TMT-Based Proteomic Analysis of Human Spermatozoa from Unexplained Recurrent Miscarriage Patients before and after Oral Antioxidant Treatment

Fernández-Encinas, Alba; Ribas-Maynou, Jordi; García-Peiró, Agustín; Garcia-Segura, Sergio; Martínez-Pasarell, O.; Navarro, J.; Oliver-Bonet, María; Benet, Jordi

doi:10.3390/biomedicines10082014

Cited by 5 publications

(2 citation statements)

References 62 publications

(74 reference statements)

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“…Antioxidant treatment can result in DNA remodeling in the men of couples with RPL, which may be an indirect sign that improvement of the fragmentation could reduce the miscarriage risk [ 73 ]. Miscarriage risk has been chiefly evaluated as an adverse event, not an infertility endpoint.…”

Section: Resultsmentioning

confidence: 99%

Recurrent miscarriage and male factor infertility: diagnostic and therapeutic implications. A narrative review.

2023

Cent European J Urol

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Introduction Recurrent miscarriage is defined as 2 or more failed clinical pregnancies, typically known as repeated pregnancy loss, occurring before 20 gestational weeks, and further categorized into primary and secondary types. It represents a common and distressing condition to deal with in the field of reproductive medicine, usually affecting <5% of couples, with up to 50% of cases lacking a clearly defined aetiology. The epidemiology also varies depending on maternal age. Remarkably, the situation significantly afflicts expecting parents, whereas maternal factors, such as age and previous pregnancy loss rate, are commonly reported as risk factors. Although previously underestimated, existing evidence suggests the male factor is a possible cause of recurrent pregnancy loss. Material and methods A non-systematic literature review was conducted in the PubMed and Scopus databases for articles written in English investigating the possible association of the male factor in recurrent pregnancy loss. The eligible studies were synthesized in a narrative review format upon discussion and consensus among the authors after being previously independently assessed and selected. Results Lifestyle, obesity, genetic predisposition, chromosomal anomalies, endocrine dysfunction, anatomical abnormalities, immunological factors, infections, and oxidative stress can result in poor embryo development and recurrent miscarriage. Although professional organizations currently recognize male gender as a possible risk factor, specific recommendations on the diagnostic and therapeutic field are still lacking, and the condition necessitates a high level of suspicion and case-by-case management. Conclusions In this review, we delve deeper into the contribution of the male factor in the concept of recurrent miscarriage.

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Section: Resultsmentioning

confidence: 99%

Recurrent miscarriage and male factor infertility: diagnostic and therapeutic implications. A narrative review.

2023

Cent European J Urol

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“…Recurrent spontaneous abortion (RSA), is defined as three or more consecutive pregnancy losses before the fetal weight of 500 g or lower. [ 1 ] This criterion was changed internationally to two or more consecutive spontaneous abortions before 20 weeks of gestation. [ 2 ] The incidence of RSA is 5% of all pregnancies in China and abroad.…”

Section: Introductionmentioning

confidence: 99%

Correlation of TGF-β signaling pathway gene polymorphisms with unexplained recurrent spontaneous abortion

Xue,

Jiang,

Gao

et al. 2023

Medicine

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Background: The association of key genes in the transforming growth factor-β (TGF-β) signaling pathway and their gene polymorphisms with unexplained recurrent spontaneous abortion (URSA) is unclear. Objective: To investigate the association of gene polymorphisms related to the TGF-β signaling pathway in URSA women. Methods: The study population consisted of 80 women with URSA and 90 normal control women, of which 10 women with URSA and 10 normal control women underwent high-throughput sequencing to select loci, and the remaining 70 women with URSA and 80 normal control women underwent flight mass spectrometry experiments to verify gene loci polymorphism. A total of 7 polymorphic loci in interleukin-6 (IL-6), TGF-β1, TNF-α, SMAD1, and TNFRSF4 genes were screened by high-throughput sequencing combined with a review of databases. An SNP flight mass spectrometer (Mass ARRAY detection system) was applied to detect the polymorphisms and their frequencies in 70 women with URSA and 80 normal control women at the 7 gene loci. Results: Among the 7 loci of IL-6, TGF-β1, TNF-α, SMAD1, and TNFRSF4 genes, 2 loci were found to have significantly different allele and genotype frequency distributions between the 70 URSA and 80 normal controls, one was the IL-6 gene -174G/C locus (rs1800795), the risk of disease was 2.636 and 3.231 times higher in individuals carrying the C allele and CC genotype than in those carrying the G allele and GG genotype, respectively; the other was the TGF-β1 gene -509T/C locus (rs1800469), and the risk of disease was 1.959 and 3.609 times higher in individuals carrying the T allele and TT genotype than in those carrying the C allele and CC genotype, respectively. The remaining 5 genetic loci have no statistically significant. Conclusion: IL-6 gene -174G/C locus (rs1800795) genotype CC and allele C may be the causative factor of URSA, TGF-β1 gene -509T/C locus (rs1800469) genotype TT and allele T may be the causative factor of URSA, and polymorphisms of the 2 loci may be associated with URSA.

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Perspective in the Mechanisms for Repairing Sperm DNA Damage

Li,

Wang,

zou

et al. 2024

Reprod. Sci.

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DNA damage in spermatozoa is a major cause of male infertility. It is also associated with adverse reproductive outcomes (including reduced fertilization rates, embryo quality and pregnancy rates, and higher rates of spontaneous miscarriage). The damage to sperm DNA occurs during the production and maturation of spermatozoa, as well as during their transit through the male reproductive tract. DNA damage repair typically occurs during spermatogenesis, oocytes after fertilization, and early embryonic development stages. The known mechanisms of sperm DNA repair mainly include nucleotide excision repair (NER), base excision repair (BER), mismatch repair (MMR), and double-strand break repair (DSBR). The most severe type of sperm DNA damage is double-strand break, and it will be repaired by DSBR, including homologous recombination (HR), classical non-homologous end joining (cNHEJ), alternative end joining (aEJ), and single-strand annealing (SSA). However, the precise mechanisms of DNA repair in spermatozoa remain incompletely understood. DNA repair-associated proteins are of great value in the repair of sperm DNA. Several repair-related proteins have been identified as playing critical roles in condensing chromatin, regulating transcription, repairing DNA damage, and regulating the cell cycle. It is noteworthy that XRCC4-like factor (XLF) and paralog of XRCC4 and XLF (PAXX) -mediated dimerization promote the processing of populated ends for cNHEJ repair, which suggests that XLF and PAXX have potential value in the mechanism of sperm DNA repair. This review summarizes the classic and potential repair mechanisms of sperm DNA damage, aiming to provide a perspective for further research on DNA damage repair mechanisms.

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TMT-Based Proteomic Analysis of Human Spermatozoa from Unexplained Recurrent Miscarriage Patients before and after Oral Antioxidant Treatment

Cited by 5 publications

References 62 publications

Recurrent miscarriage and male factor infertility: diagnostic and therapeutic implications. A narrative review.

Recurrent miscarriage and male factor infertility: diagnostic and therapeutic implications. A narrative review.

Correlation of TGF-β signaling pathway gene polymorphisms with unexplained recurrent spontaneous abortion

Perspective in the Mechanisms for Repairing Sperm DNA Damage

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