xie, Philip
Rosenwaks, Zev
Palermo, Gianpiero D.
author_sort Cheung, Stephanie
collection PubMed
description PURPOSE: To characterize, by specific biomarkers and nucleic acid sequencing, the structural and genomic sperm characteristics of partial (PG) and complete globozoospermic (CG) men in order to identify the best reproductive treatment. METHODS: We assessed spermatozoa from 14 consenting men ultrastructurally, as well as for histone content, sperm chromatin integrity, and sperm aneuploidy. Additional genomic, transcriptomic, and proteomic evaluations were carried out to further characterize the CG cohort. The presence of oocyte-activating sperm cytosolic factor (OASCF) was measured by a phospholipase C zeta (PLCζ) immunofluorescence assay. Couples were treated in subsequent cycles either by conventional ICSI or by ICSI with assisted gamete treatment (AGT) using calcium ionophore (Ionomycin, 19657, Sigma-Aldrich, Saint Louis, MO, USA). RESULTS: Ultrastructural assessment confirmed complete acrosome deficiency in all spermatozoa from CG men. Histone content, sperm chromatin integrity, and sperm aneuploidy did not differ significantly between the PG (n = 4) and CG (n = 10) cohorts. PLCζ assessment indicated a positive presence of OASCF in 4 PG couples, who underwent subsequent ICSI cycles that yielded a 36.1% (43/119) fertilization with a 50% (2/4) clinical pregnancy and delivery rate. PLCζ assessment failed to detect OASCF for 8 CG patients who underwent 9 subsequent ICSI cycles with AGT, yielding a remarkable improvement of fertilization (39/97; 40.2%) (P = 0.00001). Embryo implantation (6/21; 28.6%) and clinical pregnancies (5/7; 71.4%) were also enhanced, resulting in 4 deliveries. Gene mutations (DPY19L2, SPATA16, PICK1) were identified in spermatozoa from CG patients. Additionally, CG patients unable to sustain a term pregnancy had gene mutations involved in zygote development (NLRP5) and postnatal development (BSX). CG patients who successfully sustained a pregnancy had a mutation (PIWIL1) related to sperm phenotype. PLCZ1 was both mutated and underexpressed in these CG patients, regardless of reproductive outcome. CONCLUSIONS: Sperm bioassays and genomic studies can be used to characterize this gamete’s capacity to support embryonic development and to tailor treatments maximizing reproductive outcome. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-021-02191-4.
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spelling pubmed-84171862021-09-22 Single-center thorough evaluation and targeted treatment of globozoospermic men Cheung, Stephanie Parrella, Alessandra Tavares, Danielle Keating, Derek Xie, Philip Rosenwaks, Zev Palermo, Gianpiero D. J Assist Reprod Genet Reproductive Physiology and Disease PURPOSE: To characterize, by specific biomarkers and nucleic acid sequencing, the structural and genomic sperm characteristics of partial (PG) and complete globozoospermic (CG) men in order to identify the best reproductive treatment. METHODS: We assessed spermatozoa from 14 consenting men ultrastructurally, as well as for histone content, sperm chromatin integrity, and sperm aneuploidy. Additional genomic, transcriptomic, and proteomic evaluations were carried out to further characterize the CG cohort. The presence of oocyte-activating sperm cytosolic factor (OASCF) was measured by a phospholipase C zeta (PLCζ) immunofluorescence assay. Couples were treated in subsequent cycles either by conventional ICSI or by ICSI with assisted gamete treatment (AGT) using calcium ionophore (Ionomycin, 19657, Sigma-Aldrich, Saint Louis, MO, USA). RESULTS: Ultrastructural assessment confirmed complete acrosome deficiency in all spermatozoa from CG men. Histone content, sperm chromatin integrity, and sperm aneuploidy did not differ significantly between the PG (n = 4) and CG (n = 10) cohorts. PLCζ assessment indicated a positive presence of OASCF in 4 PG couples, who underwent subsequent ICSI cycles that yielded a 36.1% (43/119) fertilization with a 50% (2/4) clinical pregnancy and delivery rate. PLCζ assessment failed to detect OASCF for 8 CG patients who underwent 9 subsequent ICSI cycles with AGT, yielding a remarkable improvement of fertilization (39/97; 40.2%) (P = 0.00001). Embryo implantation (6/21; 28.6%) and clinical pregnancies (5/7; 71.4%) were also enhanced, resulting in 4 deliveries. Gene mutations (DPY19L2, SPATA16, PICK1) were identified in spermatozoa from CG patients. Additionally, CG patients unable to sustain a term pregnancy had gene mutations involved in zygote development (NLRP5) and postnatal development (BSX). CG patients who successfully sustained a pregnancy had a mutation (PIWIL1) related to sperm phenotype. PLCZ1 was both mutated and underexpressed in these CG patients, regardless of reproductive outcome. CONCLUSIONS: Sperm bioassays and genomic studies can be used to characterize this gamete’s capacity to support embryonic development and to tailor treatments maximizing reproductive outcome. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-021-02191-4. Springer US 2021-04-20 2021-08 /pmc/articles/PMC8417186/ /pubmed/33877510 http://dx.doi.org/10.1007/s10815-021-02191-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Reproductive Physiology and Disease
Cheung, Stephanie
Parrella, Alessandra
Tavares, Danielle
Keating, Derek
Xie, Philip
Rosenwaks, Zev
Palermo, Gianpiero D.
Single-center thorough evaluation and targeted treatment of globozoospermic men
title Single-center thorough evaluation and targeted treatment of globozoospermic men
title_full Single-center thorough evaluation and targeted treatment of globozoospermic men
title_fullStr Single-center thorough evaluation and targeted treatment of globozoospermic men
title_full_unstemmed Single-center thorough evaluation and targeted treatment of globozoospermic men
title_short Single-center thorough evaluation and targeted treatment of globozoospermic men
title_sort single-center thorough evaluation and targeted treatment of globozoospermic men
topic Reproductive Physiology and Disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417186/
https://www.ncbi.nlm.nih.gov/pubmed/33877510
http://dx.doi.org/10.1007/s10815-021-02191-4
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