Teratogenic and toxic causes of Infertility in animals Infertility is a temporary disturbance in reproductive function wherein the animal cannot become pregnant or cannot conceive. Infertility causes economic losses to the farmers due to delay in maturity, calving and milk production. Teratogens can also be classified as : Physical agents Metabolic conditions Infection Drugs and chemicals. Toxic Agents Causing Infertility In Animals Heavy Metals Organophosphates (Pesticides) Endocrine Disrupting Chemicals (EDCs) Read more in slide share

1. TOXIC AND TERATOGENIC
CAUSES OF INFERTILITY IN
ANIMALS
Prepared by
Group 6

2. INTRODUCTION.
Infertility is a temporary disturbance in reproductive function
wherein the animal cannot become pregnant or cannot conceive.
Infertility causes economic losses to the farmers due to delay in
maturity, calving and milk production.

3. CAUSES OF INFERTILITY:
• Nutritional cause
• Anatomical cause
• Genetic cause
• Bacterial, and viral infections
• Protozoal, fungal, parasitic cause
• Teratogenic, Toxins, and physical cause.

4. TERATOGENIC CAUSE OF INFERTILITY
Teratogens are substances that may produce physical or functional defects in
the animal embryo or fetus or the mother after the pregnant animal is
exposed to the substance.
Exposure to the teratogen affects the fetus or embryo and mother in a variety
of ways, such as the duration of exposure, the amount of teratogenic
substances, and the stage of development, the embryo or fetus is in during
the exposure.

5. Teratogens can also be classified as :
Physical agents
Metabolic conditions
Infection
Drugs and chemicals.

6. Ionizing radiation:
This comes under the physical cause of infertility. Ionizing radiation is radiation
composed of particles like X-rays or gamma rays, that carry adequate energy
to free an electron from an atom or molecule resulting in electrically charged
ions in matter.
By its nature, radiation exposure to a living system of energy sufficient to
produce atomic ionization can damage key cellular molecules and organelles,
especially nuclear and mitochondrial nucleic acids.

7. How it works?
High energy radiation produces single and double-strand breaks in the nucleic acids. The
damaged cellular molecules can result in perturbed cellular function, and altered transcription,
transcription, translation, and reproduction. these perturbations are the root for cellular
genotypic and phenotypic changes that lead to neoplastic transformation.
Recent studies are revealing the possible mechanisms of ionizing radiation-inducing
carcinogenesis.

8. DRUGS AND CHEMICALS
• Drugs like Indomethacin which is a NSAID is also responsible for
casuing infertility.
• In an animal study and three clinical studies it was found that
regular NSAID , intake led to LUF(leutinised unruptured follicle)
syndrome.
• The pharmacological target of NSAID is cyclo-oxygenase (Cox)
which catalyzes the first rate- limiting step in the production of
prostaglandins.
• Cox2 one of the two isoenzymes is active in ovaries during
follicular development.

9. • Its inhibition is thought to cause luteinised unruptured follicle (LUF) syndrome.(an anovulatory
conditon characterized by clinical signs of ovulation but in the absence of follicular rupture and
ovum release.
• Insecticides
• likewise, insecticides which are a heterogeneous group of chemicals are widely used in
agriculture. Insecticide exposure is responsible for ovarian malfunctioning through disruption of
the hypothalamic-pituitary-gonadal axis.
• These insecticides include :
 Organophosphates like chlorpyrifos, Diazinon, malathion etc.

10. Pyrethroids: Permethrin, cypermethrin e.t.c.
Carbamates: Carbaryl, methomyl e.t.c.
• Maximum exposure to these insecticides have some adverse health effect. Reproductive health
is also one of them.
• In females exposure to insecticides leads to reproductive in capacitation primarily through
disturbances in ovarian physiology. Disturbed ovarian activities encompass the alteration in
hormone synthesis, follicular maturation, ovulation process, and ovarian cycle, which will
eventually lead to a decline in infertility, prolonged time to conceive, spontaneous abortion,
stillbirths, and developmental defects.

11. • Pathogensis:
• Insecticide induced ovarian toxicity is operated by endocrine disruption and oxidative stress.
• Oxidative stress occurs due to supression of antioxidant defense system, and increase of reactive oxygen
and nitrogen species, potentiated DNA damage and expression of apoptoic and inflammatory markers.

12. SYMPTOMS
• Failure to conceive
• Early embryonic mortality.
• Abnormalities in fetal development.
• Reduced fertility or sterility.
• Hormonal imbalances.
• Altered sexual behaviour.

13. TREATMENT
• The treatment of teratogens causing infertility in animals
depends on the specific teratogen involved and the extent of
damage caused in some cases the effects of teratogens may be
irreversible
• Prevention and removal of exposure .
• Supportive care and nutrition.
• Hormone therapy.
• Assisted reproductive technique.
• Surgical interventions.

14. TOXIC AGENTS CAUSING INFERTILITY IN
ANIMALS
1. Heavy Metals
2. Organophosphates (Pesticides)
3. Endocrine Disrupting Chemicals (EDCs)

15. HEAVY METALS CAUSING INFERTILITY IN
ANIMALS
• Lead
• Mercury
• Arsenic
• Zinc
• Cadmium
• Copper, etc

16. LEAD TOXICITY
Lead toxicity is a type of metal poisoning that occurs due to exposure to Lead
Sources of lead toxicity
1.Lead-based paint: Ingestion of lead-based paint is the most common cause of lead poisoning in
pets
2.Contaminated materials: Animals may find material contaminated with lead in silage, rubbish
dumps, around farm buildings, and machinery
3.Lead-acid batteries: Lead-acid batteries found on agricultural pasture land are the foremost point
source of lead poisoning in North American cattle
4.Industrial pollution: Gradual poisoning may occur in areas with heavy industrial pollution, where
lead in materials settles in the stomachs of cattle
5.Pica: Young animals and animals with pica, a condition where they eat non-food items, are at a
higher risk of lead poisoning

17. • The exact mechanisms by which lead toxicity affects infertility are not fully understood.
However, research suggests that lead toxicity can impair hormonal synthesis and regulation,
which can lead to reduced fertility in both men and women
• Lead toxicity can induce oxidative stress, which can damage the cells of the reproductive
system
• Lead toxicity can cause inflammation in the reproductive system, which can impair its function
• Moreover, there is evidence that lead exposure can interfere with the sperm acrosome
reaction, which is essential for fertilization and negatively affects outcomes of artificial
insemination
PATHOGENESIS

18. SIGNS AND SYMPTOMS OF LEAD
INFERTILITY
• In men:
• Lead toxicity can reduce the quality of sperm, affect spermatogenesis, and reduce
libido
• Lead toxicity can decrease sperm count and motility, induce abnormal morphology,
and affect functional parameters
• Lead toxicity can impair hormonal synthesis and regulation, which can lead to
reduced fertility
• In women:
• Lead toxicity can cause decreased sexual desire, increased cases of infertility,
spontaneous abortion, menstrual disorders, and stillbirths
• Lead toxicity can impair menstruation, reduce fertility potential, delay conception
time, and impair hormonal production and circulation
• Lead toxicity can affect pregnancy and its outcome

19. TREATMENT
1.Chelation therapy: This is the fundamental treatment for lead toxicity. Calcium (Ca) EDTA
and succimer are both effective chelating agents, although Ca EDTA is the preferred chelator
for birds
2.Barbiturates or tranquilizers: These may be indicated to control convulsions in animals
with lead poisoning
3.Antioxidant treatment: This may be used in combination with chelation therapy to limit
oxidative damage
4.Thiamine hydrochloride (vitamin B1): Injections of thiamine hydrochloride can reduce the
effects of lead on the animal's nervous system

20. PREVENTION AND CONTROL
.
1.Keep lead-containing materials out of reach of animals: Animals may find material contaminated
with lead in silage, rubbish dumps, around farm buildings, and machinery
2.Properly dispose of lead-containing waste: Proper disposal of lead-containing waste can prevent
animals from being exposed to lead
3.Regularly check for lead-based paint: Regularly checking for lead-based paint and removing it can
prevent pets from ingesting it
4.Take immediate action if lead exposure is suspected: If you suspect your animal has been exposed
to lead, contact your veterinarian immediately
5.Monitor livestock grazing areas: Livestock may be exposed to lead through grazing on
contaminated land. Monitoring grazing areas and removing any sources of lead can prevent lead
toxicity in livestock

21. MERCURY TOXICITY
• Mercury toxicity is a type of metal poisoning that occurs due to
exposure to mercury
• Source of Mercury toxicity
• Exposure to contaminated water
• Exposure to industrial pollution
• Plants grown in mercury-contaminated soil
• Seafood: contaminated fishmeal
• Inhalation of elemental mercury vapors
• Foods stored in pottery with mercury-based paint

22. PATHOGENESIS
• Exposure to Hg vapour induces accumulation of Hg in the testicles, where it exerts
effects on the testicular steroidogenic and spermatogenic functions
• Hg vapour released from amalgam rapidly passes the placenta and is recovered in foetal
blood, pituitary gland and liver as well as in the amniotic fluid which can cause
spontaneous abortions, premature births, congenital disabilities and retardation of fetus
development.
• cellular deformation of the Leydig cells and the seminiferous tubules and testicular
degeneration in all species
• Mercury can alter the shape, movement of sperm and decrease its quantity and quality.
• In men exposed to Hg, a reduction in erection, quality of sexual acts and ejaculation was
found.
• Research indicates that Hg influences the levels and function of estrogen and reduces
fertility in women. Mercury exposure has a relation with polycystic ovary syndrome,
premenstrual syndrome, premature menopause, endometriosis, benign breast disorders

23. SIGNS AND SYMPTOMS
1.Decreased fertility or subfertility: Increased mercury levels have been associated with decreased
fertility or subfertility in both humans and animals
2.Unexplained infertility: Infertile subjects with unexplained infertility have been found to have
higher mercury concentrations in hair and blood
3.Menstrual and hormonal disorders: Mercury levels have been related to a higher incidence of
menstrual and hormonal disorders in women
5.Changes in reproductive behavior: Mercury can accumulate in ovaries and cause changes in
reproductive behavior, infertility, and ovarian failure in females
6.Reduced sperm quality: Mercury exposure can reduce sperm motility, epididymal sperm count,
and normal sperm morphology in animals

24. DIAGNOSIS
1.Clinical signs: Infertility due to mercury toxicity may present with clinical signs such as
decreased fertility or subfertility, menstrual and hormonal disorders, and adverse reproductive
outcomes
2.Laboratory tests: Laboratory tests such as blood and hair mercury levels can help diagnose
mercury toxicity in animals. Infertile subjects with unexplained infertility have been found to
have higher mercury concentrations in hair and blood
3.Exposure history: A history of exposure to mercury can help diagnose infertility due to
mercury toxicity in animals. Exposure to high levels of mercury compounds has been shown to
cause decreased fertility and/or birth defects in animals

25. TREATMENT AND CONTROL
1.No specific treatment available
2.Avoiding high-mercury fish: Avoid consuming high-mercury fish, such as shark, swordfish,
and king mackerel, which can contain high levels of mercury
3.Proper disposal of mercury-containing waste: Proper disposal of mercury-containing
waste can prevent animals from being exposed to mercury
4.Regularly checking for lead-based paint: Regularly checking for lead-based paint and
removing it can prevent pets from ingesting it
5.Monitoring grazing areas: Livestock may be exposed to mercury through grazing on
contaminated land. Monitoring grazing areas and removing any sources of mercury can
prevent mercury toxicity in livestock

26. ARSENIC
Source of Exposure
• Coal
• Pesticides: Dips, sprays, and powders containing arsenic can contaminate vegetation
• Contaminated groundwater: Inorganic arsenic compounds such as arsenite or arsenate can
contaminate groundwater and cause arsenic poisoning in animals
• Herbicides: Inorganic arsenicals are used as herbicides, and cattle can be exposed to arsenic
by eating recently sprayed forage
• Ashes of burned fence posts: Cattle can be exposed to arsenic by licking ashes of burned
fence posts, as arsenic is used as a wood preservative and remains in ashes
• Industrial pollution: Industrial pollution, such as mining and smelting activities, can release
arsenic into the environment and cause arsenic toxicity in animals
• Ingestion: Arsenic poisoning can occur when animals ingest arsenic, which can happen if
they accidentally consume arsenic-containing substances or if they are intentionally
poisoned

27. PATHOGENESIS
• Arsenic binds thiol groups in tissue proteins and impairs the function of the proteins. This
metal affects the mitochondrial enzymes and interrupts the production of energy.
• Oxidative stress.
• High arsenic level may suppress the sensitivity of gonadotroph cells to GnRH as well as
gonadotropin secretion by elevating plasma levels of glucocorticoids. These ultimately
lead to the development of gonad toxicity in animals and cause the reduction in sperm
number, sperm viability and motility.
• Massive degeneration of germ cells and alterations in the level of LH, FSH and
testosterone are also reported.
Signs and Symptoms
• Reduction in testicular weight
• Alterations in sperm number, viability, and motility
• Premature delivery, spontaneous abortion, and stillbirth

28. DIAGNOSIS
• Analysis of arsenic concentration in tissues: Chemical determination of arsenic
concentration in tissues such as the liver or kidney can provide confirmation of arsenic
poisoning in animals
• Analysis of hormone levels: Arsenic exposure can alter the levels of follicle-stimulating
hormone (FSH), luteinizing hormone (LH), and testosterone, which can lead to infertility
in animals
• Histopathological examination: Histopathological examination of reproductive tissues
can reveal the presence of gonad toxicity, which can be caused by arsenic exposure
• Analysis of sperm number, viability, and motility: Arsenic toxicity can cause a reduction in
sperm number, viability, and motility, which can lead to infertility in animals
• Urine and Blood test

29. TREATMENT
1.Antioxidant: Antioxidants such as vitamin E and selenium have been suggested as potential
treatments for arsenic-induced reproductive toxicity in animals
2.Chelation therapy: Chelation therapy, which involves the use of chelating agents to remove heavy
metals from the body, has been suggested as a potential treatment for arsenic toxicity in animals
3.Herbal remedies: Some herbal remedies, such as garlic and ginger, have been suggested as
potential treatments for arsenic-induced reproductive toxicity in animals
4.Nutritional supplements: Nutritional supplements such as zinc and folic acid have been
suggested as potential treatments for arsenic-induced reproductive toxicity in animals

30. PREVENTION AND CONTROL
1.Avoid exposure to arsenic: The best way to prevent arsenic toxicity is to avoid exposure to
arsenic. This can be achieved by avoiding contaminated water sources, food, and soil
2.Regular monitoring of arsenic levels: Regular monitoring of arsenic levels in water, soil, and food
can help to identify potential sources of exposure and prevent arsenic toxicity
3.Use of protective equipment: Protective equipment such as gloves, masks, and goggles can be
used to prevent exposure to arsenic-containing substances
4.Use of chelating agents: Chelating agents succimer can be used to remove arsenic from the
body and prevent toxicity
5.Nutritional supplementation: Nutritional supplementation with antioxidants such as vitamin E
and selenium can help to reduce the oxidative stress caused by arsenic toxicity and prevent
infertility
6.Treatment of infertility: Infertility caused by arsenic toxicity can be treated through various

31. ZINC TOXICITY
SOURCE
1.Ingestion of items: Animals sometimes eat inappropriate items that may have high levels
of zinc, such as pennies, nuts, bolts, zippers, and metal wire cages or toys
2.Chronic overdosing of zinc in ruminants: via dietary zinc or zinc supplements can lead to
cellular degeneration of the liver, pancreas, and kidneys. Pregnant and young animals are
at the greatest risk

32. PATHOGENESIS
• zinc must serve as a master regulator of various processes happening within the sperm to
facilitate the recognition and binding of the male and female sex cells, which enables
fertilization
• Zinc keeps sperm in the non-capacitated state in which they cannot fertilize a female egg.
However, if the zinc is released from the sperm and the capacitation process occurs prematurely
during artificial insemination, the sperm cells will ‘burn out’ and die before reaching the egg, so
the process is very delicate and time-sensitive.

33. SIGNS AND SYMPTOMS
1.Reduction in fertility
2.Negative effects on pregnancy: Maternal zinc deficiency during pregnancy can produce
effects ranging from infertility to embryonic/fetal death to intrauterine growth retardation
3.Decreased egg production: In laying hens, zinc toxicity can cause decreased egg
production
4.Reduced immune function: Zinc excess can lead to reduced immune function, which can
affect fertility in animals

34. DIAGNOSIS
• Clinical Signs
• Blood test
• Liver test
• Histopathology
Treatment
• Decrease Zinc supplementation for male infertility
• Zinc protection against cadmium-induced infertility in female rats

35. CADMIUM
1.Crop contamination: Cadmium can contaminate crops from various soils and chemical
fertilizers, which can lead to cadmium toxicity in animals
2.Ingestion of contaminated herbage or soil: Animals can ingest cadmium by consuming
either contaminated herbage or soil, either following natural or artificial contamination
3.Interference with essential metals: Cadmium can interfere with essential metals such as
calcium, zinc, and iron, leading to toxicity in animal cells
4.Exposure to industrial pollution: Industrial pollution, such as mining and smelting
activities, can release cadmium into the environment and cause cadmium toxicity in
animals
5.Exposure to cigarette smoke: Cigarette smoke is a source of cadmium, and animals
exposed to cigarette smoke can develop cadmium toxicity
SOURCE

36. PATHOGENESIS
Male Infertility : Cadmium damages the cell membrane and the DNA of sperm, limits their motility
and impairs acrosomal reactions
• Cadmium poisoning alkalinizes epididymal fluid, which affects sperm motility
• Lead and cadmium contribute to an increase in the oxidative stress of ruminant semen
• Cadmium impairs fertilization by reducing sperm motility, which limits the penetration of the
oocyte by the sperm
• Cadmium affects the maturation of bovine oocytes and embryo development because it has a
cytotoxic effect
• Acute exposure to cadmium results in testicular necrosis and swelling, hemorrhage, and infertility
due to the disruption of the blood-testicular barrier
• Female Infertility Cadmium is an inducer of reactive oxygen species, which can cause DNA
damage leading to female subfertility/infertility
• Cadmium exposure can alter ovarian progesterone secretion, which can interfere with embryo
transport in the oviduct

37. SIGNS AND SYMPTOMS
• Decreased sperm count
• Deterioration in sperm quality
• Alkalinization of epididymal fluid
• Impaired fertilization
• Testicular necrosis and swelling
• Menstrual cycle disturbances
• Low gestational weight, premature birth, and miscarriages

38. DIAGNOSIS AND TREATMENT
• Diagnosis: Blood test, histological test, Reproductive organ
evaluation, Sperm count, motility, and morphology
• Treatment: No specific treatment
• Prevention and control
• Supplementing with antioxidants
• Reducing environmental exposure
• Avoiding contaminated feed and water

39. ORGANOPHOSPHORUS
TOXICITY(PESTICIDES)
• Source: Insecticides, Military or terrorist action, Medications, Nerve agents etc
• eg DDT, methoxychlor, chlordane, heptachlor, malathion
• MOA: Acetylcholinesterase
• Acetyl choline Acetic acid + choline
• Organophosphorus inhibits Acetylcholine esterase due to which paralysis occurs
• Pathogenesis: Organophosphates could alter the spermatozoon chromatin structure, DNA,
acrosome, and motility and, have toxic effects on the HPG axis, Reduced levels of testosterone
• Oxidative stress
• Organophosphate insecticides induce DNA damage in sperm chromatin and that alters the
spermatogenesis pathway and causes infertility in male animals. Germ cell genetic material is
disrupted
• estrogen, LH, and progesterone production inhibition

41. SIGNS AND SYMPTOMS
• Ovary cycles failure
• Impaired reproduction
• Abnormal urination
Diagnosis: History of exposure, Blood Examinations, cholinesterase analyses
Treatment: Not studied
Prevention and control: Avoid exposure, Use protective equipment, Proper storage and disposal,
Proper storage and disposal, Risk assessment, Medical treatment, Education and training

42. ENDOCRINE DISRUPTING CHEMICALS
• EDCs are chemicals that can mimic or block endogenous hormones in the body leading to a
wide array of health issues, including developmental, reproductive, brain, immune, and other
problems
SOURCE
• Found in everyday products, including plastic bottles and containers, liners of metal food cans,
detergents, flame retardants, food, toys, cosmetics, and pesticides
• Highest-impact EDCs: bisphenol A (BPA), phthalates, and polybrominated diethyl ethers
(PBDEs).
• Industrial food processing, personal care products, and cosmetics, constitute a large source of
phthalates and BPA.
• Dust in the environment
• In animals, in utero exposure to these EDCs has led to abnormal urogenital development,
neurodevelopmental abnormalities, and thyroid disruption.

43. PATHOGENESIS
1. EDCs can mimic or block the action of natural hormones, leading to hormonal
imbalances that can affect fertility.
2.Damage to the female reproductive system: Toxins can cause damage to the ovaries,
uterus, and fallopian tubes. Exposure to toxins can cause inflammation, scarring, and
other damage that can interfere with ovulation, fertilization, and implantation.
3.Damage to the male reproductive system: Exposure to toxins can cause inflammation,
scarring, and other damage that can interfere with sperm production, motility, and
function.
4.Decreased numbers and poor quality of gametes: Exposure to environmental pollutants
and toxins can be directly toxic to gametes (eggs and sperm), resulting in their decreased
numbers and poor quality. Exposure to toxins can cause DNA damage, chromosomal
abnormalities, and other changes that can affect the viability and function of gametes.

44. BISPHENOL A
• BPA is produced and used for plastics, canned food liners, cash register receipts
• It is found in plastic baby bottles, pacifiers, baby toys, computers, cell phones, and reusable
food and drink containers. Exposure is through inhalation, ingestion, and dermal absorption
• BPA has been shown to affect oocyte quality, implantation, embryo development, and
placentation
• BPA toxicity on oocytes occurred in the laboratory of Patricia Hunt, who observed a
spontaneous increase in aneuploid oocytes in mice that coincided with damaged plastic cages
and water bottles. The Hunt team then treated mice with daily oral BPA and induced dose-
dependent increases in oocyte aneuploidy, confirming BPA as the culprit
• In vitro, studies also confirmed that BPA could disrupt meiotic spindle formation
• Higher levels of BPA have associated also with miscarriage

45. BISPHENOL A
• BPA can cross the placenta Some studies have shown BPA to alter gene expression of factors
controlling fetal growth and metabolism
• BPA interferes with epigenetic mechanisms in the placenta
• In men, BPA is associated with decreased semen quality
• Changes in mammary glands and Early puberty seen in animals
• Prostate abnormalities in male animals seen

46. POLYBROMINATED DIETHYL ETHERS
• PBDEs are used in flame retardants on furniture, textiles, carpeting, and some electronics.
• These chemicals are lipophilic, they persist in adipose tissue with a half-life of a few
months to 12 years
• PBDEs can also be detected in fatty fish, lipid-rich oils, and breast milk.
• Another major exposure is through dust brought into the home from shoes and
outerwear
• PBDEs have been detected in the urine of pregnant women
• In an electronics recycling area in China, neonates with the highest PBDE exposure had a
higher incidence of stillbirth, low birth weight, and premature birth
• thyroid abnormalities, a critical hormone for fetal brain development are seen

47. PHTHALATES
• Phthalates are used as intravenous tubing, body lotions, toys, cosmetics, flooring
products, and food processing
• Females with endometriosis had elevated levels of phthalate metabolites
• In-utero exposure to phthalates has been associated with delivery at an earlier
gestational age
• Females undergoing IVF with a higher concentration of phthalates had lower
numbers of oocytes retrieved, lower pregnancy rates, and a higher risk of early
pregnancy loss before 20 weeks gestation
• In men, phthalates have been shown to cause sperm DNA damage
• postnatal exposure to phthalates has been associated with early puberty in girls
• In rats, in utero exposure to phthalates reduced fetal testosterone levels and induced
male reproductive malformations, likely owing to their antiandrogenic actions
• Phthalates can disrupt follicle growth patterns, increase oxidative stress, and cause
follicle death, which could lead to infertility and faster depletion of ovarian reserve

48. PREVENTION AND CONTROL OF EDC
• Treatment of infertility due to EDCs may involve reducing
exposure to these chemicals.
• This can be achieved by avoiding products that contain EDCs,
such as certain plastics, food packaging, and personal care
products
• Eating a healthy diet that is low in processed foods and high in
fruits and vegetables can also help reduce exposure to EDC
• Environmental pollution should be controlled
• Banning the use of plastics

49. THANK
YOU