Review
Cryptorchidism and endocrine disrupting chemicals

https://doi.org/10.1016/j.mce.2011.11.015Get rights and content
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Abstract

Prospective clinical studies have suggested that the rate of congenital cryptorchidism has increased since the 1950s. It has been hypothesized that this may be related to environmental factors. Testicular descent occurs in two phases controlled by Leydig cell-derived hormones insulin-like peptide 3 (INSL3) and testosterone. Disorders in fetal androgen production/action or suppression of Insl3 are mechanisms causing cryptorchidism in rodents. In humans, prenatal exposure to potent estrogen diethylstilbestrol (DES) has been associated with increased risk of cryptorchidism. In addition, epidemiological studies have suggested that exposure to pesticides may also be associated with cryptorchidism. Some case–control studies analyzing environmental chemical levels in maternal breast milk samples have reported associations between cryptorchidism and chemical levels. Furthermore, it has been suggested that exposure levels of some chemicals may be associated with infant reproductive hormone levels.

Highlights

► Some studies suggest that the rate of cryptorchidism has increased since the 1950s. ► Lifestyle factors and environmental endocrine disrupting chemicals EDCs may have a role. ► Chemicals with estrogenic/antiandrogenic effect have caused cryptorchidism in animals. ► Some epidemiological studies suggest linkage between EDC exposure and cryptorchidism. ► More studies are needed to confirm prior results and to evaluate combined exposures.

Abbreviations

AGD
anogenital distance
AGI
anogenital index
AhR
aryl hydrocarbon receptor
AMH
anti-Müllerian hormone
AR
androgen receptor
ARNT
aryl hydrocarbon receptor nuclear translocator
BBP
benzyl butyl phthalate
CGRP
calcitonin gene-related peptide
cis-HE
cis-heptachloroepoxide
CSL
cranial suspensory ligament
DBP
di-n-butyl phthalate
DDT
1,1,1-trichloro-2,2-di(4-chlorophenyl)ethane
DEHP
di-2-ethylhexyl phthalate
DES
diethylstilbestrol
E2B
estradiol benzoate
ED
embryonic day
EDC
endocrine disrupting chemical
ERα
estrogen receptor α
FSH
follicle-stimulating hormone
GREAT
G protein-coupled receptor affecting testicular descent
HCB
heptachlorobenzene
HCE
heptachloroepoxide
HCH
hexachlorocyclohexane
β-HCH
β-hexachlorocyclohexane
Insl3
insulin-like peptide 3
LGR8
leucine-rich repeat-containing G protein-coupled receptor 8
LH
luteinizing hormone
M1
2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid
M2
3′,5′-dichloro-2hydroxy-2-methylbut-3-enanilide
mBP
mono-n-butyl phthalate
mBzP
mono-benzyl phthalate
mCPP
mono-3-carboxypropyl phthalate
mEHHP
mono-2-ethyl-5-hydroxyhexyl phthalate
mEHP
mono-2-ethylhexyl phthalate
mEOHP
mono-2-ethyl-5-oxohexyl phthalate
mEP
mono-ethyl phthalate
miBP
mono-isobutyl phthalate
miNP
mono-isononyl phthalate
mMP
mono-methyl phthalate
PBB
polybrominated biphenyl
PBDE
polybrominated diphenyl ether
PCB
polychlorinated biphenyl
PCDD
polychlorinated dibenzo-p-dioxin
PCDF
polychlorinated dibenzofuran
PE
phthalate ester
p,p′-DDE
1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene
PVC
polyvinyl chloride
RXFP2
relaxin-family peptide receptor 2
T
testosterone
TCDD
2,3,7,8-tetrachlorodibenzo-p-dioxin
TDS
testicular dysgenesis syndrome
SHBG
sex hormone-binding globulin

Keywords

Cryptorchidism
Testis
Endocrine disrupting chemical

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