Cellular and Molecular Mechanisms of In Vivo and In Vitro SARS-CoV-2 Infection: A Lesson from Human Sperm

Luddi, Alice; Luongo, Francesca Paola; Dragoni, Filippo; Fiaschi, Lia; Vicenti, Ilaria; Lupetti, Pietro; Gentile, Mariangela; Paccagnini, Eugenio; Haxhiu, Alesandro; Ponchia, Rosetta; Governini, Laura; Zazzi, Maurizio; Piomboni, Paola

doi:10.3390/cells11172631

Cited by 7 publications

(6 citation statements)

References 39 publications

(38 reference statements)

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“…If IgA and IgG recognize the SARS-CoV-2 receptor Angiotensin-converting enzyme-2, this can explain the attachment of IgA/IgG-ASA to the tail of spermatozoa, because the receptor is also located on the sperm tail. 26 , 27 Conversely, harmful sIgG-N in blood only significantly correlated with higher DFI. Similarly, early in the pandemic it became clear that our immune system can produce antibodies that are protective or harmful.…”

Section: Discussionmentioning

confidence: 91%

SARS-CoV-2 infection reduces quality of sperm parameters: prospective one year follow-up study in 93 patients

Depuydt¹,

Bosmans²,

Jonckheere³

et al. 2023

eBioMedicine

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Section: Discussionmentioning

confidence: 91%

SARS-CoV-2 infection reduces quality of sperm parameters: prospective one year follow-up study in 93 patients

Depuydt¹,

Bosmans²,

Jonckheere³

et al. 2023

eBioMedicine

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“…Immunofluorescence on the spermatozoa was performed after fixation with 4% PFA for 25 min as previously described ( Luddi et al, 2022 ). Once resuspended, the samples were smeared into glass slides and left to dry.…”

Section: Methodsmentioning

confidence: 99%

Case report: The CCDC103 variant causes ultrastructural sperm axonemal defects and total sperm immotility in a professional athlete without primary ciliary diskinesia

et al. 2023

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Primary ciliary dyskinesia (PCD) is an inherited autosomal-recessive disorder characterized by abnormal ciliary motion, due to a defect in ciliary structure and/or function. This genetic condition leads to recurrent upper and lower respiratory infections, bronchiectasis, laterality defect, and subfertility. Male infertility is often associated with PCD, since the ultrastructure of the axoneme in the sperm tail is similar to that of the motile cilia of respiratory cells. We present the first reported case of a male patient from a non-consanguineous Italian family who exhibited a severe form of asthenozoospermia factor infertility but no situs inversus and absolutely no signs of the clinical respiratory phenotype, the proband being a professional basketball player. Whole-exome sequencing (WES) has identified a homozygote mutation (CCDC103 c.461 A>C, p.His154Pro) in the proband, while his brother was a heterozygous carrier for this mutation. Morphological and ultrastructural analyses of the axoneme in the sperm flagellum demonstrated the complete loss of both the inner and outer dynein arms (IDA and ODA, respectively). Moreover, immunofluorescence of DNAH1, which is used to check the assembly of IDA, and DNAH5, which labels ODA, demonstrated that these complexes are absent along the full length of the flagella in the spermatozoa from the proband, which was consistent with the IDA and ODA defects observed. Noteworthy, TEM analysis of the axoneme from respiratory cilia showed that dynein arms, although either IDAs and/or ODAs seldom missing on some doublets, are still partly present in each observed section. This case reports the total sperm immotility associated with the CCDC103 p.His154Pro mutation in a man with a normal respiratory phenotype and enriches the variant spectrum of ccdc103 variants and the associated clinical phenotypes in PCD, thus improving counseling of patients about their fertility and possible targeted treatments.

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“… 27 In a recently published paper, the authors confirm that only Leydig cells and not Sertoli cells are infected, which is further validated by postmortem specimens showing significant seminiferous tubular damage and decreased levels of Leydig cells. 28 Inflammation, COVID-19, and stress affect the integrity of the hypothalamic-pituitary axis. The reduced testosterone production will impair spermatogenesis, and the beneficial immunomodulatory and anti-inflammatory actions will be lost.…”

Section: Causes For Deterioration Of Sfa Parameters In Covid-19 Casesmentioning

confidence: 99%

“…Luddi et al show that viral replication in male gametes happens in more than one step and that viral particles can be separated at the middle of the sperm tail. 28 …”

Section: Does Seminal Fluid Carry the Covid-19 Virus?mentioning

confidence: 99%

Seminal fluid changes in the COVID-19 era: During infection and Post-vaccination

Nori¹,

Salman²

2023

gocm

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Coronavirus disease 2019 (COVID-19) predilection for angiotensin-converting enzyme 2 (ACE2) receptors allows its entrance and replication; however, they are not biochemically required for viral fusion into the cell membrane. Testicular tissue has abundant ACE2 receptors, making it a target for the COVID-19 virus. Seminal fluid parameters are measures of male fertility. Changes in semen parameters have been caused by coronavirus disease and vaccines. Some attribute that effect to direct hematogenic spread to the testis; others propose that the excessive immunological response triggered by the infection causes a deleterious effect. An unsubstantiated claim questioned whether the SARS-CoV-2 vaccine could trigger an unintentional immunological response that would impair male fertility once receiving the vaccine. Extensive research confirms the transient nature of those changes that affect sperm motility and count with full recovery post-COVID-19 infection and after vaccination. The vaccine's safety was reaffirmed; however, there are currently no recommendations for screening sperm donors. Research is warranted to guarantee the safety of couples undergoing assisted reproduction.

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Cellular and Molecular Mechanisms of In Vivo and In Vitro SARS-CoV-2 Infection: A Lesson from Human Sperm

Cited by 7 publications

References 39 publications

SARS-CoV-2 infection reduces quality of sperm parameters: prospective one year follow-up study in 93 patients

SARS-CoV-2 infection reduces quality of sperm parameters: prospective one year follow-up study in 93 patients

Case report: The CCDC103 variant causes ultrastructural sperm axonemal defects and total sperm immotility in a professional athlete without primary ciliary diskinesia

Seminal fluid changes in the COVID-19 era: During infection and Post-vaccination

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