Preimplantation development is a period of dynamic epigenetic change that begins with remodeling of egg and sperm genomes, and ends with implantation. During this time, parental-specific imprinting marks are maintained to direct appropriate imprinted gene expression. We previously demonstrated that H19 imprinting could be lost during preimplantation development under certain culture conditions. To define the lability of genomic imprints during this dynamic period and to determine whether loss of imprinting continues at later stages of development, imprinted gene expression and methylation were examined after in vitro preimplantation culture. Following culture in Whitten's medium, the normally silent paternal H19 allele was aberrantly expressed and undermethylated. However, only a subset of individual cultured blastocysts (approximately 65%) exhibited biallelic expression, while others maintained imprinted H19 expression. Loss of H19 imprinting persisted in mid-gestation conceptuses. Placental tissues displayed activation of the normally silent allele for H19, Ascl2, Snrpn, Peg3 and Xist while in the embryo proper imprinted expression for the most part was preserved. Loss of imprinted expression was associated with a decrease in methylation at the H19 and Snrpn imprinting control regions. These results indicate that tissues of trophectoderm origin are unable to restore genomic imprints and suggest that mechanisms that safeguard imprinting might be more robust in the embryo than in the placenta.
Johnson J et al., 2025·Journal of Assisted Reproduction and Genetics
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. To assess the effect of various paternal factors on placental development, function, and pregnancy-related disorders. 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. 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 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.
Male Endocrine and Genetic Factors · Genetic Causes of Male Infertility
Jenkins TG et al., 2016·Fertil Steril·
Open Access
To evaluate the relationship between epigenetic patterns in sperm and fecundity.
Prospective study.
Academic andrology and in vitro fertilization laboratory. PATIENT(S): Twenty-seven semen samples from couples who conceived within 2 months of attempting a pregnancy and 29 semen samples from couples unable to achieve a pregnancy within 12 months. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Genomewide assessment of differential sperm DNA methylation and standard semen analysis. RESULT(S): We analyzed DNA methylation alterations associated with fecundity in 124 semen samples, and identified regions of interest in 27 semen samples from couples who conceived within 2 months of attempting a pregnancy and a total of 29 semen samples from couples who were unable to achieve a pregnancy within 12 months. No differences in sperm count, sperm morphology, or semen volume were observed between the patients achieving a pregnancy within 2 months of study time and those not obtaining a pregnancy within 12 months. However, using data from the human methylation 450k array analysis we did identify two genomic regions with statistically significantly decreased (false discovery rate <0.01) methylation and three genomic regions with statistically significantly increased methylation in the failure-to-conceive group. The only two sites where decreased methylation was associated with reduced fecundity are at closely related genes known to be expressed in sperm, HSPA1L and HSPA1B. CONCLUSION(S): Our data suggest that there are genomic loci where DNA methylation alterations are associated with decreased fecundity. We have thus identified candidate loci for future study to verify these results and investigate the causative or contributory relationship between altered sperm methylation and decreased fecundity.
To describe two children diagnosed with Beckwith-Wiedemann Syndrome (BWS) arising from a spontaneous conception and an assisted reproductive technology (ART) cycle from one patient with a long-standing history of subfertility. Case report. Academic medical center.Patient(s)Two children with the morphologic features of BWS as a result of a spontaneous conception and an ART cycle from the same patient.Intervention(s)Assisted reproductive technology.Main outcome measure(s)Neonatal and pediatric morphologic evaluation by geneticists.Result(s)Two children with the morphologic features consistent with the criteria for the diagnosis of BWS.Conclusion(s)Patients with subfertility may be carriers for genetic disorders that can be passed to a child with or without the use of assisted reproductive technologies (ART). The use of ART may bypass natural selection mechanisms.