Fertility is a complex pathophysiological condition that can be caused by multiple physical and physiological factors, including hormonal imbalances, genetic alterations, and abnormalities in homeostasis. Recent studies also indicate that epigenetic mechanisms may be associated with reproductive fertility, including transgenerational effects.

Epigenetics are heritable modifications to DNA bases and chromatin proteins that do not alter the base pair sequence but can enhance or repress its transcription. Epigenetics is essential to normal biological processes and functioning, but it can also play an important role in disease and fertility.

Epigenetic Factors Impacting Female Reproduction

Related to fertility, epigenetic factors – particularly for women in later reproductive years – can include alterations in DNA methyltransferase (DNMT) levels, DNA methylation levels, and histone acetylation and methylation patterns. With aging, DNMT regulation is altered, generally, to include altered levels of transcription of genes involved in establishing and maintaining DNA methylation. There is also a negative relationship between DNA methylation and fragmentation of DNA. Individuals who smoke may also be at a higher risk for impacts on DNA methylation during the development of fetuses during pregnancy.

Ultimately, these processes can demonstrate epigenetic instability during gametogenesis and embryogenesis that alters gene expression patterns. Consequences of altered DNA methylation can include the decreased expression of many important genes, including those that are essential for cell cycle control and meiotic chromosomal segregation.

In addition to advanced maternal age, the presence of Type 1 or Type 2 diabetes may impact epigenetic fetal evolution. Obesity and lack of mobility in the mother have been identified as having epigenetic causes for pregnancy Type 2 diabetes, which can alter the embryonic environment and gene programming, increasing the risk of congenital anomalies, such a s premature birth, microencephaly, intellectual impairment, genitourinary anomalies, hypoplasia, fetal heart disease, limb defects, stillbirths, and postpartum deaths.

Epigenetic Factors Impacting Male Reproduction

Some cases of male infertility can be attributed to epigenetic events of spermatogenesis, such as chromosome condensation, genomic packaging in the spermatid nucleus, and the presence of retrotransposons. While recent research indicates a strong role of environmental factors, epigenetics play a strong role in governing abnormal spermatozoa maturation and function.

In addition to spermatogenesis failure, epigenetics can also impact male reproduction during embryo development, genomic imprinting during assisted reproduction, and even influence long-term effects on the offspring throughout its lifetime.

Environmental Factors Influencing Epigenetics & Reproduction

One of the most intriguing aspects of many recent epidemiological studies is the evidence that the lifestyle of one generation can modify the risk of developing chronic disease or infertility in subsequent generations. Lifestyle factors that can impact the health and development of descendants may include elements such as:

  • Diet & Physical Activity Levels: Nutritional status and physical activity levels are often associated with dynamic epigenetic changes in spermatozoa, indicating that pre-conception lifestyle factors can modulate the health of the offspring through gamete epigenetic inheritance.
  • Smoking, Alcohol Consumption & Sedentarism: Unhealthy lifestyle factors, such as smoking, alcohol consumption, and sedentarism, can result in a variety of neuroendocrine, immune, and behavioral responses that impact the reproductive potential of adults.
  • Environmental Stress: Environmental stress can cause different patterns of gene expression in different cells and influence the health and development of offspring.

These modifiable lifestyle factors play a crucial role in not only current reproductive functioning in both parents but may have long-lasting implications for future generations. While additional research is necessary to fully understand these effects, current data already indicates that lifestyle factors are strongly associated with dynamic epigenetic changes to fertility and throughout the reproductive process.


Epigenetics, particularly when analyzed in light of environmental, maternal, and paternal factors, have a strong role in fertility and infertility. Critical changes that can impact infertility can be identified by examining the entire genome and epigenome and determining the mechanisms of environmental effects in the manipulation of epigenetic variables.

A greater understanding of the nature of the gametic epigenome pattern can create new insights for future directions of infertility treatments through the modification of the epigenome code in specific genetic elements without changing the heritage of the nucleotides. The ultimate goal of this direction of study can be to introduce active or inactive genes that are responsible for normal developmental adjustments and targeted environmental changes of genes to benefit the individual, their reproductive health including the management and treatment of reproductive disorders, and the long-term health of their offspring.