Endocrine-Disrupting Chemicals and Men's Reproductive Health
Mauri José Piazza1*, Almir Antônio
Urbanetz2
1Department
of Gynecology and Tocogynecology, Federal University of Paraná, Curitiba, Paraná
Brazil
2Department
of Obstetrics and Tocogynecolgy, Federal University of Paraná, Curitiba, Paraná
Brazil
*Corresponding
author: Mauri José Piazza, Department of Gynecology and Tocogynecology,
Federal University of Paraná, Curitiba, Paraná Brazil. Tel: +55-70180710000; Email: mauripiazza@hotmail.com
Received Date: 22 September, 2018; Accepted Date: 08
October, 2018; Published Date: 12 October, 2018
Citation: Piazza MJ, Urbanetz AA (2018) Endocrine-Disrupting Chemicals and Men's Reproductive Health. J Urol Ren Dis 2018: 1126. DOI: 10.29011/2575-7903.001126
1. Abstract
The purpose of this review is to address all agents and mechanisms lihe EDCs(Endocrine Disrupting Chemicals)capable and interfere in the development of the male’s reproductive system which is regulated by hormones and other factors, and the potential consequences caused by these different chemicals.They are known to cause several effects to the male genitalia such as hypospadias, cryptorchidism,testicular cancer as well as interfering with semen quality, therefore determining its correlation with male infertility.
2. Keywords: Endocrine-Disrupting Chemicals; Male Genital Anomalies; Reproductive Health; Testis
3. Introduction
There has been a growing
concern that the incidence of male reproductive disorders is increasingly
higher both in humans and different animal species [1]. Over the past few years, numerous reports show a decrease in the
sperm quality and even the rise of new abnormalities. They have been defined as
Testicular Dysgenesis Syndrome including conditions like hypospadias,
cryptorchidism, not to mention an increased incidence of testicular tumors,
deserving close attention [2-5].
As described previously in Sharpe and Skakkebaek's hypothesis,
Endocrine-disrupting chemicals with oestrogenic effects are considered the
cause for these abnormalities [6]. Possibly, the harmful
effects on Leydig cells of fetal testis contributes to the occurrence of common
abnormalities like hypospadias or cryptorchidism leading to a decreased androgen
production and consequently inducing alterations on the male phenotype. Among
several acting agents of Endocrine-disrupting chemicals and a growing number of scientific
evidence has been collected over the past few years suggesting that human
reproducing capacity has been affected by a wide range of recurrent substances
included in many everyday products. Several indicators are showing an increased
incidence of cardiovascular disorders, obesity, hormone-dependent cancers and
chronic diseases, the early puberty development, pregnancy length disorders and
other reproductive health abnormalities. Among those acting agents have been
defined as Endocrine-Disrupting Chemicals (EDCs).
Endocrine disruptors are chemical
products that may interfere and cause adverse effects on the endocrine system
at any life-stage, given their resemblance to endogenous steroid hormones.Their
actions were determinated like agonist or antagonist against several hormones (estrogens
or androgens). Some EDCs can disturb proteins involved in the transport of
hormones and disrupt the delivery of endogenous hormones to target
cells.Usually the molecular structure consist of a phenol group on the first
ring and one group substitution by chlorine or bromine and mimic steroids
hormones.These situations interfere with synthesis,secretion,transport and
metabolism of diverses hormones and by their similarities induces in
destabilization of hormonal homeostasis.They also alter the number and actions
of different hormone receptors in different cell types and because that alter
the concentration of circulating hormones and blocking their actions. There are
many mechanisms involved and even sometimes not detected.
There are two pathways by which an
EDCs can could disrupt hormone action by a direct action on a hormone-receptor
protein complex or a direct action on a specific protein that control the
hormone-delivery to the right place on the right time. The EDCs act like
hormones and act via biding to receptors in a very low concentrations and
produce synergistic or antagonistic effects. In 2013, Birnbaum showed that between
1947 and 2007,the global production of such chemicals has increased 23.5 times,
whereas in 2012 only,the US produced 9.5 trillion pounds or 2.09 trillion
kilograms of such products including pesticides, plastics,chemical drugs or
even personal hygene products [7]. Deserving
more attention are a very old product DDT and its byproducts such as atrazine
and 2,4-dichlorophenoxyacetic acid found in toys, or others containing plumb
and cadmium,materials used for the production of plastic bottles containing
Bisphenols A, phthalates and several other substances employed in the textile
and apparel industries [7]. Among those acting
agentes there are substances including a Bisphenol A and its byproducts such as
Bisphenol B, Tetrabromobisphenol A and Bisphenol F and S. Some years ago, the
first disruptor detected between those EDC a speciall hormone,was named Diethylstilbestrol
(DES) that propitiated disorders at the genital tract of females ad males
offsprings.
Our proposal is to analyze the
capacity of these agents to affect the men’s Reproductive life and their action
to induce differents diseases in these areas (Table 1).
4.
Methods
We used different sites to detect and search about
different (EDC) Endocrine Disruptors and its correlation with men’s
reproductive life including abnormalities of testis (androgen actions) or male
sexual abnormalities. A large group of papers were analyzed by consultations to
PUBMED, SCIELO and Google Scholar and a great number of papers were analyzed
and selected:
Endocrine Disruptors: PUBMED /SCIELO /
EDC X Testicular Steroidogenesis........ 2001-2016
Bisphenol X Male sexual development.... 2002-2017
Endocrine Disruptors X Sperm quality.... 2009-2016
Endocrine Disruptorsl X Hypospadias.... 2001-2016
Endocrine Disruptors X Cryptorchidism.. 2009-2016
Heavy Metals X Male genital anomalies(Google
acad.)2014-2018..10800 papers
Were revisited a large number of
papers/references and choose the most important articles for analysis by their
good qualities.
5.
Endocrine Chemicals Disruptors (Edc) and Some Historical Particularities
In 1936 the DES (Diethylstilbestrol)
a nonsteroidal was sinthesized revealing a powerful estrogenic
effect.Diethylstilbestrol was defined as the first “endocrine-disrupting
chemical, since anomalies were found in the exposed female offsprings of
pregnant women treated to prevent abortion, the former having later developed
vaginal adenosis, or after that with clear cell adenocarcinoma of the vagina
and/or uterus abnormalities (T Shaped uterus). Bisphenol A
(2,2-bis(4hydroxyphenyl) propane was first synthesized by Dianin in 1891, but
is estrogenic property was only evidenced by Dodds & Lawson in 1936 [3,4]. Later, in 1950 it was observed that
BPA(Bispphenol A)could be polymerized for the manufacturing of plastics given
its lightweight, moldability and impact resistency. The list of Bisphenol
products available in the market has steadly increased, the most common being
Bisphenol S,F,B and AF with different properties.
5.1. DDT(Dichlorodiphenyltricloroethane)-DDE(dichlorodiphenyldichloroethilene)
DDD(dichlorodiphenyldichloroethane)
DDT was synthesized by Paul Muller and first employed in 1936 in Colorado
potato beetles crops. After some years it was a worldwide inseticide used during
the 50’s and 60’s.Was banned in 1972 because its high toxicity,but was
previously employed to combat the “malaria mosquito”. Bysphenil Polychlorinated
was first manufactured in 1927 and 1933 was detected that a direct skin contact
may developed a acne-like condition named
chloracne.Polybrominated-Diphenyl-ether is a flame retardant that may induce severe
neurotoxic effects in humans. Atrazine was invented in 1958 by Geigy
Laboratories,but due its the persistent groundwater contamination was banned in
the European Union.It was prepared from cyanuric chloride and treated with
ethylamine and isopropyl amine.Today near to 800 chemicals are known or are
suspected to be capable and interfering on hormone receptors,hormone synthesis
and their actions.
5.2. Endocrine
Disruptors Are
5.2.1.
Bisphenols: Bisphenol A (BPA)was synthesized in
1891,but evidences showed a low estrogen effect in 1936 with affinity for the
nuclear estrogen receptor. Its effects will depend on the dosage,targeted
tissue and tissular development where it will act. These substances can induce
estrogenic or even antiestrogenic effects, or antiandrogenic and are dependent
on the tissue, according to their impact at receptors [8-10].
Global production of BPA has steadly increased in the latest years given its
mulptiple applications in both plastic and manufacturing industries,food
packaging and toys causing a constant and permanent intoxication of food, water
and the environment. In 1950, it was found Biphosphonates could be polymerized
and, since then, they are used to make polycarbonate plastics. Those plastics
have convenient features such as lightweight, moldability and impact and heat
resistance, not being suceptible to changes over time. Around 20% of those
plastics are used as a component of epoxy resin serving as internal coatings
for containers and plastic bottles. Therefore, it is a liquid and food
contaminant while the human serum analysis has shown variable and abnormal
rates in different studies. Exposure to BPA can occur
by oral ingestion or transdermal/sublingual absorption, suffering a fast
hepatic breakdown [11-13]. Given its lipophilic properties, BPA can easily build-up
in the adipose tissue.
Bisphenols A are rapidly metabolized
to inactive forms with an average life cycle of approximately 4-5 hours in
adults, presenting a relatively low metabolic rate in fetoses and children [10-12]. They can easily accumulate in
adipose tissue having lipophilic properties. Measurements of human serum have
determined varied and controversial toxicity rates.Currently, the United States
Evironmental Protection Agency has established a safe level of 50ug/kg/day and
the European Food Safety Authority has established the tolerable daily intake
should remain below de 4ug/kg/day.
There are a wide range of BPA doses
and is considered a “low dose” below the lowest observable adverse effect in
animals is 50mg/kg/d. Five different types of
Bisphenols are currently being employed in the industry such as Bisphenol B
(BPB), Bisphenol F (BPF), Bisphenol S (BPS), Bisphenol AF (BPAF) and
Tetrabromobisphenol (TBBPA) [14-16] (Figure 1).
BPA..Bisphenol
A...2.2-bis(4-hydroxiphenyl)propane
BPB..Bisphenol B...
2.2-bis(4-hydrophenyl)butane
BPF..Bisphenol F.. 4.4’-(1-phenylethylidene)bisphenol
BPS..Bisphenol S.. 4.4’-sulfonyldiphenol
BPAF.Bisphenol
AF..4.4’-(hexafluoroisopropylidene
TBBPA.Tetrabromobisphenol A
5.2.2.
Phthalates: Phthalates and their esters consist
of a large group of chemical compounds frequently used in the
plastic,coating,cosmetic and toy industries,including the manufacturing of
medical equipment like syringes and blood bags. Phthalates are byproducts of
phthalic acid and are used in the plastics industry having excellent
moldability. Both in the United States and Brazil there are no restrictive
regulations on their use, but the European Community has banned those products
from the market. Among Phthalates, three esters are considered endocrinous
disruptors having estrogenic effects such as DHEP (diethyl-hexyl phthalate),BBP
(benzyl-butyl phthalate) and DBP (dibutyl phthalate).Phthalates can be found
not only in serum and human urine but also in milk samples. Tolerable daily
intake should remain between 3-30ug/kg/dia [13] (Figure
2).
5.2.3.
Atrazine: Atrazine(2-chloro-4-ethylamino-6-isopropylamino-1,3,5-s-triazine)is
largely used in agriculture as herbicide just like chlorotriazine.It has been
used to reduce the growth of leaves and weeds in wheat, soy and sugar cane
cultures due to the inhibition of photosynthesis [11].
Its metabolites remain active for long periods of time and, as pesticides,they
cause water contamination,including water sources for human consumption [14] Atrazine remains in soil for months and the
half-life in soil is 13-261 days (Figure 3).
5.2.4.
Esters of Polychlorinated and
Polybrominated Bisphenols: Polychlorinated
Bisphenols (PCBs) are chemical substances with phenolic ring and different
degrees of chlorination. They were first manufactured in 20’s, being used in
the rubber, resin, adhesives and paint industries [15].
Those chemicals were extensively used around the world contamining schools and
constructions sites.They build up both in the environment and in adipose
tissue, being considered Endocrinous Disruptors with thyroid hormone,
estrogenic and anti-androgenic activity. PCBs were banned from the market in
1979 for its persistent pollutant effects. The polybrominated esters of
Bysphenols were first used as flame retardants and for matresses and covers
manufacturing [15-17]. Amongst all 209
synthesized products which are also polybrominated aromatic, there are the top
5 in toxicity as esters (tetra BDE-47, penta BDE99,-100,-153 and deca BDE-209
or PBDE=Polybrominated diphenyl ethers) [18,19].
5.2.5.
DDT(Dichlorodiphenyltrichloroethane)-DDE(Dichlorodiphenyldichloroethylene)–DDD
(Dichlorodiphenyldichloroethane): These
are chemical compounds once widely used as inseticides with long average life
and strong lipophilic properties.Evidenced as contaminants to the environment, exposure
to these chemicals can lead to several endocrinous diseases although it has
been used to control insects that carry malaria [18].
DDT was banned from the market in 1972 due to its high degree of toxicity. In
addition to DDT, other pesticides deserve to be mentioned such as
hexachlorocyclohexane, chlordane and hexachlorobenzene.These products have been
closely studied not only for persistently building up in nature but also for
being endocrine-disrupting chemicals.However, there are new pesticides being
launched in the market, with shorter average life and similar effects such as
2,4-dichlorophenol,2,5-dichlorophenol and 1-naphthol, present in 50% of
pregnant women in the Salinas Valley,California,USA [20,21].
Other DDT's metabolites include DDE
(Dichlorodiphenyldichloroethylene) and DDD (Dichlorodiphenyldichloroethane
5.2.6.
Diethylstilbestrol (DES= 4.4
dihidroxiestilben): Since
1938 it was a powerful synthetic non-steroidal estrogen,used in the USA, from
1940 to 1975, to prevent abortion and/or its complications. Initially, low
doses of 5mg/day were administered, which were progressively increased to
125mg/day or more, summing up to an average dose of 3650-4000mg. In 1953,
Dieckmann et al proved this treatment to be ineffective [22]. In 1971, Herbst et al assessed young women having noticed a
correlation between the use of DES and the appearence of clear cell vaginal
adenocarcinoma,while in 1976, the same author described other abnormalities in
the genital tract of these young women whose mothers had been treated with DES [23,24]. In 2012 Harris and Waring and Troisi et al in
2014 have noticed a correlation between the increased number of disorders in
the reproductive system of the male and female offsprings whose mothers had
been treated with DES such as cryptorchidism,hypospadias,microphallus,epididymal
cysts and uterine abnormalities like T-shaped uterus and some types of
hormone-dependent cancers [25-27].
5.2.7.
Heavy metals or organometallic: These products such as
Cadmium,Plumb,Mercury,Zinc,Arsenic and Copper have been widely used in various scenarios
leading to a great number of reproductive anomalies by acting as an Endocrine
Disruptor and are called metalhormones. Cadmium is used fin the manufacture of
batteries, metallic pigments and plastics, but exposure to this chemical may
cause harmfull effects to the placental DNA and fetal umbilical cord,building
up in the liver and kidneys.Cadmium can damage testis at Sertoli and Leydig
cells and interfere in semen quality [28]. Plumb
was once extensively used in the manufacture of paints, petrol and toys and its
adverse effects include genomic methylation and a number of different
abnormalities in brain development [29]. Mercury
was once used in several industrial processes and charcoal combustion and human
exposure can occur mainly through contaminated fish ingestion in different
sites like in the Minamata Bay,Japan;Faroe Islands in the North Atlantic; and
the population of Nunavik,Canada. The Mercury accumulation may causes several
damages in the endocrine system and reproductive effects in male and female
humans and animals and on the thyroid and adrenal systems, similar was observed
anteriorly [30] .
6.
Male Sexual Development
Male reproductive system
development begins with the testis differentiation regulated by the 46,XY
chromosome constitution, in the undifferentiated gonads composed of bipotential
and primitive features.Development of the internal genital organs results from
the continuation of the Mesonephric or Wolff ducts due to an androgenic
hormonal activity and the AntiMullerian hormone production in the Sertoli cells
of the fetal testis. Testosterone and dihydrotestosterone regulate the
virilization of the external genital organs due to androgenic influence in the
phallic growth and the anteriorization of the urethra in the penis as well as
the labioscrotal union and fusion,developing the scrotal sac. Timing of
hormonal action is rather accurate and sexual differentiation occurs between
8-15 weeks through gestation.Testicular descent to the scrotal sac depends on
the presence of insulin-like peptide 3 and testis androgens. The production of
testosterone and the development of all other male puberty features will begin
later, at the beginning of puberty, by the action and stimulation of the
central hypothalamic-pituitary.
7. Analyze and Discussion
About Diffrents Edc’s Actions
All these different
stages of male development can be altered by many harmful chemicals as follows.
7.1. Fetal Testis Anomalies
Evidenced that low to high doses of Bisphenol
A may induce fetal testis disorders, including other conditions, from birth to
adult life. Increased infertility rates are associated to the harmful effects
of these endocrine-disrupting chemicals such as lower sperm count, mobility and
DNA damage [27-32].
Those studies are controversial, since LaRocca et al documented daily intakes
of 50-1000ug/Kg/day in pregnant female rats were not harmful to the fetal
testis [27-33].
On the other hand, Tanaka et al showed higher doses would have to be
administered to induce a decrease in the fetal testosterone of those rats [26].
According to well established methods developed by Sharpe and Skakkebaek,in
1993 the term ´Testicular Dysgenesis Syndrome” associates Endocrine-disrupting
chemicals with oestrogenic activities and multiple abnormalities is reduced
sperm count, hypospadias, cryptorchidism and testicular cancer [34]. EDC with estrogenic
effects could cause these disorders and the fetal testis is the major target of
those substances.
7.2. Hypospadia
Is a congenital disorder
in which the urethral opening is found on the ventral part and not on the end
of the penis.In rats was concluded that a testosterone synthesis or action
between 15,5-18,5 days after conception causes masculinization defects with
hypospadias,cryptorchidism and incomplete masculinization and this was caused
by EDC.This period was named as “masculinization programming window” and in
human is between 6,5-14th
gestational week.Topari et al described this condition is more common in a
particular geographic area, however an increased incidence has been documented
in different countries [35]. Case-control studies are often used to identify
hypospadias, using a small number of cases which are not statistically
sufficient to allow accurate conclusions on their causing agents. Rocheleau et
al in a meta-analysis suggested a correlation between the use of pesticides and
an increased risk of developing hypospadias in the offspring of parents
contaminated by these substances. However, since pesticides represent a great
number of substances, it remains unclear if they can be associated to this
anomaly [36].
No significant
association has been made between a great number of different pesticides and an
increased risk of developing hypospadias in further studies by
Morales-Suarez-Varela et al and Rocheleau, et al. [37,38]. Akra et al in 1999 case-control study did not find any
consistent support for an etiologic relationship of increased estrogenic levels
for maternal origin during pregnancy and the occurrence of hypospadias and
cryptorchidism [39] . In their study the
babies with an increased risk for these anomalies were preterm and small for
gestational age. Recent molecular approaches, including gene-targeting in mices
showing that the estrogenic effects of environmental endocrine disruptors and
the effects on external genitalia and depend on individual susceptibility can
cause several grades of hypospadias.Kojima et al described that genes belongs
the Wnt family, homeobox genes and genes for bone morphogenetic proteins and
their actions regulate the external genitalia formation al [40].
7.3. Cryptorchidism
Is a common genital
disorder characterized by an undescended testicle to the scrotal sac affecting
about 1 to 9% of full term baby boys [41]
Acerini and cols evidenced many infants are diagnosed with cryptorchidism in
early childhood, where testicles might not go to the external part of the
scrotal sac. Increased rates of cryptorchidism have been observed, reaching up
to 7% [42]. This might be a family
related condition, resulting from genetic disorders or environmental
determinants. Jensen and cols documented higher incidence rates among
monozygotic twins [43]. Studies in humans
associating the presence of pesticides in patients with cryptorchidism showed
higher concentrations of pesticides like heptachlor epoxide in the adipose
tissue of male boys who underwent orchidopexy surgery-Hoise, et al. [44].
Likewise, high concentrations of chlorinated pesticides were found in the milk
of women breastfeeding boys with cryptorchidism, according to Damgaard and
cols, in 2006 [45]. Nevertheless, the US
CPP Study made no association between cryptorchidism and DDT, DDE, chlordane or
heptachlor epoxide [46].
In turn, another research completed in California by Bhatia et al found
high levels of DDT in the blood of pregnant women whose male baby boys were
diagnosed with cryptorchidism,although no abnormal levels of DDE
(Dichlorodiphenyldichloroethylene) were found [47]. Increased levels of Dioxin and Polychlorinated Biphenyl in flame
retardants were associated to higher incidence of cryptorchidism. As described
previously by Virtanen and cols, in a study including Danish boys with
cryptorchidism,, high levels of dioxin were found in the milk of their mothers,
although no trace of this substance was observed in their placenta [48].
No correlation was made between perfluorinated compounds found in the blood of
the umbilical cord and higher incidences of cryptorchidism according to a
Finish-Danish study by Vesterholm and cols-2014 [49].
Another French
case-control study by Brucker-Davis et al-2008, establishing DDE and
Polychlorinated Biphenyl concentrations, evidenced an increased risk for
cryptorchidism in the exposed group compared to the unexposed group [50]. Many other studies
have been showing the authors’ growing concern regarding this abnormality
genesis and its potential causing agents. In a Study performed in
Denmark-Finland in 2013 by Rantakokko et al was analysed the association of
placenta organotin with congenital cryptorchidism in 280 newborn boys. The
rapid increase in the prevalence of cryptorchidism suggest that environmental
factors-endocrine disruptors may be involved even at very low concentration due
to activation of the retinoid X receptor [51].
7.4. Endocrine Disruptors and Sperm quality
Many contaminating
agents have been associated with their capacity of interfering with sperm
quality including chemotherapy substances,ionizing agents,nicotine and a number
of other chemicals (EDC). All those substances may alter spermatogenesis
affecting spermatogonia,Sertoli cells and causing DNA sperm damage. Such damage
might be temporary or permanent and will depend on each chemical’s intensity of
action. Several studies evaluating the effects of Polychlorinated Bisphenols
(PCB),with variable degrees of chlorination and phenolic ring, observed its
potential damage to sperm quality. Toft and cols, in 2006, and Haugen and cols,
in 2011, documented both positive and negative effects of PCB to sperm quality [52,53]. Two studies by Meeker
and cols, including 167 and 190 male patients recruited in fertility clinics
observed lower levels of inhibin and LH, higher FSH levels and no correlation
with plasma levels of total testosterone as well as free testosterone and
thyroid hormones levels. Also, a reduction on the sperm concentration and great
damage to the DNA sperm has been documented, although the sperms’ shape and
motility remained unaltered [54,55].
In 2010, Mendiola and cols observed increased levels of Bisphenol A associated
to decreased free androgen levels and changes in the free androgen and LH
plasma levels in the semen of 302 infertile man. Other hormones like estradiol,
total testosterone and free testosterone, TSH, T3 and T4 remained unaltered [56]. In 2011, Li and cols
observed low concentrations, decreased sperm count and vitality in the semen of
218 male patients [57]. A
prospective study by Knez and cols, in 2014, evaluated seminal parameters of
129 men undergoing infertility treatment and found decreased sperm count and
lower sperm quality [58]. Lassen and cols, in
2014, evaluated 308 young man of a general population having and average
urinary BPA concentration of 3.3ng/ml finding decreased sperm motility
associated to high levels of total and free testosterone and LH and estradiol [59]. In 2015, Goldstone and
cols in prospective cohort study including 418 man of participating couples
willing to conceive,, assessed different sperm parameters observing a low
percentage of DNA fragmentation while the other seminal parameters remained
unaltered [60]. DNA sperm damage was
also evidenced in the findings of Rozati and cols (2002), Rignell-Hydbom and
cols (2005), Spano and cols(2005) and Stronati and cols (2006) [61-64].
As previously described
by Dallinga and cols, in 2002, and Hauser and cols, in 2003, the incidence of
organochlorinated bisphenols in the plasma revealed opposite reactions,
although no worsening of sperm quality was evidenced in those patients [65,66]. Such
reviews and many other published studies often present conflicting results
showing a correlation between the harmful effects of endocrine-disrupting
chemicals and alterations in the sperm quality,DNA sperm damage also affecting
hormonal activity and significantly interfering with male reproductive health. The
results varied considerably and included positive, inverse or no associations
may times. Heavy metals can interfere on the seminal quality and spermatozoa in
Finnish men study performed by Hovatta and cols (1998).In this group of
patients the serum levels of aluminium,lead and cadmium were increased [29]. Pant e cols (2003)in other
study analysed lead and cadmium concentration in the seminal plasma of men in
fertile and infertile patients. Observed an increase in lead and cadmium levels
and lead semen concentration with sperm motility and sperm concentration in oligoasthenospermic
men [28]. Mocevic, et al. (2013)
in Greenland Inuit group and European men concluded that environmental levels
of mercury were increased and tge semen quality and reproductive hormones can
be disturbed [30].
8. Conclusions
This broad review
reveals the association between exposure to the so-called Endocrine-disrupting
chemicals and a number of different disorders including hypospadias,
cryptorchidism and lower semen quality; having an important role for
understanding male infertility.The evidence on EDCs exposure calls attention to
the idea that EDC’s are responsible to the decline in male reproductive health.
EDCs have been incorporated in a large serie of products like
foods,plastics,clothes,shampoos,soaps,textelis,carpets,toys etc.Rehman et al
described that some countries like France outlawed some products and reduced
the amount of BPA in containers that have contact with foods and the use of
DHEP in toys and others products to childcare [67].In the United States legislation as the Toxic Substances Control
Act and the Safe Drinking Water Act of 1996 gives the Environmental Protection
Agency the power to regulate about substances that may act as an EDCs. WHO(World
Health Organization) by Summary for decision Makers established that a very
large of substances increase susceptibility to a variety of diseases and
disorders and that exposure to EDCs even during the development are capable to
induce several damages [68,69].
However, contradicting
results obtained from other studies require further research comprehending
evaluations that include epidemiological data in order to reach appropriate
conclusions.Better information on how and when EDCs act is needed to reduce
exposure and prevent diseases.It is important that a large number of diseases
have their origin during the development and there are multiples substances
like environmental factors and EDCs that interact with our genetic background
and increase more and more susceptibility to a variety of disorders and
diseases. The WHO recommendations is improve global knowledge of these
chemicals,reduce potential disease risk and cut related cost. Include:- testing known EDCs and more testing methods to identify
possible endocrine disruptors;
- research more scientific evidence is needed to identify
the effects of mixtures of EDCs on humans and wildlife;
- reporting many sources of EDCs that are not known
because insufficient reporting;
- more colaboration between scientists and countries to
detect those substances [70] .
Our conclusion is that a
large group of researches will be necessaries to permit a strong and definitive
idea about diferents EDCs and to analyse their actions in humans and animals
during prenatal and early-life periods and their possible damages to the
genital area.
Figure
1: Comparing the Structural Formulas
of different Bisphenols [16].
Figure
2: Structural formula of Phthalates.
Figure
3: Structural formula of Atrazine.
Figure
4: Structural formulas of
Estradiol(E2) and Diethylstilbestrol and their similarities.
Atrazine/ Alachlor |
Herbicides |
Cadmium chloride/Methiran |
Fungicides |
Carbaryl/Chlordane/DDT, etc. |
Inseticides |
Aldicarb/DBCP |
Nematocides |
Acrylamide |
Water treatment/papear manufacturing |
Ascarel (PCB) |
Adhesives/paints/silo storage coatings |
Benzoanthracene Benzopyrene |
Tar/asphalt/grease/mineral oils |
Bisphenols A, etc. |
Epoxy resin, plastics/can coatings |
Plumbs |
Bateries, paints/pigments |
Polichlorinated Dibenzodioxin |
Pesticide-burn/residues-PVC-diesel |
DBPC (Dibromochloropropane) |
Nematicide |
Carbon Disulfide |
Celophane manufacture/rayon-solvents/wax |
Sthyrene |
Plastic and glasses/rubber manufacturing |
Phenilphenols |
Desinfecting products |
Phthalates |
Plastificants/varnish/cosmetics/inseticides |
HCB (Hexachlorobenzene) |
Organochlorinated processes |
Manganese |
Iron/paint/fertilizers manufacturing |
Mercury |
Agrotoxics/paints/soda industry |
Ethylene Chloride |
Surgical equipment sterilization |
Pentachlorophenol |
Paints/timber conservants/fungicide |
Welding |
Metalsmithing and Weldings/Boilermaking |
Trichlorfon |
Anthelmintics |
Table 1: Several Endocrinous Disrupting-Chemicals and its Actions.