Is There a Paternal (Sperm) Contribution to Embryo Development?
Taylor P. Kohn
Baylor College of Medicine
Alexander W. Pastuszak, MD, PhD
Division of Male Reproductive Medicine and Surgery
Scott Department of Urology
Baylor College of Medicine
Human embryo development begins when the paternal sperm fuses with the maternal egg, forming a zygote. Both the sperm and the egg contribute DNA, or genetic material, to the newly formed zygote, and this genetic material is packaged as chromosomes. Humans have two copies of 22 unique chromosomes in each cell – one copy from the egg and one from the sperm, as well as a combination of X and Y chromosomes that determine sex – for a total of 46 chromosomes (Table 1). The chromosomal DNA is expressed only beginning on the third day of the embryo’s development.1 While it is well known that both the sperm and egg supply genetic material to the developing embryo, there are other contributions that the sperm makes to the embryo that are important for its development.. In addition to contributing half of the genetic material to the embryo, the sperm also contributes the centrosome, a subcellular organelle that helps the embryo grow..2 Another important sperm contribution to the zygote is the “oocyte activation factor,” which stimulates the zygote to complete its first cellular division and become an embryo. Finally, the sperm also contributes messenger RNA (mRNA - another form of genetic material), which contains instructions for protein production and can be used immediately to make proteins that are important for early development.. mRNA’s exact role in early embryo formation is not completely clear, but it appears to have an effect early in embryo development.1
Development of an embryo may be affected at any point. Abnormal sperm contributions resulting in either “early” or “late” sperm effects on embryo development have been identified. “Early” paternal effects are primarily defined by the absence of fertilization or poor zygote morphology (how the zygote looks under a microscope), and correlate with an absent or dysfunctional oocyte activation factor or a dysfunctional centrosome. These “early” sperm effects are evident during in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles when oocytes fail to fertilize or initially develop.1 In contrast, “late” paternal effects are manifested by poor embryo progression or development resulting in failure of the embryo to implant into the uterus. “Late” sperm effects correlate with abnormalities in sperm DNA, such as increased fragmentation (broken pieces) of sperm DNA, an indicator of low genetic quality, or an abnormal number of chromosomes coming from the male partner.1 While specific genes that may be affected by DNA breaks are unknown, studies examining fragmented or broken sperm DNA have shown that high levels of fragmentation are associated with decreased fertilization and pregnancy outcomes naturally or with intrauterine insemination (IUI), and assisted reproductive techniques such as IVF and ICSI.3 Additionally, the presence of too many or too few chromosomes in sperm cells, or additions or deletions in the sperm DNA, can hinder embryo development and induce embryo loss.1 Recent studies have also shown a higher rate of early embryo failure when levels of certain paternal mRNAs are decreased.4
While there is clearly a contribution of the sperm to fertilization and embryo development, the exact nature and extent of this contribution remains to be determined. In couples with recurrent miscarriage or IVF cycle failures, the reason for embryo loss is often debated and a cause is searched for. While the timing of the embryo loss may correlate with “early” or “late” effects that may be caused by sperm, it is often difficult to definitively attribute the cause of failure to either sperm or egg. The timing of embryo loss, however, can help guide clinicians in subsequent testing, particularly if a male factor has not been ruled out. In the future, definitive identification of sperm or egg factors resulting in fertility problems will become easier, paving the way for a more complete understanding of how the sperm contributes to this process.5
Table 1 – Paternal Sperm Contributions to Embryo Development
|Paternal Sperm Contributions
||(DNA) Genetic Material
||Maturation of the Oocyte
- Barroso G, Valdespin C, Vega E, et al: Developmental sperm contributions: fertilization and beyond. Fertility and Sterility 2009; 92: 835–848.
- Schatten G: The centrosome and its mode of inheritance: the reduction of the centrosome during gametogenesis and its restoration during fertilization. Dev. Biol. 1994; 165: 299–335.
- Kumar M, Kumar K, Jain S, et al: Novel insights into the genetic and epigenetic paternal contribution to the human embryo. Clinics (Sao Paulo) 2013; 68: 5–14.
- Simon A and Laufer N: Assessment and treatment of repeated implantation failure (RIF). J Assist Reprod Genet 2012; 29: 1227–1239.
- Bhattacharya SM: Association of various sperm parameters with unexplained repeated early pregnancy loss—which is most important? Int Urol Nephrol 2007; 40: 391–395.