UNIT 1 - Epigenetics and Pregnancy |
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Epigenetics Transforming Health from Preconception to Early Childhood Ovulatory Infertility Declining Sperm and Semen Quality Article review Video review |
OBJECTIVES:
- Define epigenetics.
- Describe the lifestyle medicine approach to transform health from preconception to early childhood.
- Understand the role of epigenetics on pregnancy outcome.
- Discuss nutrition, ovulatory infertility, and sperm count and quality.
Epigenetics
The field of Epigenetics represents the science which helps us understand the influence life has on genetic function. Research has shown that what we do, what we are exposed to, and the internal and external environments have significant influence on the output of our genes. In this article, the reader will understand how alterations in the DNA explain how the genetic output us changed as a result of exposures to life. The field of epigenetics is a branch of science that helps us understand the impact life has on the function of genes. We have thought for some time that we were born with a genetic makeup that was fixed, but recent research has proven that what we do, what we are exposed to, and our internal and external environments have tremendous influence on the output of our DNA.
To a large degree the story of epigenetics is the story of nutritional deficiency and how these deficiencies affected the DNA, chromosomes, genes, proteins, and enzymes. All of this is the sum total of cellular chemistry. Now when we start to compare these nutritional deficiencies of the past, we can start to think about the pathophysiology of diabetes, obesity, cardiovascular disease, and even dementia and consider that these diseases might also be related to nutritional deficiencies. When we consider obesity, we know this is one of the common denominators for diabetes, metabolic syndrome, cardiovascular disease, and more, and in most cases individuals suffering from obesity eat an overabundance of calories but they are nonetheless malnourished. The latter is the result of eating foods high in calories but low in nutritional value. As a result, we know that it is important to provide a diet that is low in calories but high in nutritional value. The Mediterranean diet is a good example of such a diet, and research has shown that this type of eating affects the pregnancy rates in women. Karayiannis et al1 showed that women in the lowest tertile (those eating a diet not consistent with the Mediterranean diet) had significantly lower rates of pregnancy and live births. Those with higher MedScores had a 2.7 times higher likelihood of pregnancy and live birth. Toledo et al2 looked at 485 women age 20 to 45 years who reported difficulty getting pregnant and 1669 age-matched controls who had at least one child, and they found that the women in the highest quartile for use of the Mediterranean diet had significantly less difficulty getting pregnant.
To a large degree the story of epigenetics is the story of nutritional deficiency and how these deficiencies affected the DNA, chromosomes, genes, proteins, and enzymes. All of this is the sum total of cellular chemistry. Now when we start to compare these nutritional deficiencies of the past, we can start to think about the pathophysiology of diabetes, obesity, cardiovascular disease, and even dementia and consider that these diseases might also be related to nutritional deficiencies. When we consider obesity, we know this is one of the common denominators for diabetes, metabolic syndrome, cardiovascular disease, and more, and in most cases individuals suffering from obesity eat an overabundance of calories but they are nonetheless malnourished. The latter is the result of eating foods high in calories but low in nutritional value. As a result, we know that it is important to provide a diet that is low in calories but high in nutritional value. The Mediterranean diet is a good example of such a diet, and research has shown that this type of eating affects the pregnancy rates in women. Karayiannis et al1 showed that women in the lowest tertile (those eating a diet not consistent with the Mediterranean diet) had significantly lower rates of pregnancy and live births. Those with higher MedScores had a 2.7 times higher likelihood of pregnancy and live birth. Toledo et al2 looked at 485 women age 20 to 45 years who reported difficulty getting pregnant and 1669 age-matched controls who had at least one child, and they found that the women in the highest quartile for use of the Mediterranean diet had significantly less difficulty getting pregnant.
Chavarro et al looked at protein intake and infertility and found that the type of protein influenced pregnancy rates. For those eating more animal protein, the relative rate of infertility was 1.39 compared to 0.78 for those eating more vegetable protein. Goh et al4 looked at the use of multivitamin supplementation and found that micronutrients have a positive epigenetic effect resulting in 41% lower rates of infertility, fewer miscarriages, fewer birth defects, less pediatric cancer, and less autism. Cetin et al5 looked at the role of micronutrients in the periconception period. Compared to women who did not take multivitamins, those taking less than 2 tablets per week had a relative rate (RR) of infertility of 0.88. Those taking 3 to 5 tablets per week had a RR of 0.69, and those taking more than 6 tablets per week had a RR of only 0.59. This means the rate of pregnancy was better for those taking more vitamins— more evidence that nutrition make a significant difference.
Chavarro et al also reported that women who took iron supplements had a significantly lower risk of infertility. The adequate dose appeared to be 40 to 80 mg of iron daily. Studies in epigenetics also reveal that diet in the male partner also affects fertility. Attaman et al, in the journal Human Reproduction, looked at Danish males who ate mostly saturated fat and found 38% lower sperm concentration and 41% lower sperm counts. Similar studies in the United States found that walnuts improved but alcohol and cannabis impaired male fertility. Once we realize that external exposures affect genetic function, we start to question when preventive health care should start. The answer seems to be in the preconception period, but it is extremely concerning to know that the average in utero fetus has over 200 chemicals in the cord blood. This information makes the recommendation for preconception preventive health care even more important. Preconception recommendations should start 4 to 6 months prior to conception and should recommend stopping as many unhealthy foods as possible, avoiding as many environmental chemicals as possible, increasing the consumption of water and cruciferous vegetables, and considering detoxification. Health care providers should also discuss the impact of all the above with couples considering pregnancy. Pediatricians and gynecologists should talk with their patients about the use of vitamins, iron, and so on.
Transforming Health from Preconception to Early Childhood
Lifestyle medicine holds great promise to transform health during the period from preconception to early childhood. Genetic, epigenetic, nutritional, and environmental factors have lifetime impact on the newborn and family. Little is known about the full potential of lifestyle medicine to improve maternal, child, and family health. Additionally, health care providers face limits in time and may have gaps in knowledge, that preclude discussion of the impact lifestyle medicine can the mother, newborn, and family. Greater understanding of the potential impact of lifestyle medicine provides opportunities to identify current deficiencies in care and areas for improvement and highlights the need for further research. This article reviews current evidence supporting the 6 pillars of lifestyle medicine: nutrition, physical activity, sleep, avoiding risky substance use, stress management and social connectedness as applied to maternal child care from preconception to early childhood, examines the current state of practice, and identifies opportunities for both practice change and further research. Rather than view each component of care in isolation, viewing care as a continuum from preconception to childhood can best establish healthy habits and optimize outcomes for the entire family.
Despite the Healthy People 2000 objective for 60% of primary care physicians to provide age-appropriate preconception care, only 1 in 6 prenatal care physicians provided preconception care to the majority of their patients.3 Multidisciplinary teams, including lifestyle medicine practitioners, are ideally suited to optimize preconception health. Preconception care is “a set of interventions that aim to identify and modify biomedical, behavioral and social risks to the woman’s health or pregnancy outcome through prevention and management.” Effective preconception care affords the opportunity to provide health benefits of equal magnitude to comprehensive prenatal care. Improved access to and effective provision of preconception care is critical for improving perinatal outcomes.
In 2016, 77% of women who gave birth initiated prenatal care in the first trimester.4 Given the high rates of utilization, prenatal care may be the only opportunity to address the importance of lifestyle in pregnancy. Although the postpartum period offers numerous opportunities to positively affect health outcomes for the mother, her child, and family, and nearly half of maternal mortality occurs in the postpartum period, 40% of patients fail to complete even 1 postpartum visit. The care provided is often fragmented and does not result in a transition to comprehensive follow up. Increasing the frequency and quality of postpartum visits is a Healthy People 2020 goal. At the time of delivery, the medical team’s focus is early identification and prevention of complications. Recognizing that birth also has a powerful, positive impact on the future health of the infant is a step toward optimizing health and improving long-term outcomes. Bonding is key, and inpatient “rooming in” of mother and baby encourages collaboration by providers to create a positive start. Optimal care involves reviewing the 6 core pillars of lifestyle medicine and helping to meet these needs from the first moments of the child’s life. The message should be “Congratulations, you have given birth to a beautiful baby and we are going to do everything we can to ensure you, your child, and your family have a healthy, successful future.”
Ovulatory Infertility
According to the data from the National Survey of Family Growth (NSFG), infertility is defined as a lack of pregnancy in the 12 months prior to survey, despite having had unprotected sexual intercourse in each of those months with the same husband or partner. Impaired fecundity is defined as physical difficulty in either getting pregnant or carrying a pregnancy to live birth.7 The data from the NSFG reveal that the percentage of married, infertile women aged 15 to 44 fell from 8.5% in 1982 to 6.0% in 2010. Impaired fecundity among this same group increased from 11% in 1982 to 15% in 2002, but then fell again in 2010 to 12%. It is very difficult to assess the actual rates of infertility and subfecundity; however, there is an argument to be made that the rates of both are significantly higher even when considering ovulatory infertility only and dismissing male factor. Ovulatory infertility is directly related to polycystic ovarian syndrome (PCOS). PCOS gets its name from the appearance of the ovary on ultrasound, but metabolically what is happening is a constellation of obesity, insulin resistance, and oligo, or anovulation. As women become obese, they become insulin resistant. These elevated levels of circulating insulin suppress the synthesis of sex hormone binding globulin (SHBG), which is crucial in binding free androgens. So, when SHBG synthesis is suppressed, free androgens rise. Infrequent ovulation is the result of these elevated free androgens. A study done by Barnard and colleagues showed that SHBG is increased when women consume a low-fat plant-based diet. This increase happens because insulin resistance and free insulin are reduced and the synthesis of the SHBG is no longer suppressed.
Ovulatory infertility is affected by dietary intake. A study in the American Journal of Obstetrics and Gynecology showed that consuming 5% of total energy intake as animal protein, rather than in the form of carbohydrates, was associated with a 19% greater risk of ovulatory infertility. In contrast, consuming 5% of energy as vegetable protein, rather than as carbohydrates, was associated with a 43% lower risk of ovulatory infertility. Also, consuming 5% of energy as vegetable protein, as opposed to animal protein, was associated with a greater than 50% lower risk for ovulatory infertility. It is prudent to think that the obesity crisis in this country is changing the rates of infertility and subfecundity. These rates are difficult to assess, but the current best estimates are that 6% of married women 15 to 44 years of age in the United States are unable to get pregnant after one year of unprotected sex (infertility) and that about 11% of all women ages 15 to 44 in the United States have difficulty getting pregnant or carrying a pregnancy to term (impaired fecundity). Population studies have shown that approximately 30% of overweight and obese women have PCOS and that the condition is present in 5% of normal-weight women. In cases of ovulatory infertility, 90% are a result of PCOS. As previously mentioned, the CDC (2011-2012) reported that 69% of the population in the United States is overweight or obese, which means that out of 100 000 reproductive-aged women, 69,000 are overweight or obese and 30% (20,700) of those women will have PCOS. That means that 20.7% of adult women have an impaired capacity to become pregnant secondary to oligo or anovulation. Obese women who receive donor eggs from normal-weight women are also 23% less likely to have successful implantation, 19% less likely to have a clinical pregnancy, and 27% less likely to have a live birth.13 But even in ovulatory obese women, they are less likely to conceive, their oocyte and embryo quality are reduced, and they have impaired endometrial receptivity. Poor oocyte and embryo quality and impaired endometrial receptivity are likely secondary to oxidative stress. Oxidative stress is defined as an imbalance between pro-oxidant molecules including reactive oxygen species and antioxidant defenses. Oxidative stress has been linked to several reproductive diseases, including endometriosis, PCOS, and unexplained infertility—as well as pregnancy complications such as miscarriage, preeclampsia, and intrauterine growth restriction. It appears that excessive reactive oxygen species production overpowers the body’s natural antioxidant defense system, creating an environment unsuitable for normal female physiologic reactions that are requisite for successful reproduction. Dietary behaviors resulting in obesity and malnutrition are linked with oxidative disturbances and chronic, low-grade inflammation. Studies have shown, repeatedly, that animal foods, and their accompanying saturated fats, trans fats, arachidonic acids, cholesterol, and proteins, are associated with systemic inflammation. Highly refined carbohydrates have also been implicated in the causation of inflammation. The data are also clear that whole, minimally processed or unprocessed plant foods are anti-inflammatory in nature. According to data from the 2009 US Department of Agriculture (USDA) Economic Research Service, the composition of American diet consists of 25% animal foods, 63% processed food, and only 12% plant foods (www.ers. usda.gov/publications/EIB333). The result of this diet is an obese female population that is oligo or anovulatory with oxidative stress, a reduced capacity to become pregnant, because of infrequent ovulation, an egg or embryo of poor quality, and a hostile in utero environment.
Declining Sperm and Semen Quality
Oxidative stress and dietary patterns not only affect the reproductive capacity of women but also affect sperm and semen quality. Male factors are identified in 40% to 60% of cases of couples with infertility. Smoking, alcohol, excessive marijuana, and heat exposure to the testes have all been implicated, but diet plays a huge role in the quality of semen and sperm. Studies reveal that saturated fat consumption negatively affects both sperm counts and sperm concentration in a dose–responsive fashion. In contrast, sperm morphology is positively influenced by a higher intake of omega-3 fats. There is a general consensus that semen quality has been in decline in several areas of the world over the past 50 years. This decline is thought to be secondary to a global change in environmental exposures. Specific macronutrients in food, like saturated fat, can negatively affect sperm and semen quality, but food is, in many cases, the vector for other environmental pollutants and endocrine disruptors that are affecting male reproductive capacity. A mother’s consumption of beef can negatively affect her son’s sperm quality as an adult. Perinatal dioxin exposure can also permanently impair semen quality. Presumptively, the maternal beef consumption and dioxin exposure, resulting in reduced semen quality in male offspring, has to do with the endocrine disrupting nature of hormones that are given to cattle during the farming of these animals, and the endocrine disrupting nature of dioxins. Six hormones are commonly used in Canadian and American beef production, which include both natural and synthetic estrogens, androgens, and progesins. Dioxins are a group of compounds that are considered persistent environmental pollutants and are found throughout the environment. They are lipophilic compounds, so they accumulate in the food chain, mainly in the fatty tissue of animals. More than 90% of human dioxin exposure is through food, mainly meat, dairy, fish, and shellfish. These studies represent a small sample of all the studies that show the negative impact of animal food consumption on the quality of semen and sperm. It is clear that both men and women would benefit from a diet high in antioxidants and low in saturated fat and contaminated animal foods to improve the opportunity for conception and live birth.
Article Review
Nutriepigenomics
The Impact of Nutrition and Environmental Epigenetics
Nutrition During Pregnancy Impacts Offspring’s Epigenetic Status—Evidence from Human and Animal Studies
The Impact of Nutrition and Environmental Epigenetics
Nutrition During Pregnancy Impacts Offspring’s Epigenetic Status—Evidence from Human and Animal Studies
Video Review
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Unit Task
- Conduct an interview and assessment with at least two pregnant women. Evaluate and document their lifestyle practices using the forms you've been using from the previous tasks. Start providing information about epigenetics and pregnancy. Create a written summary of your activity and include the personal reflection (verbatim) of your clients.
- Submit your Reflective Journal after watching the videos, reading the lesson and article.