SUGGESTION OF ABNORMAL TESTICULAR STEROIDOGENESIS IN SOME OLIGOSPERMIC MEN

1978 ◽  
Vol 87 (2) ◽  
pp. 400-412 ◽  
Author(s):  
Luis J. Rodriguez-Rigau ◽  
David B. Weiss ◽  
Keith D. Smith ◽  
Emil Steinberger
Keyword(s):  
Normal Control ◽  
Normal Volunteer ◽  
Testicular Biopsy ◽  
Testicular Tissue ◽  
Biosynthetic Activity ◽  
Testicular Steroidogenesis ◽  
17 Hydroxyprogesterone ◽  
Tissue Specimens ◽  
Steroid Dehydrogenase

ABSTRACT Androgen biosynthesis in the testis may be analyzed in some detail by means of techniques of in vitro incubation of small testicular biopsy specimens with suitable radiolabelled precursors. Sixty-six tissue specimens from 33 patients who underwent bilateral testicular biopsies because of infertility were incubated in vitro with [3H]pregnenolone in order to investigate the possibility of abnormalities in their steroid biosynthetic activity. As a normal control, testicular tissue obtained by testicular biopsy from a young normal volunteer was used. The distribution of metabolites in the incubates of testes from 8 infertile men differed greatly from the remaining 25 patients and the normal control. The major steroids formed from pregnenolone by the testes of those 8 men were 17-hydroxypregnenolone, dehydroepiandrosterone, 20α-dihydropregnenolone and 20α-dihydro-17-hydroxypregnenolone. Very small amounts of Δ4-3 oxo products (progesterone, 17-hydroxyprogesterone, androstenedione and testosterone) were formed suggesting a deficiency of 3β-hydroxy-steroid-dehydrogenase activity in the testes of these 8 men, possibly related to the derangement of their spermatogenic function.

P–056 To graft or not to graft? Intratesticular grafting of testicular tissue from Klinefelter boys to the mouse testis as possible novel in vivo model

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M Willems ◽  
P Sesenhausen ◽  
I Gies ◽  
V Vloeberghs ◽  
J D Schepper ◽  
...  
Keyword(s):  
Klinefelter Syndrome ◽  
Testicular Biopsy ◽  
Testicular Tissue ◽  
Mouse Testis ◽  
In Vivo Model ◽  
Seminiferous Tubules ◽  
Positive Effects ◽  
Fibrotic Process

Abstract Study question Can intratesticular transplanted testis tissue from Klinefelter boys to the mouse testis be used to study the mechanisms behind testicular fibrosis? Summary answer Grafting of testicular tissue from Klinefelter boys to the mouse testis is not a valuable new in vivo model to study Klinefelter-related testicular fibrosis. What is known already Klinefelter syndrome (KS; 47, XXY) affects 1–2 in 1000 males. Most KS men suffer from azoospermia due to a loss of spermatogonial stem cells. Additionally, testicular fibrosis is detected from puberty onwards. However, mechanisms responsible for fibrosis and germ cell loss remain unknown. An optimal in vivo model to study the KS testicular fibrotic process is not available. This study aimed to evaluate a possible in vivo model to study KS-related testicular fibrosis. In addition, the effect of the mast cell blocker ketotifen, which showed positive effects on fertility in infertile non-KS patients, was evaluated in this graft model. Study design, size, duration First, the survival time of the KS graft was established, since it was the first time KS tissue was transplanted to the mouse testis. Testes were collected after two, four, six and eight weeks after which histological and immunohistochemical evaluations were performed. Next, the effect of daily ketotifen injections on the fibrotic appearance of intratesticular grafted testicular tissue from KS and controls was evaluated. Participants/materials, setting, methods Testicular biopsy samples from pre- and peripubertal KS (n = 22) and age-matched control samples (n = 22) were transplanted to the testes of six weeks old Swiss Nu/Nu mice (n = 22). Prior to grafting, testicular tissue pieces were cultured in vascular endothelial growth factor (VEGF) for five days. Next, tissues were transplanted to the mouse testes. Testicular transplants were analysed by immunohistochemistry. In the second experiment, mice were given daily subcutaneous injections of ketotifen or saline. Main results and the role of chance Four weeks after transplantation, all KS grafts could still be retrieved. At a later timepoint, degeneration of the tissue could be detected. In the grafts, recovered four weeks after transplantation, about 30% of the tubules in peripubertal grafts showed a good integrity, while in the prepubertal tissue, 83% of the tubules were intact. A fibrotic score was assigned to each graft. No significant changes in fibrotic score was observed between testicular biopsies before or after transplantation. However, an increased (p < 0.01) fibrotic score was observed after in-vitro treatment with VEGF both in control and KS tissue. Based on recovery and tubule integrity grafts were recovered after four weeks in the second experiment. Treatment with ketotifen did not result in significant histological differences compared to non-treated grafts (KS and control tissue). The survival potential of grafts from KS testicular biopsies of pre- and peripubertal boys was patient- and age-dependent. After four weeks, most KS tissue starts to degenerate. In prepubertal tissue, seminiferous tubules were mostly intact, while tissue from adolescent boys was impaired. Interestingly, no loss of germ cells was observed after transplantation of the testicular tissue. Limitations, reasons for caution The availability of tissue from young KS patients is very scarce, leading to a low number of included patients (n = 8). Testicular tissue pieces from the same patient were included to evaluate the differences before and after transplantation. However, histological variability between testicular tissue biopsy pieces is well-known in KS patients. Wider implications of the findings Since testicular tissue from KS boys, transplanted to the mouse testes, already starts to degenerate after four weeks and the integrity is not optimal, we conclude that this is not a valuable model for future studies. In vitro models to study the KS-testicular fibrosis should be investigated. Trial registration number NA

BIOSYNTHESIS OF TESTOSTERONE AND OESTROGENS IN VITRO BY THE TESTICULAR TISSUE FROM PATIENTS WITH KLINEFELTER'S SYNDROME

1971 ◽  
Vol 66 (4) ◽  
pp. 737-744 ◽  
Author(s):  
Dinesh C. Sharma ◽  
J. Lester Gabrilove
Keyword(s):  
Normal Control ◽  
Testicular Tissue ◽  
Klinefelter’S Syndrome ◽  
Klinefelter's Syndrome ◽  
Positive Form ◽  
Control Subjects ◽  
End Products ◽  
Testis Tissue

ABSTRACT Testis tissue from patients with the chromatin positive form of Klinefelter's syndrome was incubated with 17α-hydroxyprogesterone and testosterone. The ratio of oestrogen to testosterone in the end products of the incubation utilizing 17α-hydroxyprogesterone as substrate was 5 to 10 times the ratio obtained in similar investigations employing testis from normal control subjects. An increased conversion into oestrogen of testosterone utilized as substrate was also observed in the in vitro studies of testis obtained from the patients with Klinefelter's syndrome. These data lend support to the thesis that in the chromatin positive form of Klinefelter's syndrome there is an increased conversion of testosterone into oestrogen in the testis.

STEROID BIOSYNTHESIS IN VITRO BY GONADAL TISSUES IN TRUE HERMAPHRODITISM

1972 ◽  
Vol 69 (1) ◽  
pp. 119-126 ◽  
Author(s):  
Shutaro Mizutani ◽  
Takao Sonoda ◽  
Jun-ichi Furuyama ◽  
Michio Takemura ◽  
Keishi Matsumoto
Keyword(s):  
Ovarian Tissue ◽  
Testicular Tissue ◽  
Steroid Biosynthesis ◽  
True Hermaphroditism ◽  
Metabolic Conversion ◽  
17 Hydroxyprogesterone ◽  
Normal Adults

ABSTRACT Gonadal tissues from a patient with true hermaphroditism were homogenized and incubated both separately and in combination with [4-14C] progesterone and [7α-3H] pregnenolone as substrates. The following metabolites were isolated and identified in the testicular portion from progesterone: 17-hydroxyprogesterone, 16α-hydroxyprogesterone, 20α-hydroxy-pregn-4-en-3-one, androst-4-ene-3,17-dione and testosterone. In addition, 17-hydroxypregnenolone, dehydroepiandrosterone and androst-5-ene-3β,17β-diol were isolated from pregnenolone as substrate. Incubation of the ovarian portion with progesterone gave 17-hydroxyprogesterone and 16α-hydroxyprogesterone. In addition, 17-hydroxypregnenolone and small amounts of dehydroepiandrosterone were isolated from pregnenolone. In these respects, the testicular portion resembled testicular tissue and the ovarian portion resembled the ovarian tissue of normal adults. Analysis of the products obtained suggest that this testicular tissue preferentially uses the Δ5-pregnenolone pathway rather than the Δ4-pro-gesterone pathway in its metabolic conversion to testosterone.

Prognostic factors for the success of obtaining spermatozoa with a biopsy of testicular tissue in men with severe forms of pathozoospermia

2020 ◽  
pp. 96-97
Author(s):  
Т.А. Яманди ◽  
Н.Ю. Сафина ◽  
В.Б. Черных ◽  
Л.В. Акуленко
Keyword(s):  
Prognostic Factors ◽  
In Vitro Fertilization ◽  
Y Chromosome ◽  
Testicular Biopsy ◽  
Testicular Tissue ◽  
Inhibin B ◽  
Severe Oligozoospermia ◽  
Vitro Fertilization ◽  
Azf Region

Приводятся данные обследования мужчин с азооспермией и олигозооспермией тяжелой степени, имеющих и не имеющих микроделеции длинного плеча Y-хромосомы, а также результаты биопсии тестикулярной ткани. Отсутствие делеций региона AZF, отсутствие гипоплазии яичек, а также нормальные показатели ФСГ, ЛГ и ингибина В являются прогностически благоприятными критериями в отношении успешности получения сперматозоидов при биопсии ткани яичка для проведения экстракорпорального оплодотворения (ЭКО). The article presents the results of a survey of men with azoospermia and severe oligozoospermia, with and without microdeletion of the long arm of the Y chromosome, as well as the results of a testicular biopsy. The absence of deletions of the AZF region, the absence of testicular hypoplasia, as well as normal levels of FSH, LH and inhibin B are prognostically favorable criteria for the success of obtaining spermatozoa with a biopsy of testicular tissue for in vitro fertilization (IVF).

The effect of prenatal treatment with busulfan on in vitro androgen production by testes from rats of various ages

1985 ◽  
Vol 63 (9) ◽  
pp. 1155-1158 ◽  
Author(s):  
Gwenderlyn F. Jansz ◽  
David K. Pomerantz
Keyword(s):  
Leydig Cells ◽  
Testicular Tissue ◽  
Developmental Changes ◽  
Seminiferous Tubules ◽  
Apparent Paradox ◽  
Old Rats ◽  
Effect Of Treatment ◽  
Hydroxy Steroid ◽  
Steroid Dehydrogenase

Treatment of rats with busulfan in utero severely depletes the germ cell population of the seminiferous tubules. These studies have examined the in vitro capacity of testicular tissue and Leydig cells from such testes to secrete androgens. Leydig cells were identified by staining for 3β-hydroxy steroid dehydrogenase. Rats were studied at several ages to identify any developmental changes in the androgen-secreting capacity of control and treated gonads. At 30 days of age, no effect of treatment on serum androgen was found. At 60 and 90 days of age, treatment caused decreased androgen and increased LH content of the serum. At 12, 30, 60, and 90 days of age, the amount of androgen secreted per milligram of testicular tissue in response to LH was higher in busulfan-treated rats. Leydig cells from 60- and 90-day-old rats which had received busulfan were also hyperresponsive to LH. It was concluded that Leydig cells from testes essentially devoid of germ cells were hyperresponsive to LH. Serum androgen levels were decreased yet androgen production per Leydig cell was increased. A possible explanation of this apparent paradox is that busulfan treatment resulted in decreased numbers of Leydig cells in the gonads.

scholarly journals Involvement of inducible nitric oxide synthase in stress-impaired testicular steroidogenesis

1999 ◽  
Vol 163 (3) ◽  
pp. 409-416 ◽  
Author(s):  
TS Kostic ◽  
SA Andric ◽  
D Maric ◽  
SS Stojilkovic ◽  
R Kovacevic
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathway ◽  
Immobilization Stress ◽  
Testicular Tissue ◽  
Nitrite Production ◽  
Testicular Steroidogenesis ◽  
No Signaling ◽  
Serum Androgens

The immobilization stress induces an acute inhibition of testicular steroidogenesis that is mediated by the nitric oxide (NO) signaling pathway. Here we compared the effects of 2-h immobilization stress on in vivo and in vitro rat steroidogenesis at two time points, 0 h and 6 h after the end of the stress session. As expected, serum androgens and human chorionic gonadotropin (hCG)-stimulated progesterone and testosterone production by testicular tissue were inhibited at 0 h, and also at the 6-h time point. Both the acute and sustained inhibitions of in vitro steroidogenesis were accompanied by a significant increase in nitrite, a stable oxidation product of NO. To clarify which subtype of NO synthase (NOS) (constitutive (cNOS) or inducible (iNOS)) participates in down-regulation of testicular steroidogenesis, aminoguanidine hydrochloride (AG), a selective iNOS inhibitor, was employed. Intratesticular injection of AG prevented the sustained, but not the acute, stress-induced decrease in serum testosterone. When added in vitro, it also prevented the sustained decrease in steroid production and increase in nitrite production by testicular tissue, both in a dose-dependent manner and with EC microM. Furthermore, AG added in vivo and in vitro effectively blocked the sustained decrease in 3beta-hydroxysteroid dehydrogenase (3betaHSD) and 17alpha-hydroxylase/C17-20 lyase (P450c17) activities. In all concentrations employed, AG did not affect serum androgens and in vitro steroid and nitrite production in unstressed animals. These results indicate that the NO signaling pathway participates in acute and sustained stress-induced down-regulation of testicular steroidogenesis, presumably through its direct action on 3betaHSD and P450c17. The acute NO production is controlled by cNOS and the sustained production of this messenger is controlled by iNOS.

scholarly journals Cellular Therapy via Spermatogonial Stem Cells for Treating Impaired Spermatogenesis, Non-Obstructive Azoospermia

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1779
Author(s):  
Nesma E. Abdelaal ◽  
Bereket Molla Tanga ◽  
Mai Abdelgawad ◽  
Sahar Allam ◽  
Mostafa Fathi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Male Infertility ◽  
Cellular Therapy ◽  
Antihypertensive Drugs ◽  
Testicular Biopsy ◽  
Testicular Tissue ◽  
Spermatogonial Stem Cells ◽  
Obstructive Azoospermia ◽  
Promising Alternative ◽  
Major Health Problem

Male infertility is a major health problem affecting about 8–12% of couples worldwide. Spermatogenesis starts in the early fetus and completes after puberty, passing through different stages. Male infertility can result from primary or congenital, acquired, or idiopathic causes. The absence of sperm in semen, or azoospermia, results from non-obstructive causes (pretesticular and testicular), and post-testicular obstructive causes. Several medications such as antihypertensive drugs, antidepressants, chemotherapy, and radiotherapy could lead to impaired spermatogenesis and lead to a non-obstructive azoospermia. Spermatogonial stem cells (SSCs) are the basis for spermatogenesis and fertility in men. SSCs are characterized by their capacity to maintain the self-renewal process and differentiation into spermatozoa throughout the male reproductive life and transmit genetic information to the next generation. SSCs originate from gonocytes in the postnatal testis, which originate from long-lived primordial germ cells during embryonic development. The treatment of infertility in males has a poor prognosis. However, SSCs are viewed as a promising alternative for the regeneration of the impaired or damaged spermatogenesis. SSC transplantation is a promising technique for male infertility treatment and restoration of spermatogenesis in the case of degenerative diseases such as cancer, radiotherapy, and chemotherapy. The process involves isolation of SSCs and cryopreservation from a testicular biopsy before starting cancer treatment, followed by intra-testicular stem cell transplantation. In general, treatment for male infertility, even with SSC transplantation, still has several obstacles. The efficiency of cryopreservation, exclusion of malignant cells contamination in cancer patients, and socio-cultural attitudes remain major challenges to the wider application of SSCs as alternatives. Furthermore, there are limitations in experience and knowledge regarding cryopreservation of SSCs. However, the level of infrastructure or availability of regulatory approval to process and preserve testicular tissue makes them tangible and accurate therapy options for male infertility caused by non-obstructive azoospermia, though in their infancy, at least to date.

scholarly journals The Expression Levels and Cellular Localization of Pigment Epithelium Derived Factor (PEDF) in Mouse Testis: Its Possible Involvement in the Differentiation of Spermatogonial Cells

2021 ◽  
Vol 22 (3) ◽  
pp. 1147
Author(s):  
Noy Bagdadi ◽  
Alaa Sawaied ◽  
Ali AbuMadighem ◽  
Eitan Lunenfeld ◽  
Mahmoud Huleihel
Keyword(s):  
Cellular Localization ◽  
Pigment Epithelium ◽  
Testicular Tissue ◽  
Seminiferous Tubules ◽  
Target Cells ◽  
Isolated Cells ◽  
Expression Levels ◽  
Cellular Origin ◽  
Pigment Epithelium Derived Factor

Pigment epithelium derived factor (PEDF) is a multifunctional secretory soluble glycoprotein that belongs to the serine protease inhibitor (serpin) family. It was reported to have neurotrophic, anti-angiogenic and anti-tumorigenic activity. Recently, PEDF was found in testicular peritubular cells and it was assumed to be involved in the avascular nature of seminiferous tubules. The aim of this study was to determine the cellular origin, expression levels and target cells of PEDF in testicular tissue of immature and adult mice under physiological conditions, and to explore its possible role in the process of spermatogenesis in vitro. Using immunofluorescence staining, we showed that PEDF was localized in spermatogenic cells at different stages of development as well as in the somatic cells of the testis. Its protein levels in testicular homogenates and Sertoli cells supernatant showed a significant decrease with age. PEDF receptor (PEDF-R) was localized within the seminiferous tubule cells and in the interstitial cells compartment. Its RNA expression levels showed an increase with age until 8 weeks followed by a decrease. RNA levels of PEDF-R showed the opposite trend of the protein. Addition of PEDF to cultures of isolated cells from the seminiferous tubules did not changed their proliferation rate, however, a significant increase was observed in number of meiotic/post meiotic cells at 1000 ng/mL of PEDF; indicating an in vitro differentiation effect. This study may suggest a role for PEDF in the process of spermatogenesis.

Plasma Inhibitory Activity against Tumour Necrosis Factor in Fulminant Hepatic Failure

1996 ◽  
Vol 90 (1) ◽  
pp. 77-80 ◽  
Author(s):  
Helen M. Keane ◽  
Nick Sheron ◽  
John Goka ◽  
Robin D. Hughes ◽  
Roger Williams
Keyword(s):  
Tumour Necrosis Factor ◽  
Normal Control ◽  
Fulminant Hepatic Failure ◽  
Hepatic Failure ◽  
Tumour Necrosis ◽  
Neutralization Capacity ◽  
Control Subjects ◽  
Significant Difference ◽  
Necrosis Factor

1. Soluble tumour necrosis factor receptors released into the circulation inhibit the effects of excess tumour necrosis factor-α and represent an important protective response. 2. In this study we have measured the levels of tumour necrosis factor and soluble tumour necrosis factor receptors p55 and p75 in the plasma of 10 patients with fulminant hepatic failure and 10 healthy control subjects. The capacity of the plasmas at varying dilutions to inhibit the biological activity of 1000 pg/ml of recombinant tumour necrosis factor in a tumour necrosis factor cytotoxicity assay in vitro was also determined. 3. The mean plasma levels of tumour necrosis factor in patients with fulminant hepatic failure (48.4 ± 10.9 pg/ml) were significantly increased compared with normal control subjects (6.1 ± 1.04 pg/ml, P < 0.01). Plasma soluble tumour necrosis factor receptors p55 and p75 were also significantly elevated in patients with fulminant hepatic failure (18.16 ± 9.94 ng/ml and 16.06 ± 9.93 ng/ml respectively) when compared with normal control subjects (1.28 ± 0.24 ng/ml and 1.62 ± 0.91 ng/ml, P < 0.001). 4. Fulminant hepatic failure plasma had a much lower capacity to inhibit tumour necrosis factor bioactivity in vitro, with a statistically significant difference between the inhibitory capacity of the fulminant hepatic failure and normal plasma seen at plasma dilutions of 1:5 and 1:20 (P < 0.05). 5. The reduced tumour necrosis factor neutralization capacity observed in fulminant hepatic failure, despite the increased levels of soluble tumour necrosis factor receptors, suggests enhanced susceptibility to the potential deleterious effects of tumour necrosis factor in fulminant hepatic failure.

In Vitro Cell-Mediated Immunologic Assay for Cow's Milk Allergy

PEDIATRICS ◽  
1980 ◽  
Vol 66 (3) ◽  
pp. 399-402
Author(s):  
Azaria Ashkenazi ◽  
Stanley Levin ◽  
Dalia Idar ◽  
Ayala Or ◽  
Ian Rosenberg ◽  
...  
Keyword(s):  
Normal Control ◽  
Acute Gastroenteritis ◽  
Milk Protein ◽  
Cow’S Milk ◽  
Milk Allergy ◽  
Cow's Milk ◽  
Control Subjects ◽  
Β Lactoglobulin ◽  
In Infants And Children

The production of a lymphokine, the leukocyte-migration-inhibition factor (LIF), by peripheral blood lymphocytes in response to an in vitro challenge with bovine β-lactoglobulin was assayed in infants and children suspected of having allergy to cow's milk protein. of the patients studied, 24 had cow's milk allergy, 24 were normal control subjects, 18 had recovered from milk allergy, 10 were newborns, and 10 were babies suffering from acute gastroenteritis. All patients with milk allergy demonstrated significant LIF production in response to β-lactoglobulin (23.5% ± 6.4%). In the normal control subjects, LIF was 3.1% ± 4.3% (P &lt; .0005). Only two of the 24 control subjects and two of the ten newborns had high-normal values bordering on the positive. None of the ten babies with acute gastroenteritis gave a positive response. Most of the children who had recovered from milk allergy and were ingesting cow's milk had negative assays. This cell-mediated immune assay is shown to be a reliable test for the diagnosis of sensitivity to milk protein in infants and children, and for determining dietary treatment and when this treatment can be safely terminated. In most cases, its use should eliminate the need for the potentially dangerous and ethically questionable provocation test, as well as the need for repeated intestinal biopsies.

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