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Biomedical subjects

F Hadziselimović

Publications and source records attributed to F Hadziselimović.

At least 19 recordsLinked to original sources
PubMed2000

Elevated placental estradiol: a possible etiological factor of human cryptorchidism.

PURPOSE: It has been convincingly argued that the increasing incidence of reproductive abnormalities in human males may be associated with increased estrogen exposure during gestation. We documented the expression of estradiol in the syncytiotrophoblast and placenta of males born with cryptorchidism and normal genitalia, respectively. MATERIALS AND METHODS: Tissue from newborn placentas was fixed in glutaraldehyde and embedded in ePON for immunohistological procedures. Cryptorchidism was unilateral in 6 males and bilateral in 1. Semithin histological sections of placental biopsies of these 7 males and 7 randomly selected, normal male placentas were analyzed immunohistochemically with a polyclonal anti-estradiol-17 beta, 6-keto antibody. RESULTS: The weak expression of estradiol in the placentas of normal males was localized predominantly at the basal part of the syncytiotrophoblast in the terminal placental villi. In contrast, all placentas of cryptorchid males had strong expression of estradiol at the basal portion of the syncytiotrophoblast. CONCLUSIONS: The increased expression of estradiol in the syncytiotrophoblast may have an impact on testicular descent.

Cryptorchidism↗
PubMed1997

Treatment with a luteinizing hormone-releasing hormone analogue after successful orchiopexy markedly improves the chance of fertility later in life.

PURPOSE: Infertility has been considered a principal complication associated with cryptorchidism. A particularly high incidence of cryptorchid boys lack the priming effect during the first 3 months of life due to low concentrations of gonadotropins and testosterone (inadequate perinatal stimulation of the testes, which causes infertility). This condition causes impaired transformation of gonocytes into fetal spermatogonia. More pronounced hypogonadotropic hypogonadism results in fewer germ cells. Most importantly, cryptorchid boys with fewer than 0.2 cells per tubular cross section have a high probability of being infertile in adulthood, regardless of whether the condition is unilateral or bilateral and despite apparently successful orchiopexy. MATERIALS AND METHODS: To counteract the paucity of priming hormones, cryptorchid patients with unilateral or bilateral cryptorchidism and a severe paucity of germ cells were treated with a low dose of the luteinizing hormone-releasing hormone analogue buserelin after successful orchiopexy. We analyzed the spermiograms of these patients, who are now young adults, and compared them to those of 23 other men who also had cryptorchidism with a comparable severe paucity of germ cells but who had not received hormonal treatment after successful orchiopexy. RESULTS: Patients who received hormonal therapy after orchiopexy had significantly improved spermiograms compared to those in the control group. Treatment with buserelin increased the number of spermatozoa, improved motility and increased the number of normal forms of spermatozoa. CONCLUSIONS: The luteinizing hormone-releasing hormone analogue buserelin, administered as a nasal spray every other day for 6 months following successful orchiopexy, appears to have a long lasting, positive effect on germ cells. Consequently, the prognosis of fertility has been greatly enhanced in patients treated with buserelin.

Buserelin↗
PubMed1997

The incidence of seminoma and expression of cell adhesion molecule CD44 in cryptorchid boys and infertile men.

PURPOSE: The incidence of seminoma in men with cryptorchid testes is a contentious issue among physicians. Nevertheless, a positive correlation has been shown between the susceptibility for seminoma in patients with the oligo-asthenoteratospermia syndrome and in those with cryptorchid testes. MATERIALS AND METHODS: We histologically examined 5,231 biopsies from 3,867 patients, including 1,121 men with the oligo-asthenoteratospermia syndrome, 218 men with azoospermia and 2,528 boys with cryptorchidism. Testicular tissue embedded in Epon was analyzed by light microscopy, fluorometry, electron microscopy and immunohistochemistry. Cell adhesion molecule CD44 was detected using a monoclonal antibody in all biopsies of patients suspected of having carcinoma in situ. RESULTS: The incidence of seminoma was identical in boys with cryptorchidism and infertile men with the oligo-asthenoteratospermia syndrome but it was significantly higher than in the normal population. All biopsies were analyzed by a single investigator, including 2,528 from 2,403 cryptorchid boys and 2,322 from 1,339 infertile men. Seminoma was found in 4 cryptorchid boys of whom 3 had intra-abdominal testes. The incidence of seminoma in infertile men with the oligo-asthenoteratospermia syndrome was 6/1,121 (4 stage I and 2 stage II). Overall 10 seminomas were noted in 3,867 patients, including 1 in whom seminomas subsequently developed in both testes. Before the onset of puberty primordial germ cells persisted in 7 of the 2,528 cryptorchid patients, although no invasive seminomas were detected. An anti-CD44 monoclonal antibody was found to bind selectively to seminoma cells in the earliest stages of malignant transformation and metastasis, which to our knowledge represents the first reported incidence of CD44 expression associated with seminoma cells. CONCLUSIONS: The incidence of carcinoma in situ in patients with the oligo-asthenoteratospermia syndrome or cryptorchidism was 0.27%. If the occurrence of primordial germ cells is considered, the overall incidence was 0.46% (17 of 3,659 cases). CD44 was expressed in all seminoma cells as well as in all primordial germ cells. Because CD44 adhesion molecules are expressed in the earliest stages of seminoma development, anti-CD44 monoclonal antibody is an important new tool for positively identifying this type of neoplasm in all cases.

Adolescent↗
PubMed1995

Impaired germ cells in secondary cryptorchid testis after herniotomy.

Secondary cryptorchidism was investigated after hernia repair in 15 patients 1 month to 7 years old. Testicular biopsy was obtained during orchiopexy. The number of spermatogonia per tubular cross section was higher in these patients than in boys with primary cryptorchidism, and the differences were significantly greater when the period of cryptorchidism was longer than 5 years. Loss of germ cells in secondary cryptorchidism was lower than in primary cryptorchidism. The spermatogonia per tubular cross section ratios were at the same low level in both groups in adolescence. These differences between primary and secondary cryptorchidism can be due to a lack of testicular exocrine function after a normal priming effect when the testes are in descended position. Collagenization of the peri-tubular connective tissue and the lack of germ cells are the only histological changes that occur in secondary cryptorchid testes when they have remained in cryptorchid position for 2 years, which is in marked contrast to primary cryptorchid testes that did not receive the priming effect in the first months of life. However, fertility is influenced minimally due to the presumably normal functioning of the contralateral testicle. Secondary cryptorchid testes demonstrate significant dysfunction after 5 years in that position. Germ cell loss occurs more slowly in secondary than in primary cryptorchidism. Despite the optimistic prognosis for fertility, we recommend early orchiopexy for secondary cryptorchidism to prevent exocrine insufficiency of the affected testicle.

Child↗
PubMed1991

Early postnatal testicular maldevelopment in cryptorchidism.

It has been previously postulated that many cases of cryptorchidism are manifestations of a forme fruste of hypogonadotropic hypogonadism. In support of this theory the earliest postnatal histological abnormality in cryptorchid testes demonstrated by this morphometric study of semithin microscopic sections of testicular biopsies was hypoplasia of the Leydig cells, which was obvious from the first month of life. The second abnormality, defective transformation of gonocytes into adult dark spermatogonia, was significant from early in life. No reduction in the mean number of germ cells was detected in the first 7 months of life. The abnormal persistence of the untransformed gonocytes resulted in a total germ cell count that was similar to normal controls until the seventh month, when secondary degeneration of untransformed gonocytes led to a decrease in the total germ cell count. These findings are compatible with the hypothesis that the blunted neonatal surge of gonadotropins previously demonstrated in cryptorchid boys triggers a cascade of hormonal and secondary histological abnormalities that may culminate in a reduced fertility potential in adults. Early replacement hormonal therapy deserves further investigation as a rational approach to the treatment of germ cell maldevelopment and reduced fertility potential associated with cryptorchidism.

Biopsy↗
PubMed1991

The morphometric histopathology of undescended testes and testes associated with incarcerated inguinal hernia: a comparative study.

The underlying injury to undescended testes may be hormonal, a transient perinatal form fruste of hypogonadotropic hypogonadism characterized by blunting of the surge in gonadotropins normally seen at age 60 to 90 days. Ischemia is the underlying injury to testes associated with incarcerated inguinal hernias. To determine if the histopathology of these 2 injuries is different histomorphometric analyses were performed on semithin microscopic sections of biopsies of 21 control testes, 17 undescended testes and 13 intrascrotal testes associated with incarcerated inguinal hernias. The infants in all groups were 30 to 120 days old. The results showed that, as in previous studies, undescended testes at this age are characterized by hypoplasia of Leydig cells, normal germ cell counts and defective maturation of gonocytes into adult dark spermatogonia. In contrast, testes associated with incarcerated inguinal hernias were characterized by hyperplasia of Leydig cells, reduced germ cell counts and normal maturation of gonocytes into adult dark spermatogonia. One might conclude that the underlying injury of undescended testes, presumably the blunted surge of gonadotropins, causes a primary hypoplasia and hypofunction of Leydig cells, which in turn causes a secondary defect in transformation of gonocytes into spermatogonia. In contrast, ischemia may primarily cause a tubular epithelial lesion leaving the hypothalamic-pituitary-gonadal axis intact and allowing normal transformation of gonocytes into spermatogonia. Reduced gonadotropins and ischemia appear to produce distinctly different primary and secondary pathophysiological effects on the testes.

Biopsy↗
PubMed1991

Evidence in favor of the mechanical (intrauterine torsion) theory over the endocrinopathy (cryptorchidism) theory in the pathogenesis of testicular agenesis.

There are 2 competing theories regarding the pathogenesis of testicular agenesis--the endocrinopathy/cryptorchidism and the mechanical/intrauterine torsion theories. We compare the number of Leydig cells, total number of germ cells and the transformation of adult dark spermatogonia into primary spermatocytes in semithin sections of testicular biopsies from 59 contralateral descended testes of patients with testicular agenesis with those in the contralateral descended testes from 250 patients with unilateral cryptorchidism. The contralateral descended testes from boys with testicular agenesis demonstrated higher numbers of Leydig cells, higher numbers of total germ cells and a higher rate of transformation of adult dark spermatogonia into primary spermatocytes than did the contralateral descended testes from the patients with unilateral cryptorchidism. These findings favor the mechanical/intrauterine torsion theory over the endocrinopathy/cryptorchidism theory in the pathogenesis of testicular agenesis.

Biopsy↗
PubMed1987

Long-term effect of luteinizing hormone-releasing hormone analogue (buserelin) on cryptorchid testes.

We studied 48 prepubertal boys with cryptorchidism between 1 year 3 months and 11 years old who were treated with buserelin every other day for 6 months. Urinary luteinizing and follicle-stimulating hormones, and testosterone remained unchanged during the entire treatment period. In boys older than 7 years a slight but significant increase in testosterone was noted in the first morning voided urine at the end of treatment. Testicular biopsies were obtained at orchiopexy in all patients in whom testicular descent was not complete (83 per cent). A significant increase in the number of germ cells was observed in patients with unilateral and those with bilateral cryptorchidism, indicating that 6 months of buserelin therapy improved the fertility status even when testes were in an undescended position during treatment.

Administration, Intranasal↗
PubMed1987

Effect of treatment with chronic gonadotropin releasing hormone agonist on human testis.

We removed and examined 24 testes from 12 patients with metastatic carcinoma (stages C2 and D2) of the prostate who had been treated previously with either the gonadotropin releasing hormone analogue buserelin alone or combined buserelin and flutamide for a mean of 13.8 months. The histological changes noted included severe generalized atrophy of the seminiferous tubules, prominent degeneration of the Sertoli cells, with ultimate total tubular hyalinization, partial Sertoli-cell-only syndrome in 50 per cent of the testes (number of germ cells less than or equal to 0.95 per tubule), and pronounced collagenization and fibrosis of the interstitium (50 per cent) with total atrophy of the Leydig cells in 92 per cent of the testes. These results show that the effect of prolonged high doses of buserelin in the majority of patients caused irreversible damage, particularly to spermatogenesis and the Sertoli cells, and thus to the intratesticular ultra-short loop. Therefore, when it is applied continuously in a high dose daily for a long period this drug does not appear to be suitable as a male contraceptive.

Aged↗
PubMed1986

Testicular histology in children with unilateral testicular torsion.

Testicular biopsies from 38 boys at the time of unilateral testicular torsion were studied retrospectively. Of the patients 30 were adolescent and 8 were prepubertal. In 18 boys biopsy of the torsed testis only was performed, while in another 18 bilateral testis biopsy was obtained. The remaining 2 patients had biopsy of the contralateral testis only because the torsed testis was infarcted completely. After allowances were made for the acute testicular changes associated with the torsion itself, significant pre-existing testicular abnormalities could be identified in 20 of the 38 patients (53 per cent), including the Sertoli-cell-only syndrome (7), partial Sertoli-cell-only syndrome (4), defective spermatogenesis (8) and mucous plugs caused by cystic fibrosis inducing tubular changes (1). In 70 per cent of the biopsies from prepubertal boys the number of spermatogonia per tubule was diminished. In adolescent boys the mean number of late spermatids also was diminished severely in the contralateral and torsed testes. Pronounced atrophy of Leydig cells was found in all but 1 testis examined. The presence or absence of a morphological blood-testis barrier did not appear to be related to pathological changes in the contralateral testis. These observations suggest that infertility in patients with unilateral testicular torsion may be a consequence of a pre-existing testicular pathological condition.

Adolescent↗
PubMed1986

The significance of postnatal gonadotropin surge for testicular development in normal and cryptorchid testes.

Testicular biopsies from 29 infants with cryptorchidism between birth (gestational age as early as 36 weeks) and 9 months of age were compared to 34 biopsies from the testes of boys at postmortem examination, or during operation for a hydrocele or hernia. The total number of germ cells was similar in both groups but normal testes showed a transformation of gonocytes into spermatogonia to an extent that was not seen in the cryptorchid testes. Cryptorchid testes also showed markedly reduced numbers of Leydig cells compared to normal. These postnatal changes occurred in the normal testes at the same time that the increase is seen in luteinizing and follicle-stimulating hormones during the first few months of life and they are believed to be a consequence of this hormonal activity. It is postulated that the postnatal surge of gonadotropins may be responsible for priming the testes for subsequent development and fertility.

Biopsy↗
PubMed1984

The value of testicular biopsy in cryptorchidism.

This prospective study conducted on 24 children, who have now reached adulthood, was undertaken to determine the value of testicular biopsies in cryptorchidism relative to fertility prognosis. A significant correlation between the number of germ cells in the biopsy and sperm count was found to exist (p less than 5%). Thus, the testicular biopsy performed during orchiopexy was found to have a prognostic value. The hormonal findings (LH, FSH) suggest that in cryptorchid adults impaired Leydig cell function exists only when serious tubular damage is present. Because of its prognostic value with respect to fertility and the probability of discovering carcinoma in situ cells, it is strongly recommended that a testicular biopsy is performed in cryptorchid boys.

Adolescent↗
PubMed1984

[4 years' experience with combined hormonal treatment of cryptorchism].

86 patients aged 9 months to 15 years (means = 4.8) having 102 cryptorchid testes were treated with either LHRH nasal spray or with a combination of LHRH and HCG. The immediate success rate after the termination of treatment was 74%. The follow-up showed that 65% of the testes were still descended after the critical period had elapsed. An open processus vaginalis was found in 74% (20/27) while pathological changes of the epididymis (64%) (7/11) and testis "reflexus" (48%) (13/27) were frequently encountered in unsuccessfully treated patients. Furthermore, the above grouping of patients displayed typical histological changes associated with cryptorchidism, namely an impaired number of germ cells (0.14 S/T median values) and atrophy of the Leydig cells. In almost all of the patients classified as treated unsuccessfully, there was a definite improvement in the position of the gonad, thus facilitating subsequent surgery.

Adolescent↗
PubMed1982

Pathogenesis and treatment of undescended testes.

Impaired intrauterine gonadotropin secretion was the cause of cryptorchidism in 78% of cryptorchid boys studied. On the one hand, this impairment implied the underdevelopment of the epididymis and thus the cryptorchid state of the gonad. On the other hand, the histological alterations of the testis, due to impaired gonadotropin secretion were Leydig cell atrophy and an impairment in the number of the germ cells. The secondary damage, due to the unfavorable position, started during the second year of life. To avoid this damage, early treatment is highly recommended. Hormonal treatment with GnRH is the treatment of first choice. This treatment was successful in 60% of cryptorchid boys. An additional treatment of nonresponders with low doses of hCG increased the overall success rate to 80%. Six months after treatment, 14.5% of those successfully treated suffered a relapse.

Animals↗