Preliminary evidence of a paternal-maternal genetic conflict on the placenta: Link between imprinting disorder and multi-generational hypertensive disorders

Naruse, Katsuhiko; Tsunemi, Taihei; Kawahara, Naoki; Kobayashi, Hiroshi

doi:10.1016/j.placenta.2019.02.009

Cited by 8 publications

(6 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A sensitivity analysis indicated no significant effects using cut points at 36 or 38 weeks for preterm birth. Verification of this result is needed, which could be mediated by paternal influences on placental function, 37 but may be a chance finding. However, there were more frequent adverse events in men randomized to folic acid and zinc supplementation compared with placebo, indicating these doses of folic acid and zinc may be poorly tolerated by some men.…”

Section: Discussionmentioning

confidence: 99%

Effect of Folic Acid and Zinc Supplementation in Men on Semen Quality and Live Birth Among Couples Undergoing Infertility Treatment

Schisterman

Sjaarda

Clemons

et al. 2020

JAMA

114

View full text Add to dashboard Cite

IMPORTANCE Dietary supplements marketed for male fertility commonly contain folic acid and zinc based on limited prior evidence for improving semen quality. However, no large-scale trial has examined the efficacy of this therapy for improving semen quality or live birth.OBJECTIVE To determine the effect of daily folic acid and zinc supplementation on semen quality and live birth. DESIGN, SETTING, AND PARTICIPANTSThe Folic Acid and Zinc Supplementation Trial was a multicenter randomized clinical trial. Couples (n = 2370; men aged Ն18 years and women aged 18-45 years) planning infertility treatment were enrolled at 4 US reproductive endocrinology and infertility care study centers between June 2013 and December 2017. The last 6-month study visit for semen collection occurred during August 2018, with chart abstraction of live birth and pregnancy information completed during April 2019.INTERVENTIONS Men were block randomized by study center and planned infertility treatment (in vitro fertilization, other treatment at a study site, and other treatment at an outside clinic) to receive either 5 mg of folic acid and 30 mg of elemental zinc (n = 1185) or placebo (n = 1185) daily for 6 months. MAIN OUTCOMES AND MEASURESThe co-primary outcomes were live birth (resulting from pregnancies occurring within 9 months of randomization) and semen quality parameters (sperm concentration, motility, morphology, volume, DNA fragmentation, and total motile sperm count) at 6 months after randomization. RESULTS Among 2370 men who were randomized (mean age, 33 years), 1773 (75%) attended the final 6-month study visit. Live birth outcomes were available for all couples, and 1629 men (69%) had semen available for analysis at 6 months after randomization. Live birth was not significantly different between treatment groups (404 [34%] in the folic acid and zinc group and 416 [35%] in the placebo group; risk difference, −0.9% [95% CI, −4.7% to 2.8%]). Most of the semen quality parameters (sperm concentration, motility, morphology, volume, and total motile sperm count) were not significantly different between treatment groups at 6 months after randomization. A statistically significant increase in DNA fragmentation was observed with folic acid and zinc supplementation (mean of 29.7% for percentage of DNA fragmentation in the folic acid and zinc group and 27.2% in the placebo group; mean difference, 2.4% [95% CI, 0.5% to 4.4%]). Gastrointestinal symptoms were more common with folic acid and zinc supplementation compared with placebo (abdominal discomfort or pain: 66 [6%] vs 40 [3%], respectively; nausea: 50 [4%] vs 24 [2%]; and vomiting: 32 [3%] vs 17 [1%]).CONCLUSIONS AND RELEVANCE Among a general population of couples seeking infertility treatment, the use of folic acid and zinc supplementation by male partners, compared with placebo, did not significantly improve semen quality or couples' live birth rates. These findings do not support the use of folic acid and zinc supplementation by male partners in the treatment of infertility.

show abstract

Section: Discussionmentioning

confidence: 99%

Effect of Folic Acid and Zinc Supplementation in Men on Semen Quality and Live Birth Among Couples Undergoing Infertility Treatment

Schisterman

Sjaarda

Clemons

et al. 2020

JAMA

114

View full text Add to dashboard Cite

show abstract

“…This raises the possibility that the paternal sperm epigenome may influence maternal health during pregnancy in addition to that of the developing fetus. Hypertensive disorders in pregnancy have been associated with increased risk for developing cardiovascular disease (Naruse et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, it is an emerging concept that the paternal environment including factors such as diet and age can influence placental development and function. It is known that paternally expressed genes contribute to placental growth, trophoblast invasion and insulin resistance and adiposity (Moore, 2001;Binder, Hannan and Gardner, 2012;Wang et al, 2013;Rosenfeld, 2015;Naruse et al, 2019;. In humans, errors in epigenomic programming have been associated with gestational trophoblast disease and pre-eclampsia, but the role of the obese father in these conditions has been entirely unexplored (Gabory, Attig and Junien, 2011;Nelissen et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Remarkably, deregulated expression of genes implicated in inflammation has been implicated in hypertensive disorders in pregnancy including pre-eclampsia. Hypertensive disorders in pregnancy have been associated with increased risk for developing cardiovascular disease [117]. This raises the possibility that the paternal sperm epigenome may influence maternal health during pregnancy in addition to that of the developing fetus.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Sperm Histone H3 Lysine 4 tri-methylation serves as a metabolic sensor of paternal obesity and is associated with the inheritance of metabolic dysfunction

Pépin

Lafleur

Lambrot

et al. 2021

Preprint

View full text Add to dashboard Cite

Parental environmental exposures can strongly influence descendant risks for adult disease. Metabolic disorders arise from the intersection of environmental and genetic risk factors, with epigenetic inheritance being at the center of the familial cycle of transgenerational disease. How paternal high-fat diet changes the sperm chromatin leading to the acquisition of metabolic disease in offspring remains controversial and ill-defined. Using a genetic model of epigenetic inheritance, we investigated the role of histone H3 lysine 4 methylation (H3K4me3) in the paternal transmission of metabolic dysfunction. We show that obesity-induced alterations in sperm H3K4me3 associated with offspring phenotypes and corresponded to embryonic and placental chromatin profiles and gene expression. Transgenerational susceptibility to metabolic disease was only observed when grandsires had a pre-existing genetic predisposition to metabolic dysfunction that was associated with enhanced alterations to sperm H3K4me3. This non-DNA based knowledge of inheritance has the potential to improve our understanding of how environment shapes heritability and may lead to novel routes for the prevention of disease.

show abstract

“…Although experts have yet to scope a consensus on preeclampsia etiology, they do agree that vascular remodeling is abnormal. 4,5 Dysfunctional trophoblast contributes to deficient placentation which, in turn, prompts development of preeclampsia, particularly early-onset preeclampsia. 6,7 Therefore, placenta examination is crucial in the search for the spectrum of maternal vascular malperfusion.…”

Section: Introductionmentioning

confidence: 99%

More Tools for Evaluating Decidual Artery Disease

Contreras

Zuluaga

2022

Int J Surg Pathol

View full text Add to dashboard Cite

Introduction: Hypertensive disorders of pregnancy continue to pose the most important risks for adverse maternal and neonatal outcome. Among histological findings, decidual artery disease is one of the most common, one that has both good reproducibility among observers and whose abnormal vascular remodeling is the sole aspect of preeclampsia pathophysiology on which experts agree. Nevertheless, some aspects of arterial remodeling alterations are still under investigation. Methods: We selected 720 routine and consecutive placenta case studies, concordant with the Amsterdam consensus. From these studies, we collected maternal and neonatal clinical data and specific placental findings on spiral artery abnormalities. We took into account all criteria for decidual arteriopathy. Two hundred and fifteen (215) cases out of this population presented hypertensive disorders of pregnancy. Additional to expected arterial findings, we noted frequent persistent parietal trophoblast lining. Results: A large proportion of our population developed hypertensive disorders of pregnancy (30%). Among the histologic findings reported for preeclampsia, we paid particular attention to spiral artery abnormalities, and this interpretive analysis revealed high frequency of arterial remodeling abnormalities. We examined two additional aspects in our routine analysis: first, the novel one of parietal trophoblast persistence, and second, the established problem of associated acute inflammation, as a possible pitfall. Conclusion: In order to better understood, spiral maternal artery remodeling merits further study. The abnormalities in this process provide an objective tool in the study and diagnosis of important pregnancy complications; furthermore, abnormal remodeling is an expression of early pregnancy alteration, and subsequently related to preeclampsia etiology.

show abstract

Preliminary evidence of a paternal-maternal genetic conflict on the placenta: Link between imprinting disorder and multi-generational hypertensive disorders

Cited by 8 publications

References 39 publications

Effect of Folic Acid and Zinc Supplementation in Men on Semen Quality and Live Birth Among Couples Undergoing Infertility Treatment

Effect of Folic Acid and Zinc Supplementation in Men on Semen Quality and Live Birth Among Couples Undergoing Infertility Treatment

Sperm Histone H3 Lysine 4 tri-methylation serves as a metabolic sensor of paternal obesity and is associated with the inheritance of metabolic dysfunction

More Tools for Evaluating Decidual Artery Disease

Contact Info

Product

Resources

About