Reproduction is controlled by hormones, and hormones work at very low concentrations. This makes the reproductive system a sensitive target for substances in the environment that interfere with hormone signalling. Over recent decades, research on these so-called endocrine-disrupting chemicals has grown into a major field, spanning toxicology, epidemiology, wildlife biology and regulation.
The archive behind this page covers a broader idea of “environment” as well: heat, radiation, social conditions and maternal nutrition all appear alongside industrial chemicals such as phthalates and pesticides. This overview concentrates on chemical exposures, where the scientific and regulatory debate has been most intense.
What is an endocrine disruptor?
The Endocrine Society, a professional body for hormone specialists, defines an endocrine-disrupting chemical as an external chemical, or mixture of chemicals, that interferes with any aspect of hormone action. Such substances can mimic natural hormones, block their receptors, or alter how hormones are made, transported or broken down. Examples studied in reproductive research include the synthetic oestrogen diethylstilbestrol (DES), once given in pregnancy, the plastics chemical bisphenol A (BPA), phthalates used to soften plastics, and certain pesticides and fungicides.
A joint report by WHO and the UN Environment Programme in 2012 stressed that endocrine systems are very similar across vertebrate species. Effects seen in wildlife or laboratory animals may therefore also occur in humans if exposure happens at a vulnerable time and at concentrations high enough to alter hormonal regulation.
Why timing matters
A central idea in the field is that the same exposure can have very different consequences depending on when it happens. The WHO/UNEP report was particularly concerned with effects on early development, which can be irreversible and may not become apparent until later in life. The Endocrine Society’s 2015 scientific statement reviewed evidence in male and female reproduction among other areas, noting for example that exposure to DES in the womb raised the risk of undescended testes in boys.
Some research goes further and asks whether effects can be passed to later generations through epigenetic changes, chemical marks on DNA that alter how genes are used without changing the genetic sequence. The same statement explains that a true transgenerational effect must be seen in the great-grandchildren of an exposed pregnant animal, because the fetus and its own germ cells are directly exposed. It also cautions that some of the best-known animal studies used high doses and need to be repeated at levels relevant to people, and that causality in humans must be inferred with care.
Among the animal findings it describes, prenatal exposure of rats to the phthalate DEHP was followed by delayed puberty and lower sperm counts in the third generation, and DEHP exposure also altered DNA methylation in the testis.
How the evidence is gathered
Evidence on endocrine disruptors comes from three broad sources: experiments in cells and laboratory animals, observations in wildlife, and epidemiological studies of human populations. Each has limits. Animal experiments can establish cause and effect but may use doses or exposure routes unlike those of people, and differences in how such studies are run make broad conclusions difficult. Human studies measure real-world exposures but can usually show only associations. The Endocrine Society’s statement argued that, for several reproductive outcomes, the animal evidence for causal links is consistent with the correlations seen in people, while still urging caution before concluding that a chemical causes a given effect in humans.
The sperm count debate
Concern about human reproductive health reached a wide audience in 1992, when a review in the BMJ analysed 61 studies of nearly 15,000 men published between 1938 and 1991. It reported that average sperm concentration had fallen from 113 million per millilitre in 1940 to 66 million per millilitre in 1990. The authors linked the trend to a parallel rise in genital abnormalities such as testicular cancer. Later work grouped poor semen quality, testicular cancer and other male disorders as possible signs of a common problem in fetal development, discussed on the page on the testis and spermatogenesis.
A much larger meta-analysis in 2017 included 185 studies of almost 43,000 men who gave samples between 1973 and 2011. It reported a decline of 50 to 60% in sperm counts among men from North America, Europe, Australia and New Zealand who had not been selected on the basis of their fertility. The authors called for urgent research into the causes.
The interpretation remains disputed. Critics have argued that sperm count varies widely between individuals and populations for many reasons, much of that range is not a sign of disease, and a falling average does not by itself show that male fertility is declining or identify a cause.
From the laboratory to regulation: the case of bisphenol A
Bisphenol A shows how scientific assessments can change. In 2015 the European Food Safety Authority (EFSA) set a temporary tolerable daily intake for BPA of 4 micrograms per kilogram of body weight. Its 2023 re-evaluation set a new tolerable daily intake of 0.2 nanograms per kilogram, a value 20,000 times lower. The critical effect chosen was on the immune system rather than on reproduction, although reproductive and developmental effects were among the other health effects assessed. EFSA concluded that estimated dietary exposure in all age groups exceeded the new limit by two to three orders of magnitude, indicating a health concern.
What is established and what is still debated
- Established: some chemicals interfere with hormone systems; hormone systems are shared across vertebrates; exposures during development can have lasting effects in animals; and some exposures, such as DES in pregnancy, have clearly harmed human reproductive health.
- Debated: how large the effects of everyday low-level exposures are in people; whether falling average sperm counts mean falling fertility; how often effects pass to later generations in mammals; and how to regulate mixtures of many chemicals at low doses.
This page summarises scientific reviews and official assessments. It is not medical or regulatory advice.
Sources
- WHO / UNEP, State of the science of endocrine disrupting chemicals 2012
- Gore AC et al., Endocrine Reviews, 2015 — EDC-2: the Endocrine Society’s second scientific statement on endocrine-disrupting chemicals (doi:10.1210/er.2015-1010)
- Carlsen E, Giwercman A, Keiding N, Skakkebaek NE, BMJ, 1992 — Evidence for decreasing quality of semen during past 50 years (doi:10.1136/bmj.305.6854.609)
- Levine H et al., Human Reproduction Update, 2017 — Temporal trends in sperm count: a systematic review and meta-regression analysis (doi:10.1093/humupd/dmx022)
- Boulicault M et al., Human Fertility, 2022 — The future of sperm: a biovariability framework for understanding global sperm count trends (doi:10.1080/14647273.2021.1917778)
- EFSA CEP Panel, EFSA Journal, 2023 — Re-evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs (doi:10.2903/j.efsa.2023.6857)
References from the journal archive
These articles were published in Reproduction, the Journal of Reproduction and Fertility or Reviews of Reproduction and are still cited at their old addresses on this domain. Each link leads to the publisher’s version through its DOI.
- BABOON MENSTRUAL CYCLES AFFECTED BY SOCIAL ENVIRONMENT
- EFFECTS OF α-CHLOROHYDRIN AND RELATED COMPOUNDS ON THE REPRODUCTIVE ORGANS AND FERTILITY OF THE MALE RAT
- THE ENTRY OF α-CHLOROHYDRIN INTO BODY FLUIDS OF MALE RATS AND ITS EFFECT UPON THE INCORPORATION OF GLYCEROL INTO LIPIDS
- Use of a xanthine oxidase free radical generating system to investigate the cytotoxic effects of reactive oxygen species on human spermatozoa
- Environmental oestrogens--present understanding
- Effects of an organophosphate pesticide, quinalphos, on the hypothalamo-pituitary-gonadal axis in adult male rats
- Retention of cytoplasmic droplet by rat cauda epididymal spermatozoa after treatment with cytotoxic and xenobiotic agents
- Delayed effect of heat stress on steroid production in medium-sized and preovulatory bovine follicles
- Effects of nutrition and environmental factors on the fetal programming of the reproductive axis
- Fetal endocrinology and development--manipulation and adaptation to long-term nutritional and environmental challenges
- Improvement of semen quality by nocturnal scrotal cooling and moderate behavioural change to reduce genital heat stress in men with oligoasthenoteratozoospermia
- Relationship between maternal endocrine environment, early embryo development and inhibition of the luteolytic mechanism in cows
- The impact of endocrine disruptors on oocyte competence
- Environmental anti-androgens and male reproductive health: focus on phthalates and testicular dysgenesis syndrome
- Hoechst 33342 stain and u.v. laser exposure do not induce genotoxic effects in flow-sorted boar spermatozoa
- Alterations in follicular dynamics and steroidogenic abilities induced by heat stress during follicular recruitment in goats
- Heat stress diminishes gonadotropin receptor expression and enhances susceptibility to apoptosis of rat granulosa cells
- Impact of a mild scrotal heat stress on DNA integrity in murine spermatozoa
- Molecular interactions of the aryl hydrocarbon receptor and its biological and toxicological relevance for reproduction
- Factors affecting birth weight in sheep: maternal environment
- Reduced embryonic survival in rainbow trout resulting from paternal exposure to the environmental estrogen 17α-ethynylestradiol during late sexual maturation
- A single, mild, transient scrotal heat stress causes DNA damage, subfertility and impairs formation of blastocysts in mice
- Mono-(2-ethylhexyl) phthalate stimulates basal steroidogenesis by a cAMP-independent mechanism in mouse gonadal cells of both sexes
- Preimplantation embryo programming: transcription, epigenetics, and culture environment
- Transgenerational epigenetic effects of the endocrine disruptor vinclozolin on pregnancies and female adult onset disease
- Induction of spermatogenic cell apoptosis in prepubertal rat testes irrespective of testicular steroidogenesis: a possible estrogenic effect of di( n -butyl) phthalate
- Transgenerational effects of the endocrine disruptor vinclozolin on the methylation pattern of imprinted genes in the mouse sperm
- Bovine blastocysts with developmental competence to term share similar expression of developmentally important genes although derived from different culture environments
- In vitro growth and steroidogenesis of dog follicles are influenced by the physical and hormonal microenvironment
- Differences in the metabolomic signatures of porcine follicular fluid collected from environments associated with good and poor oocyte quality
- Adverse prenatal environment and kidney development: implications for programing of adult disease
- Age, the environment and our reproductive future: bonking baby boomers and the future of sex
- Bisphenol A modulates the metabolic regulator oestrogen-related receptor-α in T-cells
- Concerns about the widespread use of rodent models for human risk assessments of endocrine disruptors
- Current exposure of 200 pregnant Danish women to phthalates, parabens and phenols
- Insulin-like factor 3 as a monitor of endocrine disruption
- Late-life effects on rat reproductive system after developmental exposure to mixtures of endocrine disrupters
- Low-dose effects of bisphenol A on early sexual development in male and female rats
- Semen quality trends in French regions are consistent with a global change in environmental exposure
- Sex-specific Esr2 mRNA expression in the rat hypothalamus and amygdala is altered by neonatal bisphenol A exposure
- Bisphenol A modulates receptivity and secretory function of human decidual cells: an in vitro study
- Effects of neonatal exposure to a glyphosate-based herbicide on female rat reproduction
- HLA-G and CD8+ regulatory T cells in the inflammatory environment of pre-eclampsia
- The effects of radiofrequency electromagnetic radiation on sperm function
- Prenatal exposure to paracetamol/acetaminophen and precursor aniline impairs masculinisation of male brain and behaviour
- Very low doses of heavy oxygen ion radiation induce premature ovarian failure