Unexplained recurrent miscarriages are associated with an aberrant sperm protamine mRNA content

Rogenhofer, Nina; Ott, Johannes; Pilatz, Adrian; Wolf, Julia; Thaler, Christian J.; Windischbauer, Lisa; Schagdarsurengin, Undraga; Steger, Klaus; Schönfeldt, Viktoria von

doi:10.1093/humrep/dex224

Cited by 28 publications

(15 citation statements)

References 28 publications

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“…In line with our findings, Rogenhofer et al [45] recently conducted an observational study and reported significant differences in PMN1 and PMN2 mRNA levels and the ratio of PMN1 to PMN2 mRNA between couples with recurrent miscarriages and healthy controls (p< 0.01). Despite the small sample size and ambiguity regarding the precise mechanism, they suggested that the levels of protamine gene expression in spermatozoa were not only essential for successful fertilization, but also for appropriate early embryo development [45]. In contrast, Torregrosa et al [46] reported no relationship between PMN2 gene expression and sperm DNA integrity.…”

Section: Discussionsupporting

confidence: 92%

The effect of vitamin C on the gene expression profile of sperm protamines in the male partners of couples with recurrent pregnancy loss: A randomized clinical trial

Hamidian

Talebi

Fesahat

et al. 2020

Clin Exp Reprod Med

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Objective: Since sperm abnormalities are known to be a major reason for recurrent pregnancy loss (RPL), any defects in DNA structure and chromatin condensation can place embryos at risk in the early stage of development and implantation. As antioxidants such as vitamin C may play a protective role against the destruction of protamine genes in sperm chromatin, this study was conducted to evaluate the effects of vitamin C on chromatin and the expression of protamine genes in the male partners of couples with RPL. Methods: Twenty male partners of couples with RPL were selected as the intervention group and received vitamin C supplementation (250 mg daily for 3 months). Healthy fertile men (n = 20) were included as controls. Sperm chromatin, DNA integrity, and the expression levels of protamine genes were evaluated before and after treatment. Results: Significant differences were found in sperm morphology, protamine deficiency, and apoptosis between the two groups and before and after vitamin C administration. A significant change was found in mRNA levels of PRM1, PRM2, and the PRM1/PRM2 ratio after treatment. Conclusion: Daily oral administration of vitamin C may improve human sperm parameters and DNA integrity by increasing protamine gene expression levels in the male partners of couples with RPL. The beneficial effects of vitamin C supplementation as an antioxidant for the male partners of couples with RPL could lead to improved pregnancy outcomes in these cases. This is an Open Access article distributed under the terms of the Creative Commons AttributionNon-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. www.eCERM.org S Hamidian et al. The effect of vitamin C on sperm gene expression

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Section: Discussionsupporting

confidence: 92%

The effect of vitamin C on the gene expression profile of sperm protamines in the male partners of couples with recurrent pregnancy loss: A randomized clinical trial

Hamidian

Talebi

Fesahat

et al. 2020

Clin Exp Reprod Med

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“…Similarly, ICSI with testicular sperm from Tnp1 −/− Tnp2 +/− males yielded higher implantation rates and more offspring than obtained by ICSI of Tnp1 −/− Tnp2 +/− cauda epididymal sperm [88]. In men, impaired sperm protamination is associated with recurrent miscarriages [89] and decreased fertilization rates in ART programs [23][24][25]. Thus, in light of the molecular mechanism provided in this study, ICSI with testicular sperm presents as only treatment option for subfertile men with impaired protamination and severe DNA fragmentation.…”

Section: Discussionmentioning

confidence: 93%

Protamine-2 Deficiency Initiates a Reactive Oxygen Species (ROS)-Mediated Destruction Cascade during Epididymal Sperm Maturation in Mice

Schneider

Shakeri

Trötschel

et al. 2020

Cells

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Protamines are the safeguards of the paternal sperm genome. They replace most of the histones during spermiogenesis, resulting in DNA hypercondensation, thereby protecting its genome from environmental noxa. Impaired protamination has been linked to male infertility in mice and humans in many studies. Apart from impaired DNA integrity, protamine-deficient human and murine sperm show multiple secondary effects, including decreased motility and aberrant head morphology. In this study, we use a Protamine-2 (Prm2)-deficient mouse model in combination with label-free quantitative proteomics to decipher the underlying molecular processes of these effects. We show that loss of the sperm’s antioxidant capacity, indicated by downregulation of key proteins like Superoxide dismutase type 1 (SOD1) and Peroxiredoxin 5 (PRDX5), ultimately initiates an oxidative stress-mediated destruction cascade during epididymal sperm maturation. This is confirmed by an increased level of 8-OHdG in epididymal sperm, a biomarker for oxidative stress-mediated DNA damage. Prm2-deficient testicular sperm are not affected and initiate the proper development of blastocyst stage preimplantation embryos in vitro upon intracytoplasmic sperm injection (ICSI) into oocytes. Our results provide new insight into the role of Prm2 and its downstream molecular effects on sperm function and present an important contribution to the investigation of new treatment regimens for infertile men with impaired protamination.

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“…54 Furthermore, a recent study by Rogenhofer et al demonstrated that P1 and P2 mRNA levels as well as the ratio of these two protamines were significantly different in male partners of women with unexplained recurrent pregnancy loss compared with healthy control men and subfertile couples undergoing in vitro fertilization/intracytoplasmic sperm injection. 55 Based on the current body of evidence, we believe we can hypothesize that sperm epigenetics impact embryo development and alterations can be implicated in pregnancy loss. We await further studies on this idea.…”

Section: Miscarriagesmentioning

confidence: 99%

Sperm Epigenetics and Its Impact on Male Fertility, Pregnancy Loss, and Somatic Health of Future Offsprings

Ibrahaim

Hotaling

2018

Semin Reprod Med

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Sperm epigenetic programming is tailored to meet the need of this specialized cell, which include its interaction with the oocyte during fertilization and early embryo development. The unique nature of the sperm epigenome has resulted in multiple studies investigating how perturbations in epigenetics might impact male fertility and early embryo development. In addition, sperm epigenetics appear to be altered by specific environmental exposures, which could provide a link for investigating the role of these triggers in somatic health of off springs produced. This has the potential of explaining otherwise missing heritability factors seen with several diseases. While this field of investigation is new and with limited validation, it is intriguing and further studies are warranted.

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Unexplained recurrent miscarriages are associated with an aberrant sperm protamine mRNA content

Abstract: N/A.

Cited by 28 publications

References 28 publications

The effect of vitamin C on the gene expression profile of sperm protamines in the male partners of couples with recurrent pregnancy loss: A randomized clinical trial

The effect of vitamin C on the gene expression profile of sperm protamines in the male partners of couples with recurrent pregnancy loss: A randomized clinical trial

Protamine-2 Deficiency Initiates a Reactive Oxygen Species (ROS)-Mediated Destruction Cascade during Epididymal Sperm Maturation in Mice

Sperm Epigenetics and Its Impact on Male Fertility, Pregnancy Loss, and Somatic Health of Future Offsprings

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