A systematic review on the role of paternal factors in human placental development, function, and pregnancy-related disorders

Jeslin Johnson; Sweta Nair; Dipty Singh; Nafisa H. Balasinor; Kumari Nishi

doi:10.1007/s10815-025-03594-3

Genetics and Immunology Reproductive Genetics

A systematic review on the role of paternal factors in human placental development, function, and pregnancy-related disorders

Johnson J, Nair S, Singh D, Balasinor NH, Nishi K

Published October 2025 Journal of Assisted Reproduction and Genetics, 42(10), 3183-3216

DOI 10.1007/s10815-025-03594-3 PMC PMC12602764

RRM Academy Synopsis

Father's age and smoking are associated with pregnancy complications

A systematic review of 48 studies found that a father's age, smoking and chemical exposure were linked to placental problems and pregnancy complications. Most were cohort or case–control studies. Three studies linked sperm DNA fragmentation to repeated miscarriage.

Key Findings

The review covered 48 studies: 21 cohort studies, 25 case–control studies and 2 randomized controlled trials. Eleven studies examined paternal age.
Older fathers were reported to carry higher risks of preeclampsia, spontaneous abortion, preterm birth and stillbirth, and heavier placentas and babies.
Five studies examined paternal smoking, reported as a risk factor for placental abruption and stillbirth. One study calculated abruption risk as five-fold for both parents smoking and two-fold individually.
Higher phthalate metabolite levels in fathers' urine went with lower birth weight in singletons born through in vitro fertilization, and DEHP metabolites with reduced placental weight.
Three studies reported increased sperm DNA fragmentation to be associated with recurrent spontaneous abortion. Three reported increased seminal oxidative stress to be associated with it.

Interpretation

Apart from two randomized trials on semen and sperm factors, the studies are observational, so the findings describe associations. The authors note that the paternal genome contributes to placental growth and development. They report that paternal factors may alter the seminal plasma proteome, the cytokine profile and the DNA methylation of imprinted genes in sperm, which they link with adverse pregnancy outcomes. The authors also note that few studies exist on fathers and the placenta.

RRM Context

Restorative reproductive medicine evaluates both partners. The review adds a father's age, smoking, chemical exposure and sperm quality to the factors linked with pregnancy outcomes. The authors suggest that checking fathers' health before conception might help the placenta develop well.

Our editorial summary of this paper, not the article's abstract.

Abstract

Background

The human placenta plays an important role in pregnancy and offspring health. The paternal genome contributes significantly to placental growth and development. While the maternal factors affecting gestational health are thoroughly investigated, the paternal factors are often overlooked. Thus, it is important to understand various paternal factors affecting placental development and function.

Objective

To assess the effect of various paternal factors on placental development, function, and pregnancy-related disorders.

Materials and Methods

This review was registered in PROSPERO (Registration number CRD420250634649). Literatures across databases like JSTOR, Scopus, Google Scholar, ScienceDirect, and PubMed were screened through a set of criteria. Forty-eight studies were selected that included low-to-moderate risk paternal factors like age, smoking, race/ethnicity/location, genetic, epigenetic factors, exposure to chemicals, seminal plasma, and lifestyle factors.

Results

Increased paternal age was reported to contribute towards higher risks of preeclampsia, spontaneous abortions, preterm birth, stillbirth, and higher placental and fetal birth weight. Paternal smoking, on the other hand, was found to be an associated risk factor for placental abruption and stillbirth. Exposure to various chemicals was found to be associated with changes in sperm epigenome and placental dysfunction.

Discussion and Conclusions

Paternal health, lifestyle, and exposure to chemicals may affect placental development and pregnancy. Paternal factors may alter seminal plasma proteome, cytokine profile, and abnormal sperm DNA methylation of imprinted genes which is associated with adverse pregnancy outcomes. Pre-conceptional health assessment of prospective fathers might be helpful in ensuring optimal placental development in pregnancies to follow, in addition to newborn health.

Topics

Genetics and Immunology › Reproductive Genetics › Epigenetics · Lifestyle and Environment › Environmental Exposures › Endocrine Disrupting Chemicals · Pregnancy › Pregnancy Complications › Hypertensive Disorders

Jeslin Johnson, Sweta Nair, Dipty Singh, Nafisa H. Balasinor, Kumari Nishi

J Johnson, S Nair, D Singh, N Balasinor, K Nishi

DOI 10.1007/s10815-025-03594-3 10.1007/s10815-025-03594-3 Johnson et al. 2025, Johnson 2025

A systematic review on the role of paternal factors in human placental development, function, and pregnancy-related disorders

Father's age and smoking are associated with pregnancy complications

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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