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Vol. 10, No. 1
19
REVIEW
Cryptorchidism and long-term consequences
Maciej Kurpisz1,2, Anna Havryluk3, Andriej Nakonechnyj4, Valentina
Chopyak3, Marzena Kamieniczna2
2
Institute of Human Genetics, Polish Academy of Sciences, Department
of Reproductive Biology and Stem Cells, Poznan, Poland;
3
Danylo Halytsky Lviv National Medical University,
Department of Clinical Immunology and Allergology, Lviv, Ukraine;
4
Danylo Halytsky Lviv National Medical University,
Department of Pediatric Surgery, Lviv, Ukraine
Received: 8 September 2009; accepted: 29 January 2010
SUMMARY
Cryptorchidism has been on the rise for several decades and can be observed
with frequency of 1-2% of males within the first year of age. It may appear
as an isolated disorder or can be a consequence of genetic and endocrine
abnormalities connected with somatic anomalies. Its genetic background
still seems to be unclear although a range of genes can be responsible for
the development of this syndrome. Cryptorchidism can be associated with
serum testosterone level although the often co-existing hypogonadotropic
hypogonadism may also indicate the involvement of pituitary hormones.
Recently, environmental factors have been blamed for cryptorchidism
induction. Autoimmune reactions in conjunction with steroid hormones
regulating immune response can be also partly responsible for cryptorchiCorresponding author: Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska
32, 60-479 Poznan, Poland; e-mail: [email protected]
1
Copyright © 2010 by the Society for Biology of Reproduction
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Cryptorchidism
dism etiology. The appearance of antisperm antibodies can be considered
as a marker or a serious side-effect of uncorrected cryptorchidism. If so, it
could be implied that early surgery (orchidopexy) should be beneficial since
it may prevent antisperm antibodies induction or at least eliminate them in
the post-operative period. Reproductive Biology 2010 10 1: 19-35.
Key words: cryptorchidism, antisperm antibodies, cryptorchidism treatment and diagnosis
INTRODUCTION - TESTICULAR DESCENT
There have been controversies surrounding the precise definition of particular phases of testicular descent. Historically, two critical stages were
proposed, around 12 to 16 weeks of gestation (testis descends the region of
the inguinal ring) with temporary ‘re-ascent’ between 16 and 28 weeks of
gestation due to an increase in the length and thickness of the gubernaculum
[4]. More modern trends indicate at least 3 stages of descent in humans (for
review see: [10]) while Polish authors indicate even 4-5 stages (for review see:
[26]). From all the data available so far, we may agree on principal 3 stages:
1/ nephric displacement of the testis completed with the degeneration of
the mesonephros (weeks of gestation: 7-8); 2/ transabdominal passage that
includes movement of testis from the contact with the metanephros into the
contact with the inguinal ring (completed at 21 weeks); 3/ inguinal passage
or true descent that involves movement of testis from the peritoneal cavity into the lumen of processus vaginalis (28 weeks). There is a variety of
factors including anatomical, genetic, endocrine and environmental which
are associated with this process and which will be mentioned in the other
subchapters of this review.
THE DIAGNOSIS
The term cryptorchidism is derived from the Greek words “kryptos” meaning “hidden” and “orchis” meaning “testis”. Testicular descent into the cool
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(33ºC) environment of the scrotum is necessary to allow normal spermatogenesis. Testicular descent as proposed by Tomiyama et al. [23] is mainly
controlled by Müllerian inhibiting substance (MIS), insulin-3-like hormone
3 (INSL3) and testosterone (T). Out of the monitored population of patients
with cryptorchidism, 10-20% revealed bilateral undescended testes. It is
estimated that at least 6% of these cases are due to an endocrine disorder
[16]. Cryptorchidism is identified in 1-2% of males at 1 year of age [8].
Cryptorchidism (undescended testis, retentio testis or maldescended
testis) is a condition where a testis which should normally be located at
the bottom of the scrotum but instead appears in the abdominal cavity as
a relatively frequent clinical symptom [28]. Cryptorchidism has once been
proposed to be a part of “testicular dysgenesis syndrome” (TDS), which
also includes hypospadiasis, reduced semen quality and testicular cancer
[28]. Clinical examination involves visual description of the scrotum and
palpation when the child is placed in supine, crossed-leg position and, if
possible, in the upright standing position. Asymmetric or hypoplastic scrotum suggests unilateral and bilateral cryptorchidism, respectively [28]. Any
undescended testis after the age of 6 months should be referred for orchidopexy. Cryptorchidism can occur as an isolated disorder in healthy boys,
but it can be also a part of genetic or endocrine disorders, and/or somatic
abnormalities [28].
DEVELOPMENT OF CRYPTORCHIDISM
Genetic factors affecting testicular descent
Regulation of prenatal testicular descent in humans is not fully understood,
but numerous genetic and endocrine factors are involved [tab. 1; 28]. Normal testicular descent is dependent on the intact hypothalamus-pituitarytesticular axis. Malformations of the central nervous system and congenital
hypogonadotropic hypogonadism may be associated with cryptorchidism
[28]. Cryptorchidism with ambiguous genitalia always needs immediate
systematic work-up. Insufficient androgen production or function will induce
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Table 1. Examples of factors that have been proposed to influence testicular
descent*
Factors affecting transabdominal testicular descent
Insulin-like hormone-3 (INSL3)
Leucine-rich repeat-containing G protein-coupled receptor 8 (GREAT or RSFB2)
Estrogens
Factors affecting inguinoscrotal testicular descent
Androgens
Androgen receptor gene
Gonadotropins
Genital femoral nerve (GFN)
Calcitonin gene related peptide (CGRP)
Other factors affecting testicular descent
Hoxa10
Anti-Müllerian hormone (AMN)
AMN receptor gene
*compilation of data reported in Ref. 25
undervirilization of the 46,XY male, due to deficiencies of the 5α-reductase,
steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase, 17α-hydroxylase/17-20 lyase or 17β-hydroxysteroid dehydrogenase
and androgen receptor mutations causing androgen resistance. In the complete forms of Leydig cell hypoplasia or androgen resistance, the external
genitalia are female, with testes located intra-abdominally or in the groin.
The karyotype may vary, but frequently a 45,XO cell line can be found.
Cryptorchidism and testicular dysgenesis or a development of streak gonads may also be seen in chromosome 9p deletion, campomoelic dysplasia
(SOX9 mutation; sry-related HMG-box, high-mobility group) and mutations
in the Wilms tumour (WT-1) or the sex determining region Y (SRY) genes.
In a fenotypically newborn male with bilaterally nonpalpable testes, it is
important to exclude a severely virilized genetic female, like in the case of
congenital adrenal hyperplasia, placental aromatase deficiency or maternal
hyperandrogenism [27, 28].
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The low frequency of mutations in insulin-like hormone 3 and leucinerich repeat-containing G protein-coupled receptors 8 (LGR8) genes in
cryptorchid patients may be linked to the fact that in humans the first phase
of testicular descent is seldom disrupted, i.e. the inguinoscrotal phase is
usually affected. Furthermore, INSL3 may be important also in the second
phase of testicular descent [27].
Hormonal factors affecting testicular descent
Considerable risks of cryptorchidism include: a birth weight less than 2.5 kg,
a size smaller than normal for a given gestational age and prematurity. Placental insufficiency with decreased human chorionic gonadotropin (hCG)
secretion may be the sole underlying factor, as well as low maternal estrogen levels. Intra-uterine growth plays a key role in many male reproductive
disorders [28]. Evidence is emerging that environmental factors may also
play a role in increasing the risk of cryptorchidism in humans. Exposure to
environmental factors, i.e. persistent organochlorines, phthalate monoesters
and smoking, has recently been linked to adverse effects in infant reproductive development. Maternal diabetes, including gestational diabetes, also
appears to be a risk factor for cryptorchidism [28]. In addition, it has been
shown that, although basal plasma T level can be normal in cryptorchid boys,
there is an insufficient increase of T after hCG stimulation when compared
to normal response in approximately 30% of cryptorchid patients [29].
During the last 35 years, histological studies have contributed the most
to our understanding of the etiology of cryptorchidism. Only histological
examination accompanied by and sex hormone level assessment may exemplify hypogonadotropic hypogonadism in the majority of cryptorchid boys
[9]. During pregnancy, hCG may replace the missing function of luteinizing
hormone (LH) and this may explain why not all boys with hypogonadotropic
hypogonadism are born cryptorchid. Pituitary gonadotropins may also have
a role in keeping the testes in scrotal position, since hypogonadotropic hypogonadism may be associated with the ascent of the testes in infancy [27].
The observed associations between hypospadias and genetic abnormalities
of sex chromosome number, androgen receptor function or testosterone path-
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Cryptorchidism
ways provide evidence that the urethral defect occurs as a consequence of failed
induction of the androgen-sensitive urethral plate. Ethnic/racial differences in
maternal serum T during pregnancy may be also responsible for hypospadias.
Other risk factors for hypospadias are: advanced maternal age, paternal risk
factors such as a history of undescended testes and varicocoele, prematurity,
low birth weight syndrome and monozygotic twin’s gestation [19].
Hypospadias and cryptorchidism have been linked with low-birth weight
suggesting that fetal androgen dysfunction plays a role in the etiology of
these conditions, although cryptorchidism can be resolved spontaneously
especially in pre-term infants [1]. Testicular dysgenesis syndrome, especially
hypospadias and cryptorchidism, is programmed by insufficient androgen
function early in fetal life [25].
Environmental factors affecting testicular descent
The relationship between cryptorchidism or hypospadias and environmental factors -xenoestrogens was examined. The results support the environmental working hypothesis for male sexual differentiation in humans.
Since testis descendence is known to be dependent on a balanced steroid
ratio (androgen:estrogen), therefore it is highly sensitive to disruption by
exogenous estrogens [7, 24]. Xenoestrogens would provoke an imbalanced
androgen:estrogen ratio, leading to an inadequate maturation of Sertoli and
Leydig cells. Some authors, however, found no association between cryptorchidism and maternal exposure to xenoestrogens (or pesticides) during
pregnancy [7]. Cryptorchidism can be associated with a specific haplotype
of estrogen receptor alpha gene. It has been proposed that homozygosity for
this haplotype would increase susceptibility to the effects of environmental
endocrine disruptors of estrogenic origin [27].
CONSEQUENCES ON TESTICULAR FUNCTION
According to the TDS concept, one could hypothesize that gonocytes that
reach the testicular basement membrane and begin to differentiate into
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spermatogonia (before Sertoli cells suffered an insult) could be capable of
maturing and differentiating in postnatal life, resulting in semiferous tubules
containing germ cells. On the other hand, intraluminal gonocytes could be
incapable of interacting with the disrupted Sertoli cells, thus preventing
their migration to the basal lamina and resulting in apoptosis thus, leading
to the development of Sertoli cell only syndrome [18].
Cryptorchidism may have the long-term consequences on testicular
function, including disturbed spermatogenesis and risk of testicular cancer,
even after successful treatment [24]. Most previous studies on semen quality
have used the WHO criteria of 20×106 spermatozoa/ml as the lowest normal
sperm concentration. Adult men with persistent bilateral cryptorchidism
have usually azoospermia, whereas after operation 28% of such males had
a normal sperm count. Approximately 49% of men with persistent unilateral
cryptorchidism revealed normal sperm concentration as compared to 71%
after orchidopexy. Few studies have assessed semen quality in relation to
age at performed orchidopexy. Surgery between 10 months and 4 years of
age in bilateral cryptorchidism led to a normal sperm count in 76% of the
cases, compared to 26% when the surgery was performed between 4 and 14
years. In unilateral cryptorchidism this impact of timing was not as obvious:
75% vs. 71% if operated between 10 months to 6 years vs. group of 9-12
years, respectively. It is unknown yet whether current guidelines of earlier
orchidopexy would further improve such outcome [28].
Maturation of germ cells starts with differentiation of gonocytes into
spermatogonia, and is usually completed by the age of 6 months. At the age
of 3 months, dark (Ad) spermatogonia start to appear and steadily increase
in number. This number is reduced in the testes of cryptorchid boys, indicating that there is a failure in the maturation process of the gametogenic cells.
This reduction (in spermatogonia) is more severe than the reduction in the
number of total germ cells. Disproportionate reduction in Ad spermatogonia
correlates directly to future spermiograms and represents the fundamental
abnormality in germ cell development in cryptorchidism [29].
Sperm DNA damage is significantly increased in men with idiopathic
oligozoospermia and in cryptorchid subjects. The finding of increased reactive oxygen species (ROS) levels in infertile subjects may indicate that oxi-
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Cryptorchidism
dative stress is involved in the pathogenesis of sperm DNA damage in these
individuals [21]. High ROS level disrupts the inner and outer mitochondrial
membranes, inducing the release of the cytochrome-c protein and activating
the apoptosis (it augments DNA fragmentation of abnormal spermatozoa;
[2]). Sperm density is variable in both the unilateral and bilateral cryptorchid
males. However important semen morphology, density and motility may
appear, natural fatherhood is the gold standard to assess the fertility of the
cryptorchid male. Thus, bilateral cryptorchidism provoked significant delays
in conceiving as opposed to unilateral cryptorchid patients who impregnated
their partners similarly to normal controls [16].
RECOMMENDED TREATMENT
The optimal treatment regimen for cryptorchidism remains unknown [28].
However, systematic follow-up of patients into adulthood has been observed.
Surgery is currently recommended for congenital cryptorchidism in early
infancy to avoid secondary degeneration of the testis, which is believed to be
caused by the elevated temperature of the nonscrotal gonad(s) [5]. A higher
temperature in experimental cryptorchid testes in rats has been found to
cause high production of ROS as a result of a reduction of superoxide dismutase (SOD) activity in the testicular tissue. The increased ROS level in
the cryptorchid testis is also an important risk factor for the occurrence and
development of testicular tumors [12].
The effects of hormonal therapy on the contralateral (descended testis) have been sporadically studied, the Ad/T [number of adult dark (Ad)
spermatogenic per tubule (T)] was significantly higher in the hormonally
treated boys. It was shown that the differentiation of gonocytes into Ad
spermatogonia is a testosterone-dependent process. If an adequate increase
in plasma T follows hormonal stimulation (hCG), normal germ-cell maturation occurs [29].
Although the treatment is mostly a surgical one, there are some reports
on several cases of testis migration after hormonal treatment with hCG or
gonadotropin releasing hormone (GnRH). A hypothesis that could explain
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the migration of the testicle after using hCG would be the increase of T
level inducing the appearance of androgen receptors on fibroblasts of the
gubernaculums. This would degrade the extracellular matrix and stimulate
the contraction of the muscle fibers in the gubernaculums, thus determining
their shortening [6].
Furthermore, successfully (surgically) treated patients are still at risk
of infertility, but after 6 months of luteinizing hormone-releasing hormone analogue (LHRHa) treatment a long lasting increase in the number
of germ cells in their cryptorchid testis was observed. Recognizing that
the endocrinopathy at mini-puberty is responsible for ensuring infertility
in cryptorchidism, hormonal treatment should be implemented in cryptorchid boys having early successful orchidopexy but still being at risk
of infertility [9].
The undescended testis and the effect of orchidopexy on male fertility
are far from clear-cut. What effect orchidopexy may have on these patients’
fertility in the long term is complicated by numerous other factors. The
issues are: 1/ the age at surgery, 2/ bilateral vs. unilateral cryptorchidism,
3/ the preoperative testicular size, 4/ suture placement and/or testis biopsy,
5/ the accuracy of semen analysis, and 6/ the partner prospective fertility.
What effect does the fixation of the unilateral cryptorchid testis on the
contralateral testis poses another question. A number of statements are
frequently presented as trivial as “higher testis is always worse”, “earlier
surgery is better than later” and “bilateral cryptorchidism is worse than
unilateral” [16]. If hormonal changes are the reason for cryptorchidism,
then the logic implies that hormonal therapy will both: 1/ induce testicular descent, and 2/ increase the number of germ cells as well as improve
fertility [16].
The recommended age for orchidopexy has steadily fallen over the decades with the evolved understanding of spermatogenesis and improvement
in surgical techniques. It is generally assumed that spontaneous descent no
longer occurs after approximately 3 months of age in a term baby, and is
rare beyond 6 months of age (there was a decrease in the germ cells number
in those individuals who underwent surgery after 6 months as compared to
those with surgery at less than 6 months; there was no statistical difference,
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Cryptorchidism
however, in the sperm counts between these two groups 20 years later).
Ludwig and Potempa in 1975 [14] demonstrated 90% of fertility in those
individuals who were operated within the first 2 years of life as opposed to
50% for those who were operated between 9 and 12 years of age. If surgery
was delayed beyond 12 years of age, there was noted a significant decrease
in fertility in this group [16]. There is no evidence that early surgery (for
cryptorchidism) decreases the incidence of testicular cancer [17].
Orchidopexy for bilateral cryptorchidism leads to a higher sperm count
if surgery is performed before 3 years of age as compared to surgery after 4 years of age. Also, the ratio (in sperm count) between the retained
testis and its scrotal counterpart showed a significant increase following
early surgery, while in the late treated group this ratio showed a significant
decrease after surgery. These results strongly suggest that surgery at the
age of 9 months rather than after the age of 3 years is beneficial for proper
testicular development [13].
AUTOIMMUNE BACKGROUND
Studies on testicular autoimmunity are important for a better understanding of human male infertility since it has been suggested that there are
some immunologically-mediated infertile patients among many idiopathic male infertile patients. There are data indicating that unilateral
testicular injury induces a delayed type hypersensitivity (DTH) response
to autologous testicular cells and later indeed induces the contralateral
autoimmune orchitis [20]. Antisperm autoimmunity, namely its cellmediated form, also appears to play a significant role in the impairment
of spermatogenesis [15].
Steroid hormones and male immune system
Steroid sex hormones and GnRH are important factors which modulate the
immune system (tabs. 2 and 3; [22]). Data suggest that GnRH may play an
important role in B-cell immunity. Researchers have been unable to docu-
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Table 2. Summary of experimental data showing the effects of GnRH on the immune system*
Expression of GnRH and GnRH-R
Both are expressed in primary lymhoid organs and peripheral immune
cells including human lymphocytes
Immune system development
Involved in immune system development (no data in humans)
Immune effects
Potent immune-stimulating action; increases the levels of interleukin-2,
interferon-γ, T-helper cells
Impact on autoimmunity
Potential to exacerbate autoimmune disease; effect independent from gonadal
steroids
Sexually dimorphic immune response
Different expression of GnRH and/or G proteins in males and females
*compilation of data reported in Ref. 20
ment an effect of androgens on serum IgG level regardless of the GnRH
presence. Testosterone, 5α-dihydrotestosterone, as well as dehydroepiandrosterone (DHEA) have been equally ineffective in reducing serum IgG level.
On the other hand, T administration clearly suppressed B-cell proliferation
in GnRH-sufficient mice [11].
Much information is available showing that sex steroids such as T and
17β-estradiol (E2) are critically involved in the control of sexual dimorphism
and the immune response. Like other steroids, T and E2 exert their major
long-term effects on cell growth, differentiation, and functions through
intracellular androgen receptors (iAR) and estrogen receptors [(iER)α and
(iER)β], respectively, belonging to the nuclear receptor superfamily. The
iAR and iER are ligand-inducible transcription factors causing activation
or repression of genes. The expression of iAR and iERα suggests direct
responsiveness of B-cells to T and E2. Information is available that both
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Table 3. Summary of experimental data showing the effects of sex steroids on the
immune system*
Expression of steroid receptors
Estrogen (ER) and androgen (AR) receptors are expressed in all immune cell
subsets, except AR in mature B and T-cells
Thymus and bone marrow effects
Testosterone: thymic atrophy, thymocyte apoptosis and B-cell precursor
depletion in bone marrow
Estrogen: same as testosterone, but on different immune subsets
Peripheral T- and B-cells
Testosterone: enhances suppressor T-cells and diminishes B-cell number
Estrogen: enhances helper T-cells and increases autoantibody production
Impact on autoimmunity
Androgens: seem to have suppressor activity
Estrogens: seem to have stimulating activity
Sexually dimorphic immune response
Impact is better expressed during development of immune response; mechanism is unclear
*compilation of data reported in Ref. 20
T and E2 influence the production of immunoglobulin levels. For instance,
T has been shown to inhibit IgM and IgG production by B-cells, while E2
enhances immunoglobulin production. It appears likely that sex hormones
influence B-cells at an early stage of development, also acting as negative
regulators of B cell-lymphopoiesis [3].
Own experience
Our recently obtained but unpublished data from hormonal investigations
indicated that the levels of LH, follicle-stimulating hormone (FSH) and T in
patients with cryptorchidism (age 5-9; n=126 and 10-14 years; n=121) were
not significantly decreased compared to healthy controls. Young patients
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with cryptorchidism (groups of age 0-1; n=7 and 1-4 years; n=81) had also
normal levels of sex hormones.
Data obtained so far showed that in all groups of surgically treated
patients (with cryptorchidism) antisperm antibodies (AsA) were detected.
However, it should be noted that not all AsA families may exert equal
pathognomic values. For example, bound-to-head AsA clearly revealed its
statistically significant potential discriminating group with cryptorchidism
vs. healthy controls while AsA directed to the tail tip did not (tab. 4). It is
interesting that in our young cohorts (groups of 0-1 and 1-4 years of age)
the performed orchidopexy resulted in rapidly decreasing antisperm antibodies levels but in age groups 5-9 and 10-14, the high levels of antisperm
autoantibodies had a long-term impact.
Table 4. Comparison of antisperm antibody (AsA) levels and their isotypes obtained from sera of prepubertal boys with cryptorchidism and healthy controls by
immunobead test*
Cryptorchidism
N=60
AsA
topography
head
neck
principal
piece
tail tip
IgA
IgG
IgM
mean±SD
Healthy individuals
N=23
Positive
individuals
mean±SD
7.93±20.50
0.62± 2.00
3.10± 8.10
n
11
7
11
%
18
12
18
26.71±41.90
22
0.78±1.71
0.13±0.50
0.82±1.70
15
4
15
26 25.74±43.35
Ig class
25
0.13±0.34
7
0.00±0.00
25
0.17±0.39
0.00±0.00
0.00±0.00
0.91± 2.01
Level of
Positive
significance
individuals
(p)
n
%
0
0
0.030
0
0
0.182
4
17
1.000
6
26
0.442
3
0
4
13
0
17
0.373
0.572
0.568
*
analyzed pre-pubertal individuals were classified to Tanner stage I and II; SD: standard deviation;
N: number of cases analyzed in groups under study; n: number of positive cases for AsA;
Statistical differences were obtained by using Mann-Whitney U test
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FINAL REMARKS
The following associations between cryptorchidism and infertility have
been found:
A. Differentiation of gonocytes (that reach the testicular basement
membrane) into spermatogonia is hormonally dependent. In cryptorchid
boys, however, the number of gonocytes is reduced, so it is unclear whether
differentiation failure takes place in the process of germ cells development.
Disproportionate reduction in Ad spermatogonia represents the fundamental abnormality in germ cell development in cryptorchidism (theoretically
in healthy boys adult dark spermatogonia increase in number at the age of
3 months, transformation of gonocytes into spermatogonia takes place at
age of 6 months). Differentiation of gonocytes into dark spermatogonia is
a testosterone-dependent process. The published data show that in patients
with cryptorchidism the levels of T and gonadotropins is low, while increased
plasma T can inhibit IgM and IgG-production by B-cells and is a negative
regulator of B-lymphopoiesis. It can be implied that decreased levels of T, FSH
and LH may explain why production of antisperm autoantibody begins.
B. Apoptosis of germ cells. a/ Sperm DNA damage is significantly increased in males with cryptorchidism (higher temperature in cryptorchid
testis upregulates ROS levels and affects seminal redox balance - such can
be a pathogenesis of sperm DNA damage in these patients). b/ As well as in
the patient with cryptorchidism it was demonstrated that in the hypogonadotropic hypogonadism an unbalanced ratio androgen:estrogen or low hCG
(during fetal life) may be prerequisite to apoptosis of germ cells (this can
be a preliminary step towards the autoimmune reaction!). c/ Autoreactive
B-cells can be rescued from negative selection by antiapoptotic molecules
(Bcl-xL). Testosterone may promote the survival and activation of high
affinity autoreactive B-cells [in systemic lupus erythematosus (SLE) the
higher affinity B-cells may not be only a source of pathogenic autoantibody,
but may also exclude low affinity autoreactive B-cells, thus facilitating the
clearance of apoptotic debris]. It was found that the decreased levels of T,
FSH and LH observed in some cases can explain why the abnormalities in
apoptosis are triggered.
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C. Endocrine mediators (cortisol, estrogen, testosterone etc.) may affect
antigen presenting cells (APC) differentiation and function. Normally, APC
are involved in the antigen degradation and presentation. It was demonstrated that the surgical treatment of cryptorchidism is successful, although
in the absence of the hormonal therapy the low levels of T, FSH and LH in
these patients remain. Normally GnRH shows a potential to exacerbate an
autoimmune disease, while T suppresses the autoantibody production and
diminishes B cell number. It was found in some patients with cryptorchidism that decreased levels of T and gonadotropins can be associated with
the development of autoreactive immune response.
D. Early successful orchidopexy still presents a risk of infertility, although a very little immune autoreactivity in patients from groups of 0-1
and 1-4 years of age was found. It can be hypothesized that the immune
system at this age has little capacity for antibody production.
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