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Reproductive Health Research and Resources

image from Andy445 at iStock

In considering reproductive health, we focus especially on exposures to environmental contaminants, particularly during critical periods of development. We also note other important factors that can influence reproductive health outcomes, such as nutrition and stress.

On this page, you will learn what the emerging science says about links between these exposures and all aspects of reproductive health—conception, fertility, pregnancy, adolescent development and adult health.1 Environmental impacts can be life-long or even passed on to future generations.

Environmental Contributors

Reproductive Toxicants

Exposure to environmental toxicants is linked with various reproductive diseases and disorders, many of which harm a person’s ability to conceive and complete a successful pregnancy.

Toxicants and their reproductive health effects are grouped by the strength of evidence (strong or good). Unless noted otherwise, toxicants are from CHE's Toxicant and Disease Database.2  

Associations of Adverse Reproductive Effects and Toxicants

Reproductive Effects

Strong Evidence

Good Evidence

Abnormal sperm (morphology, motility, and sperm count)

1,1-dichloroethane
Ethylene glycol ethers
Heat
Ionizing radiation
Lead
Microwave radiation

Pesticides, including chlordecone, dibromochloropropane (DBCP), ethylene dibromide (EDB)

2-Bromopropane
Carbon disulfide

Electromagnetic radiation3
Estrogens / DES
Gossypol
PCBs (polychlorinated biphenyls)
Pesticides, including 2,4-D, alachlor, atrazine, benomyl, diazinon and molinate
Tobacco smoke (active smoking)

Adverse ovarian effects

 

Vinyl cyclohexene dioxide

Adverse testicular effects

Estrogens / DES

Solvents, including ethyl alcohol (ethanol), glycol ethers and nitrobenzene

Di (2-ethylhexyl) phthalate (DEHP)/MEHP
Ethyl tert butyl ether
Hexafluoroacetone
Phenylphosphine
Vinyl cyclohexene dioxide

Altered sex ratio

 

Boron
Dioxins / TCDD

Mercury

Pesticides, including dibromochloropropane (DBCP) and fungicides

PCBs4
Altered time to sexual maturation (accelerated or delayed puberty)

Estrogens / DES

Phthalates5

Flame retardants6

Lead

Tobacco7
Early onset menopause   Tobacco smoke (active smoking)
Ectopic pregnancy Tobacco smoke8  
Endometriosis   

DES9

PCBs

Erectile dysfunction  

B-dimethylaminopropionitrile (DMAPN)

Carbon disulfide

Fetotoxicity (miscarriage / spontaneous abortion, stillbirth) Anesthetic gases
Ethyl alcohol (ethanol)
Ethylene glycol ethers
Ethylene oxide
Ionizing radiation
Nicotine
Tobacco smoke

Air pollution, including carbon monoxide and particulate air pollution (soot)
Bisphenol A
Carbon disulfide
Chlorination byproducts / trihalomethanes
Chloroform
DES
Formaldehyde
Metals, including arsenic, lead and mercury
Methyl isocyanate
N-methylpyrrolidone (NMP)
Nitrogen dioxide

PCBs10
Pesticides, including DDT/DDE, dibromochloropropane (DBCP), dithiocarbamates, fungicides, glyphosate, herbicides, hexachlorobenzene, phenoxyacetic herbicides, organochlorine pesticides, paraquat and triazene herbicides
Solvents, including 1,1,1-trichloroethane, methylene chloride, tetrachloroethylene (PCE), toluene, trichloroethylene (TCE) and xylene
Sulfur dioxide
Tobacco smoke (secondhand)

Genito-urinary malformations (either male or female) DES

Pesticides, including molinate

Phthalates,11 includng di (2-ethylhexyl) phthalate (DEHP)/MEHP

Tobacco smoke

Hormonal changes (levels of circulating sex hormones—FSH/LH, Inhibin, and/or estrogens, progesterones, androgens, prolactin) Dibromochloropropane (DBCP)
Ethyl alcohol (ethanol)

2-bromopropane
Dioxins / TCDD
Metals, including cadmium and lead
Pesticides, including fungicides, methamidophos organophosphates, parathion and vinclozolin
Phthalates
Solvents, including toluene and xylene
Tobacco smoke (active smoking and secondhand)
Vinyl chloride

Low birth weight / small for gestational age / intrauterine growth retardation 1,1-dichloroethane
Cocaine
Ethyl alcohol (ethanol)
Nicotine
Tobacco smoke, including secondhand

Air pollution, including carbon monoxide and particulate air pollution (soot)

Bisphenol A12

Brominated flame retardants13

Chlorination byproducts (trihalomethanes)
DES
Metals, including arsenic, lead and mercury

Methamphetamine14

Noise
PCBs
Pentachlorophenol (PCP)

Perfluorinated compounds,15 including PFOA16
Pesticides, including atrazine, chlorpyrifos, cyanazine, DDT/DDE, diazinon, herbicides, lindane, metolachlor, organochlorine pesticides and organophosphates

Solvents, including toluene

Menstrual disorders (abnormal bleeding, short cycles, long cycles, irregular cycles, painful periods) Ionizing radiation

2-bromopropane

Chlorination byproducts (trihalomethanes)
Dioxins / TCDD
Estrogens / DES
Formaldehyde
Metals, including lead and mercury
PCBs
Pesticides, including atrazine, chlordecone, DDT/DDE, fungicides, herbicides, hexachlorobenzene, lindane, mancozeb, maneb, organochlorine pesticides, organophosphates and toxaphene
Solvents, including benzene, carbon disulfide, ethyl alcohol (ethanol), tetrachloroethylene (PCE), toluene and xylene
Tobacco smoke (secondhand)

Ovarian atrophy   1,3-butadiene
Polycystic ovary syndrome (PCOS)  

Bisphenol A17

Pre-eclampsia (pregnancy-induced hypertension)  

Chloroform

Solvents

 

Preterm delivery Tobacco smoke (active smoking and secondhand)

Air pollution, including carbon monoxide and particulate air pollution (soot)

Benzene

DDT/DDE

DES

Ethylene oxide

Lead

Reduced fertility—female (infertility and subfertility)

Anesthetic gases

Estrogens / DES

Ionizing radiation

Tobacco smoke (active smoking)

2-bromopropane
Ethylene glycol ethers
Formaldehyde
Lead
Nitrous oxide
Pesticides
Solvents, including 1-bromopropane, tetrachloroethylene (PCE) and toluene
Tobacco smoke (secondhand)

Reduced fertility—male (infertility and subfertility)

1,1-dichloroethane
2-bromopropane
Estrogens / DES
Heat
Ionizing radiation
Lead
Pesticides, including chlordecone, dibromochloropropane (DBCP), ethylene dibromide (EDB)
Solvents, including carbon disulfide, ethyl alcohol (ethanol) and ethylene glycol ethers

Cadmium
Radar
Solvents, including 1-bromopropane, methylene chloride and tetrachloroethylene (PCE)
Tobacco smoke (active smoking and secondhand)
Welding fumes

Reproductive tract toxicity, female  

4-vinylcyclohexene

Reproductive tract toxicity, male Dichloroacetic acid

1,3,5-triglycidyl-s-triazinetrione
2-chloropropionic acid
4-vinylcyclohexene
Diglycidyl ether
Ethyl tert butyl ether
n-Butyl glycidyl ether
Phenyl glycidyl ether

The following toxicants are associated with unspecified disorders and conditions:

Female reproduction:
  • chromium (VI) (good evidence)

Male reproduction:

  • 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) (strong evidence)
  • Chromium (VI) (good evidence)
  • Methyl chloride (good evidence)
  • Methyl n-butyl ketone (good evidence)

 Notes:

  • The research on these and other toxicants is rapidly expanding and being updated.
  • Reproductive effects may result from exposures before conception, as a fetus, as an infant or child, during puberty, or as an adult.
  • More information about the links between toxicants and reproductive health, including links with more limited evidence, are in CHE's Toxicant and Disease Database.

Nutrition and Birth Outcomes

Nutritional Recommendations

Birth outcomes are affected by protein, energy (calories) and micronutrient intake. These levels are recommended during pregnancy to reduce adverse birth outcomes and promote both fetal and maternal health:18

  • Energy: 2,200-2,900 calories
  • Protein: 71 grams
  • Lysine: 51 mg/kg
  • Omega-3 fatty acids: 1.4 grams
  • Iron: 27 mg
  • Folate: 800 µg
  • Calcium: 1000-1300 mg
  • Vitamin D: 600 IU

Poor maternal nutrition can affect birth outcomes, but the relationship between the two is also influenced by characteristics that vary among populations, including demographic factors, socioeconomic status and genetic drivers. Improving nutritional status is known to reduce mortality, morbidity, and health-care costs associated with adverse pregnancy outcomes, including low birth weight, preterm birth and intrauterine growth restriction (IUGR). Aside from pregnancies with congenital anomalies, these three outcomes are the leading causes of neonatal death, and all three can result in a predisposition to chronic disease in adulthood. Nutritional status and low birth weight are especially important in developing countries where 98 percent of all neonatal deaths occur. Improved nutrition in nutrient-deficient mothers is accompanied by a corresponding reduction in adverse birth outcomes.19

Poverty and Other Stressful Environments

Low-income families are more likely to experience nutritional deficiencies and, especially in developing countries, preterm birth, low birth weight and IUGR outcomes. Low-income status is also associated with other factors that are associated with poor birth outcomes, such as smoking, alcohol and substance abuse, infections and a history of preterm births. It is unclear how these factors interact with low nutritional status.20

Pregnant women with high stress and anxiety levels are at increased risk for miscarriage, preeclampsia (a serious pregnancy complication characterized by high blood pressure and signs of damage to kidneys or other organ systems),21 preterm labor, fetal growth restriction (related to low birth weight) and birth defects.22

Health Conditions and Pregnancy

Before Pregnancy

Many pre-conception maternal health conditions are associated with poor birth outcomes. They include these, all from the US Office of Women's Health unless noted otherwise:23

Maternal Health Condition Potential Impact on the Pregnancy
Asthma Increased risk of preeclampsia, poor weight gain in the fetus, preterm birth or cesarean birth
Depression Increased risk for postpartum depression
Diabetes Alterations in organ development or growth restriction in the fetus24
Eating disorders Increased risk of birth defects, premature birth and postpartum depression
Epilepsy and other seizure disorders Increased increase the risk of miscarriage or stillbirth
High blood pressure Increaseed risk of preeclampsia, placental abruption (separation of the placenta from the wall of the uterus), preterm birth and low birth weight
Overweight and Obesity Increased risk of preeclampsia and preterm delivery
Sexually transmitted infections Increased risk of early labor, low birth weight, birth defects and stillbirth
Thyroid disease Increased risk of poor weight gain in the fetus or birth defects
Uterine fibroids Increased risk of preterm or breech birth or cesarean delivery

During Pregnancy

Several maternal health conditions during pregnancy increase the risk for poor birth outcomes.25

Maternal Health Condition  Potential Impact on the Pregnancy 
Hypertension Increased risk of preclampsia, gestational diabetes, preterm birth, small infants for gestational age, placental abruption and infant death
Gestational diabetes mellitus (GDM) Increased risk of preeclampsia, early delivery, cesarean birth, complications during pregnancy, infant breathing problems, infant blood sugar problems, and jaundice
Obesity Increased risk of preeclampsia, gestational diabetes mellitus, stillbirth and cesarean delivery

Chronic Disease, Infertility and Pregnancy Loss

Autoimmune Conditions Affecting Fertility

Autoimmune conditions have the potential to impact fertility by causing reproductive organs to fail or inhibiting the ability of a fertilized egg to implant; they may even cause pregnancy loss.29

Though causal links have not been identified, between 10 and 30 percent of women with premature ovarian failure also have an autoimmune disease. In males, autoimmune orchitis (inflammation of the testes) can cause infertility.30

Other examples of chronic diseases and conditions that can contribute to infertility are cancer,31 chronic kidney disease,32 inflammatory bowel disease (IBD)33 and obesity.34

Infection and Infectious Disease

Mycoplasma genitalium is a pathogenic bacterium that may be sexually transmitted; it is easily treated with antibiotics. A two-fold increase in the risk of pelvic inflammatory disease, preterm birth and spontaneous abortion is seen with M. genitalium infection.35 Other examples of infectious diseases and infections that can contribute to pelvic inflammatory disease and infertility are Chlamydia trachomatis,36 gonorrhea37 and Trichomonas vaginalis.38 More information about infection and pregnancy outcomes is available on our Global Environment page and from the US Office of Women's Health.

Timing of Exposures

The developmental stage of an individual at the time of an exposure can make a huge difference in the outcome. An exposure that could cause severe malformations for a fetus could be harmless to an individual later in life. In general, exposures early in life (embryo, fetus, infant and child) and again during puberty are more likely to cause harm to the developing and maturing reproductive system than exposures at other times. However, because hormone levels fluctuate throughout life and regulate many reproductive functions, substances and exposures that impact our hormones can have effects throughout our reproductive lives.

fetus

image from lunar caustic at Creative Commons

Critical windows.  According to the World Health Organization, a critical window of susceptibility is a "sensitive time interval during development when environmental exposures can interfere with physiology of cell, tissue, or organ." These windows include periods in which cells are growing rapidly, tissues are forming, and the young body is still without most protective capabilities, such as an immune system, blood brain barrier, or DNA repair system.  

The Critical Windows of Development39 timeline from the Endocrine Disruption Exchange40 shows how exposures to certain chemicals can affect different anatomical systems (including reproductive and endocrine systems) at different stages of prenatal development.

Genetics and Infertility

Genetic Conditions Associated with Infertility41
  • Klinefelter syndrome (male)
  • 47,XYY syndrome (male)
  • 47,XXX syndrome (female)
  • Turner syndrome (female)
  • Structural chromosomal abnormalities (male)
  • Y chromosome microdeletions (male)
  • Robertson Translocations (male)
  • Genomic copy number variants (female and male)
  • Single-gene disorders (female and male)
  • Epigenetic and posttranscriptional modification (female and male)
  • Primary Ovarian Failure (female)
  • Uterine fibroids (female)
  • Endometriosis (female)

Studying the genetics of infertility is a large endeavor: There are around 2,300 genes expressed in the testis alone. That said, up to 50 percent of infertility cases may be caused by genetic errors including sickle cell anemia and fragile X syndrome. Mutations in genes involved in steroid synthesis and energy pathways can also cause infertility.

Genetically caused infertility can arise from more than just single gene errors. Alterations in chromosomes, the number of gene copies and epigenetic disorders can all impact fertility.42 More information about genetics is on our Gene-Environment Interactions webpage.

Pregnancy and the Environment

pregnant woman and partner

image from Dr Dawn Tames at Creative Commons

“Women are the first environment. We are an embodiment of our Mother Earth. From the bodies of women flows the relationship of the generations both to society and the natural world.”

  -Katsi Cook, Mohawk midwife and reproductive justice activist

As Cook states, mothers embody their relationships with the environment in a number of ways:

  1. Many environmental toxicants, such as lead and PCBs, can accumulate in a mother’s body over time, both prior to and during pregnancy. These toxicants may then be passed down to her children through her blood and breast milk.
  2. Stress responses and some chemicals can induce changes in a mother’s genetic makeup, which can also be passed on to future generations. See Gene-Environment Interactions.
  3. Early exposures (in utero, in infancy, in adolescence) that impact a woman’s reproductive health can impact her pregnancy outcomes.

As such, a mother’s health before, during, and after pregnancy are all crucial in determining the health of her child. Environmental exposures that happen at all stages in a woman’s life are relevant to pregnancy.

Pregnancy Complications

Complications during pregnancy can have pervasive and long-lasting health impacts on the child. Adverse pregnancy outcomes such as miscarriage, stillbirth, and birth defects can be a deeply traumatic experience for expecting parents, and can also pose a physical threat to mothers. Pregnancy outcomes are the results of genetic, endocrine, behavioral, and/or environmental factors.

Some chemicals and other types of environmental toxicants can impact fetal health and are called fetotoxicants. Environmental exposures can also impact fetal growth and can contribute to pregnancy loss/fetal death. We do not discuss birth defects, other than defects of reproductive tracts, nor cancers of the reproductive system on this page; see separate pages on Birth Defects and Cancer.

Impaired Fetal Growth, Low Birth Weight, and Preterm Birth

Little Things Matter: The Impact of Toxins on Preterm Birth from Bruce Lanphear on Vimeo.

Impaired fetal growth43 includes low birth weight and small for gestational age (SGE). Impaired fetal growth can lead to an increased risk of many childhood and adult illnesses.44

Impaired fetal growth often coincides with preterm birth,45 the birth of an infant before 37 weeks of pregnancy. In 2013, about one in nine births in the United States was preterm, with slightly lower rates with white births and higher rates with black and Hispanic births.46 Preterm birth is the greatest contributor to infant death and a leading cause of long-term neurological disabilities in children.47 Preterm birth is also associated with a number of other health issues.

Pregnancy Loss (Miscarriage, Stillbirth)

In the United States, both miscarriage and stillbirth refer to the unplanned loss of a pregnancy, with miscarriage at less than 20 weeks of pregnancy and stillbirth at 20 or more weeks of pregnancy.48 Among women with a known pregnancy, 15 to 20 percent will have a miscarriage, while about one percent will experience a stillbirth.49

Miscarriages and stillbirths may occur for many reasons:

  • The egg or sperm may be damaged, making fertilization difficult or impossible and/or preventing the fertilized egg from surviving afterwards.
  • A problem may exist in the hormone balances needed to maintain the pregnancy.
  • The fetus may not have developed normally.
  • Physical problems may exist with the uterus or cervix.50

Ectopic Pregnancy

In an ectopic pregnancy, a fertilized egg implants in the mother's body somewhere other than the main cavity of the uterus.51 Often, the egg implants in a fallopian tube, which is known as a tubal pregnancy. This situation can be dangerous to the mother, and the embryo will not be able to survive.

Issues in Fertility and Sexual Health

sperm and egg

image from Andrea Laurel at Creative Commons

Infertility is the inability to conceive after one year of unprotected sex.52 While an increase in infertility, especially in industrialized nations, has been reported, changing social and behavioral variables—such as increased access to contraception, economic improvements, improved social standing of women, and delayed marriage—make conclusions difficult.53 Some researchers suggest that lifestyle changes in industrialized nations, accompanied by a gradual increase in the number and amount of environmental toxicants people are exposed to over the years, could contribute to overall decreases in fertility.54

While fertility is influenced by many factors—including aging, acute and chronic diseases, treatments for certain conditions, and behavior—environmental toxicants are known or suspected to affect fertility in both men and women. Here we focus on common diseases and disorders of the female and male reproductive tracts with good or strong links to environmental toxicants.

Diseases and Disorders of the Female Reproductive System

Endometriosis occurs when the tissue that lines the inside of the uterus (the endometrium), or endometrial-like tissue, grows outside the uterus on other parts of the body. This condition affects between 10 and 15 percent of reproductive-age women and is one of the leading causes of infertility, with about 30 to 40 percent of those affected being infertile.55

Uterine fibroids (leiomyoma) are made of muscle cells and other tissues that grow in and around the wall of the uterus and can cause pelvic pain, abnormally heavy periods, abnormal uterine bleeding, infertility and complications in pregnancy.56 This condition occurs in 25 to 50 percent of all women, with some estimates even higher.

Polycystic ovarian syndrome (PCOS) is characterized by irregular periods, androgen excess, pelvic pain, and ovarian cysts. By some measurements, the prevalence of PCOS is as high as 15 to 20 percent of women. Women with PCOS have a higher risk of developing diabetes, endometrial cancer, infertility, miscarriage, and high blood pressure.57

Early onset menopause is menopause before age 40. Some medical treatments can cause early menopause, including chemotherapy or pelvic radiation treatments for cancer, surgical removal of both ovaries, and hysterectomy (removal of the uterus). Some autoimmune diseases can lead to early menopause, and there may be genetic factors, also. Besides reduced or eliminated fertility, early onset menopause can also increase a woman's risk of osteoporosis and heart disease.58

Menstrual disorders include amenorrhea (lack of a period), dysmenorrhea (painful periods), and abnormal uterine bleeding. Amenorrhea is normal and expected during pregnancy and lactation (breastfeeding), but at other times may indicate a medical condition needing attention. Some conditions that can lead to amenorrhea include extreme weight loss, eating disorders, excessive exercising, and stress. Dysmenorrhea may be caused by uterine fibroids or endometriosis, especially in older women. Abnormal uterine bleeding may be caused by hormonal changes, although more serious underlying medical conditions can also cause abnormal bleeding.59

Diseases and Disorders of the Male Reproductive System

Hypospadias is a birth defect in boys where the opening of the urethra (the tube that carries urine from the bladder to the outside of the body) is not located at the tip of the penis. The abnormal opening can form anywhere from just below the end of the penis to the scrotum. It is estimated that about five out of every 1,000 boys born in the United States have hypospadias, making it one of the most common birth defects.60

Cryptorchidism, or undescended testicles, occurs when one or both testicles do not drop down into the scrotum before birth. It is the most common genital problem in pediatrics.61 About one third of premature boys have an undescended testicle on at least one side, compared to two to eight percent of full-terms boys. If left untreated, cryptorchidism can impact the testis over time, reducing spermatogenesis and resulting in reduced fertility in adulthood.62

Erectile dysfunction, or ED, is the consistent or recurrent inability to attain and/or maintain a penile erection sufficient for sexual performance.63 Many factors can increase risks for ED, including these:64

  • aging, although aging itself does not cause ED
  • being overweight
  • injuries, including from prolonged bicycling
  • some medications, including blood pressure medications, antihistamines, antidepressants, tranquilizers, appetite suppressants, and ulcer medications
  • stress, depresson or other psychological states
  • drug or alcohol use
  • sex hormone levels
  • other medical conditions including hypertension, cardiovascular diseases, atherosclerosis, and diabetes mellitus

Other Areas of Concern in Reproductive Health

Altered Sex Ratio

The ratio of male to female offspring at birth is typically 104 to 107 boys for every 100 girls, excluding societies where selective abortion skews the sex ratio. Anything outside this range is considered an altered sex ratio. Although research is fairly limited, some studies have found associations between certain chemicals and altered sex ratio. Because many of these chemicals affect fertility, departures from this fairly stable ratio could reflect damage to reproductive systems beyond the altered sex ratio.

Timing of Puberty Onset in Girls

The age of puberty onset appears to have declined in several industrialized nations over the last half century. In the United States, girls get their first periods (menarche) a few months earlier than they did 40 to 50 years ago, and they develop breasts (thelarche) one to two years earlier.65 The hormonal cues that initiate the onset of puberty are sensitive to a variety of influences, including obesity, nutrition, and stress, as well as exposure to environmental pollutants.66

Breastfeeding

breast feeding

image from Mellssa Segal at Creative Commons

Hormone levels during puberty, pregnancy and lactation regulate the development of breast tissue and the ability to produce sufficient milk for an infant. The mother's states of well-being, including stress, fatigue, and nutrition, are known to affect milk production.67 Obesity may also impact the initiation and duration of lactation, as can race, age, marital status, education, and socioeconomics.68

The numerous health benefits of breastfeeding are well documented:

  • Babies who are breastfed tend to have higher IQs than babies who are not breastfed.
  • Breastfeeding lowers the risk of death from infectious, gastrointestinal and allergic diseases in babies.
  • Breastfeeding may reduce babies' risk of obesity.69

Mothers also benefit substantially from breastfeeding, with a lower risk of postpartum hemorrhage and depression, as well as reduced blood pressure and stress. Long-term effects include reduced risk of breast and ovarian cancers, hypertension, and type 2 diabetes.70

Unfortunately, in addition to important enzymes and nutrients, breast milk can also carry toxic chemicals, especially persistent organic pollutants (POPs). Chemicals accumulate in a mother’s body throughout her life and can be passed to the baby both through the placenta and in breast milk.

See more about environmental contributors to reproductive health in the list of CHE publications and Dig Deeper resources in the right sidebar.


This page was last revised by Nancy Hepp and student intern Jessica Couch in September 2016. Read about Jessica's internship, including her review summary.

CHE invites our partners to submit corrections and clarifications to this page. Please include links to research to support your submissions through the comment form on our Contact page.

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