Preeclampsia: What Does the Father Have to Do with It?

Katsi, Vasiliki; Felekos, Ioannis; Siristatidis, Charalampos; Kasioni, Spyridoula; Drakontaidis, A.; Farmakides, George; Makris, Thomas; Aggeli, Constadina; Nihoyannopoulos, Petros; Tousoulis, Dimitrios; Kallikazaros, Ioannis

doi:10.1007/s11906-015-0576-7

Cited by 11 publications

(11 citation statements)

References 30 publications

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“…Importantly, this association may be determined by the genotype of the child, not the genotype of the mother. These observations are consistent with the known paternal influence on preeclampsia, 57 since APOL1 allele contributions from each parent appear necessary to predispose the mother to an at-risk pregnancy.…”

Section: Discussionsupporting

confidence: 86%

APOL1-G0 or APOL1-G2 Transgenic Models Develop Preeclampsia but Not Kidney Disease

Bruggeman

Luo

et al. 2016

JASN

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APOL1 risk variants are associated with kidney disease in blacks, but the mechanisms of renal injury associated with APOL1 risk variants are unknown. Because APOL1 is unique to humans and some primates, we created transgenic (Tg) mice using the promoter of nephrin-encoding Nphs1 to express the APOL1 reference sequence (G0) or the G2 risk variant in podocytes, establishing Tg lines with a spectrum of APOL1 expression levels. Podocytes from Tg-G0 and Tg-G2 mice did not undergo necrosis, apoptosis, or autophagic cell death in vivo, even in lines with highly expressed transgenes. Further, Tg-G0 and Tg-G2 mice did not develop kidney pathology, proteinuria, or azotemia as of 300 days of age. However, by 200 days of age, Tg-G2 mice had significantly lower podocyte density than age-matched WT and Tg-G0 mice had, a difference that was not evident at weaning. Notably, a pregnancy-associated phenotype that encompassed eclampsia, preeclampsia, fetal/neonatal deaths, and small litter sizes occurred in some Tg-G0 mice and more severely in Tg-G2 mice. Similar to human placenta, placentas of Tg mice expressed APOL1. Overall, these results suggest podocyte depletion could predispose individuals with APOL1 risk genotypes to kidney disease in response to a second stressor, and add to other published evidence associating APOL1 expression with preeclampsia.

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Section: Discussionsupporting

confidence: 86%

APOL1-G0 or APOL1-G2 Transgenic Models Develop Preeclampsia but Not Kidney Disease

Bruggeman

Luo

et al. 2016

JASN

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“…The less favorable outcome for female only carriers or homozygotes versus males also suggests that the maternal contribution is not confined to the transmission of the M2 haplotype to the fetus and needs further elucidation. There is growing evidence that male factors are important for abnormal placentation and the development of PE (Κatsi et al, 2015). The association shown in this study of the paternal ANXA5 M2 haplotype with adverse outcomes adds weight to the hypothesis that male factors play also play a role in PMPC.…”

Section: Discussionmentioning

confidence: 99%

Precision Medicine in Assisted Conception: A Multicenter Observational Treatment Cohort Study of the Annexin A5 M2 Haplotype as a Biomarker for Antithrombotic Treatment to Improve Pregnancy Outcome

Fishel¹,

Baker²,

Elson³

et al. 2016

eBioMedicine

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BackgroundPregnancy failure and placenta mediated pregnancy complications affect > 25% of pregnancies. Although there is biological plausibility for a procoagulant mechanism underlying some of these events, antithrombotic intervention trials demonstrate limited benefit, possibly through lack of stratification in heterogeneous patient groups. The ANXA5 M2 haplotype is a possible procoagulant biomarker and was tested pragmatically to determine whether this screening and LMWH treatment normalized the outcome for ANXA5 M2 positive couples.This was a pragmatic study that aimed to measure the effectiveness of a testing (for the M2 haplotype) and treatment (LMWH) pathway in routine clinical practice where there is variation between patients. Such a study in couples with fertility problems can inform choices between treatments; it is then the management protocol which is the subject of the investigation, not the individual treatments.MethodsCouples (N = 77) with one or both partners ANXA5 M2 positive demonstrated association of this haplotype with adverse IVF outcome. A pragmatic, multicenter, prospective cohort study of ANXA5 M2 haplotype screening, and LWMH treatment following embryo transfer (ET) in 103 IVF couples positive for ANXA5 M2 was performed. They were compared with a group of 1000 contemporaneous randomly selected unscreened and untreated couples undergoing assisted conception, from which 103 matched control couples were derived. The primary outcome measure was live birth incidence. Secondary outcomes were results following embryo transfer (ET) and live birth outcome by gender and M2 carriage, and allelic dose influence.FindingsThe tested and treated cohort of ANXA5 M2 carriers achieved a similar live birth rate (37.9%) per ET cycle compared to both the more fertile comparison group (38.5%), and to the 103 matched controls (33.0%). Significantly more treated male carrier only couples had a live birth versus female M2 only (47.7% vs. 25.0% p = 0.045).InterpretationPragmatic ANXA5 M5 screening and treatment with LMWH in couples undergoing IVF is associated with similar outcome to couples with more favorable prognostic factors. The difference in live birth outcome for treated male only carrier couples may be consistent with an additional maternal thrombophilic factor that may adversely affect pregnancy, although other mechanisms are possible. This study suggests that LMWH treatment should be started prior to clinical pregnancy.

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“…47 The only meta-analyses exploring paternal factors investigated the contribution of anti-paternal human leucocyte antibodies (HLA) and suggested that human leukocyte antigen G (HLA-G) expressed on the invading cytotrophoblast is important for the maternal adaptation of the placental vessels. 48 A shorter duration of exposure to seminal fluid is responsible for an increased risk of developing pre-eclampsia. 47 This is also demonstrated by an escalated risk of pre-eclampsia in pregnancies conceived as a result of ovum donation in azoospermic partners and after a short duration or a single act of unprotected intercourse.…”

Section: Paternal Mental Healthmentioning

confidence: 99%

“…54 Furthermore, studies on paternal family history of genetic thrombophilia, hypertension, and cardiovascular disease reflect genes passed through the feto-placental unit via the father, which are associated with a number of adverse pregnancy outcomes. 48 This may be through single-nucleotide polymorphisms in the paternally expressed insulin-like growth factor (IGF2), which is responsible for trophoblastic invasion and placental function. 48 Likewise, there are several other possible pathways by which certain viruses, such as cytomegalovirus (CMV) and herpes virus, bacterial, fungal, and parasitic infections, have the potential to contribute to adverse pregnancy outcomes and, more specifically, to pre-eclampsia.…”

Section: Paternal Mental Healthmentioning

confidence: 99%

The forgotten father in obstetric medicine

et al. 2019

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The role of fathers prior to conception, during pregnancy, and in the post-partum period has generally not been a key consideration for Obstetric Physicians. However, this view may need challenging. This paper outlines the key importance of fathers in all phases of obstetric medical care. We review the contribution of paternal factors such as genetics, health, and lifestyle to fetal development, pregnancy complications, and maternal and neonatal wellbeing. The role of fathers in complex care decisions during pregnancy is also reviewed. Postpartum, fathers have a substantial role in shaping the future of the family unit through encouraging breastfeeding and creating a supportive environment for motherhood. This review proposes areas for future research and recommends an evidence-based change in practice in obstetric medicine that focuses on recognizing the role of fathers in the pregnancy journey.

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Preeclampsia: What Does the Father Have to Do with It?

Cited by 11 publications

References 30 publications

APOL1-G0 or APOL1-G2 Transgenic Models Develop Preeclampsia but Not Kidney Disease

APOL1-G0 or APOL1-G2 Transgenic Models Develop Preeclampsia but Not Kidney Disease

Precision Medicine in Assisted Conception: A Multicenter Observational Treatment Cohort Study of the Annexin A5 M2 Haplotype as a Biomarker for Antithrombotic Treatment to Improve Pregnancy Outcome

The forgotten father in obstetric medicine

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