Biomedical subjects

S Francavilla

Publications and source records attributed to S Francavilla.

At least 37 records · Page 2Linked to original sources

PubMed1997

Endothelin-1 in diabetic and nondiabetic men with erectile dysfunction.

PURPOSE: We evaluated plasma concentration of endothelin-1 in diabetic and nondiabetic men complaining of erectile dysfunction, and the variation of endothelin-1 in cavernous body blood during intracavernous injection of prostaglandin E1. MATERIALS AND METHODS: We evaluated plasma concentrations of endothelin-1 in venous blood of 20 men with erectile dysfunction, 10 with and 10 without diabetes. Plasma concentration of endothelin-1 was also evaluated in the cavernous body blood of the 20 men with erectile dysfunction, during erection induced by intracavernous injection of 10 micrograms prostaglandin E1. A severe vasculogenic component of erectile dysfunction was excluded in all patients. RESULTS: Basal plasma concentration of endothelin-1 in the cubital vein was increased in nondiabetic (1.13 +/- 0.4 pg./ml.) and in diabetic (1.80 +/- 0.2 pg./ml.) patients with erectile dysfunction, compared to control men (0.64 +/- 0.1 pg./ml.) (p < 0.0005 and p < 0.0001, respectively), and in diabetic compared with nondiabetic patients (p < 0.002). No difference and close correlation were observed in the concentration of endothelin-1 in the cavernous body blood evaluated 5 minutes and 30 minutes after injection of prostaglandin E1 (r = 0.89, p < 0.0001, y = 0.98 x + -0.066). The concentration of endothelin-1 in the cavernous body blood evaluated 30 minutes after injection of prostaglandin E1 did not show any difference compared to peripheral venous concentration of the peptide in the 2 patient groups. Concentrations of endothelin-1 in the peripheral vein and the cavernous body blood were not different in patients with a full erection compared with incomplete penis erection after injection of prostaglandin E1 in the cavernous body.

Adult↗

PubMed1996

Chromatin defects in normal and malformed human ejaculated and epididymal spermatozoa: a cytochemical ultrastructural study.

Cytochemical defects in chromatin were examined by transmission electron microscopy (TEM) after the staining by alcoholic phosphotungstic acid (PTA) of normal and malformed ejaculated spermatozoa from 35 male partners of infertile couples, and in six sperm samples retrieved from the caput epididymidis of men affected by obstructive azoospermia. PTA staining was also analysed in normal ejaculates of fertile men after incubation of the washed spermatozoa with dithiothreitol (DTT) to reduce disulfides to thiols, or with DTT followed by iodoacetamide, a blocking agent for thiol groups. PTA stained 63 (27-100)% of malformed heads and 25 (10-100)% of normal sperm heads (median (range) n = 35; P = 0.0001, Wilcoxon matched pairs test). The percentage of normal heads stained by PTA was negatively correlated with the percentage of heads of normal form, with condensed chromatin and a normal acrosome (Spearman r = 0.75; P = 0.0001), and positively correlated with the percentage of malformed heads after conventional TEM analysis (Spearman r 0.60; P = 0.0001). Staining with PTA in normal heads was not correlated with the presence of non-condensed chromatin in otherwise normal sperm heads evaluated by conventional TEM analysis. In spermatozoa recovered from the caput epididymidis, 15% of normal heads were stained with PTA, significantly fewer than in ejaculated sperm samples (P = 0.014). The reduction of disulfides to thiols was associated with PTA staining of all normal heads, and this was prevented by incubation with iodoacetamide. We conclude that PTA staining of the nuclei of human ejaculated spermatozoa may indicate a defect of chromatin condensation, owing to an excess of free thiol groups. The lower percentage of normal epididymal sperm heads that stained with PTA in cases of obstructive azoospermia compared with ejaculated sperm may be related to an overoxidation of thils owing to the ageing of spermatozoa.

Chromatin↗

PubMed1996

Hürthle cell adenoma of the thyroid: in 32 consecutive cases.

Hürthle cell neoplasms of the thyroid gland are uncommon but potentially lethal lesions, the treatment of which is controversial because of a lack of information about their biological and clinical behaviour. Based on histological criteria Hürthle cell tumours cannot always be separated accurately into benign and malignant. Unexpected evolutions with malignant late recurrence of an adenoma previously labelled as benign have been reported. The authors reviewed the clinical and pathological features of 32 patients with Hürthle cell adenomas. The results suggest that total thyroidectomy 'de principe' is not necessary and that some electron microscopy criteria are useful to understand the nature and to predict the biological deportment of Hürthle cell adenomas.

Adenoma, Oxyphilic↗

PubMed1995

Early increase precedes a depletion of endothelin-1 but not of von Willebrand factor in cutaneous microvessels of diabetic patients. A quantitative immunohistochemical study.

Endothelin-1 (ET-1) is a vasoconstrictor peptide which is produced by endothelial cells. The subcellular distribution of ET-1 in human skin and the variation of immunostaining for ET-1 by light microscopy in skin biopsies of diabetic patients have been analysed using immunohistochemistry and image analysis quantification. Skin biopsies were collected from 17 patients with type 1 diabetes of different durations and with presence or absence of microangiopathy in the retina; skin biopsies of healthy subjects were utilized as controls. The distribution of ET-1 immunoreactivity (IR) at both light and electron microscopy was compared to that of von Willebrand factor (vWf), a general marker of total cutaneous microvessels. Immunohistochemistry revealed that in controls the distribution of immunostaining was similar for ET-1 and vWf, being localized to microvessels in all areas of the skin. However, at the electron microscopical level ET-1-IR was localized in the endothelial cytoplasm rather than in specific organelles, while vWf immunostaining was associated with Weibel-Palade bodies. ET-1-IR was observed in 4/8 (50 per cent) biopsies from healthy subjects; this increased to 81.8 per cent in biopsies of patients affected by diabetes for less than 10 years and decreased to 16.6 per cent in patients with diabetes for more than 10 years. Quantification of ET-1 staining showed a significant decrease of ET-1-IR in patients affected by diabetes for more than 10 years compared with those affected by diabetes for less than 10 years (P < 0.05). Also, the percentage of biopsies showing positive ET-1 staining was lower in patients with retinopathy than in patients without retinopathy. On the contrary, vWf-IR was observed in all skin specimens and its quantification showed no differences between diabetic patients and controls. These changes are not related to variations in the number of blood vessels, and it is suggested that they reflect a possible functional alteration of the endothelial cells during diabetes.

Adolescent↗

PubMed1994

Analysis of protein kinase C requirement for exocytosis in permeabilized rat basophilic leukaemia RBL-2H3 cells: a GTP-binding protein(s) as a potential target for protein kinase C.

The role of protein kinase C in calcium-dependent exocytosis was investigated in permeabilized rat basophilic leukaemia cells. When protein kinase C was down-regulated by phorbol myristate acetate (1 microM for 3-6 h) or inhibited by pharmacological agents such as calphostin C (1 microM) or a protein kinase C-specific pseudo-substrate peptide inhibitor (100-200 microM), cells lost the ability to secrete in response to 10 microM free Ca2+. In contrast, a short treatment (15 min) with phorbol myristate acetate, which maximally activates protein kinase C, potentiated the effects of calcium. Biochemical analysis of protein kinase C-deprived cells indicated that loss of the Ca(2+)-induced secretory response correlated with disappearance of protein kinase C-alpha. In addition, at the concentrations effective for exocytosis, calcium caused translocation of protein kinase C-alpha to the membrane fraction and stimulated phospholipase C, suggesting that, in permeabilized cells, protein kinase C can be activated by calcium through generation of the phospholipase C metabolite diacylglycerol. The delta, epsilon and zeta Ca(2+)-independent protein kinase C isoenzymes were insensitive to phorbol myristate acetate-induced down-regulation and did not, as expected, translocate to the particulate fraction in response to calcium. Interestingly, secretory competence was restored in cells depleted of protein kinase C or in which protein kinase C itself was inhibited by non-hydrolysable GTP analogues, but not by GTP, suggesting that protein kinase C might regulate the ability of a G protein(s) directly controlling the exocytotic machinery to be activated by endogenous GTP.

Amino Acid Sequence↗

PubMed1994

Impaired hamster egg penetration by human sperm from ejaculates with low acrosin activity but otherwise normal.

OBJECTIVE: To determine if a low acrosin activity in otherwise normal ejaculate from infertile patients is associated with an impairment of sperm functions involved in the hamster egg penetration. SETTING: A tertiary care center, the Andrology Clinic, Department of Internal Medicine, University of L'Aquila. PATIENTS: Nine infertile patients with low acrosin activity in otherwise normal ejaculate (including normal immunoreactivity for acrosin) were studied; nine fertile men served as a control group. The two groups were homogeneous for seminal parameters. INTERVENTIONS: The hamster egg penetration assay and the acrosome reaction rate assessment were performed on capacitated sperm suspensions in basal conditions and after ionophore challenge. MAIN OUTCOME MEASURES: The penetration rate, the penetration index, and the acrosome reaction rate were measured and compared between the groups. RESULTS: No penetration was achieved in seven patients and a low penetration was achieved in two cases. The difference with the control group was significant. The ionophore challenge was associated to penetration of hamster eggs in seven of nine patients, but the penetration index was significantly lower than the controls. Acrosin activity was correlated to hamster egg penetration. Both spontaneous and induced acrosome reaction rate were similar in the two groups. CONCLUSIONS: A low sperm acrosin activity in otherwise normal ejaculate is associated with an impaired hamster egg penetration. This impairment does not seem to be due to altered dynamics of acrosome reaction.

Acrosin↗

PubMed1994

Sperm-zona pellucida binding of human sperm is correlated with the immunocytochemical presence of proacrosin and acrosin in the sperm heads but not with the proteolytic activity of acrosin.

OBJECTIVE: To determine whether the sperm-zona pellucida (ZP) binding is related to the presence of immunoreactivity for proacrosin and acrosin and/or to the proteolytic activity of acrosin. SETTING: The Andrology Clinic, University of L'Aquila, Italy. PATIENTS: Thirty-five infertile couples and 15 men of proven fertility. INTERVENTIONS: Salt-stored unfertilized oocytes after IVF were inseminated with a mixture of equal numbers of test and fertile donor sperm after swim-up selection, respectively labeled with fluorescein or rhodamine. Total acrosin activity, the percent of sperm immunostained for proacrosin and acrosin, and the percent of sperm with oval heads were evaluated in fresh semen and after swim-up selection. MAIN OUTCOME MEASURES: Three zonae were used for each patient and sperm-ZP binding ratio (ZP ratio) was calculated as the total number of test sperm bound to ZP divided by the total number of control sperm bound to ZP. The ZP ratio was compared with the percent of live sperm immunostained for proacrosin and acrosin, with total acrosin activity and with the percent of sperm with oval heads after swim-up selection. RESULTS: The sperm-ZP binding ratio was correlated positively with the percent of sperm immunostained for proacrosin and acrosin and with the percent of sperm with oval heads, but not with acrosin activity. Ejaculates with immunostaining for proacrosin and acrosin > or = 55% of sperm (the mean value of infertile couples) and acrosin activity < 24 muIU/10(6) sperm (the mean value of infertile couples) (n = 8) had a ZP ratio > or = 0.5, whereas ejaculates with low immunostaining for proacrosin and low acrosin activity (n = 12) had a ZP ratio < 0.5. The difference between the ZP ratio of the two groups was highly significant. CONCLUSIONS: The ZP binding is related to the immunocytochemical presence of proacrosin and acrosin but not to the proteolytic activity of acrosin in human sperm, suggesting that egg recognition and proteolytic activity are independent functions of proacrosin and acrosin.

Acrosin↗

PubMed1993

Circumferential choledochoplasties with autologous venous and arterial grafts.

Circumferential choledochoplasties with vascular grafts have rarely been attempted either experimentally or in clinical practice. In this study, choledochoplasties using autologous venous and arterial grafts were performed in rats. Sixty-four rats were randomly selected into five treatment groups: A) venous interpositional graft replacement of a choledochus gap without a stent; B) venous graft with prolene stent; C) venous graft with polyethylene stent; D) arterial graft; E) a control group with simple resection between ligatures in the choledochus. The operative mortality in treatment groups B, C, D, and E, was 0, and 13% in group A. At 12 weeks follow-up, all the rats in group E had died, whereas, 52.2% (P < .05) of the rats in group A, 30% of the rats in group B, 57% of the rats in group C, and 92.8% of the rats in group D survived treatment. Surviving animals were sacrificed at 3 months for further examination. The morphology and caliber of the common bile duct of these rats were normal in 25% of the rats in group A, 33% of the rats in group B, 25% of the rats in group C, and 84.6% of the rats in group D. Proximal dilations were found in the rats presenting with abnormal morphology. The dilations were less marked in the group treated by arterial choledochoplasties. Laboratory and clinical cholestatic parameters were within normal ranges in the presence of common bile duct dilations less than four times the normal duct caliber.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Early increase precedes a depletion of VIP and PGP-9.5 in the skin of insulin-dependent diabetics--correlation between quantitative immunohistochemistry and clinical assessment of peripheral neuropathy.

Diabetic neuropathy affects both sensory and autonomic peripheral nerve fibres. Vasoactive intestinal polypeptide (VIP) is present in autonomic fibres which modulate sweat secretion, while calcitonin gene-related peptide (CGRP) is localized to cutaneous sensory fibres. In this study, immunohistochemistry and image analysis were used to assess changes of VIP and CGRP, and of the pan-neuronal marker protein gene-product (PGP)-9.5, in skin biopsies of 18 patients affected by type 1 diabetes (age range 18-46 years) and from seven aged-matched controls. Patients were divided into three groups: group 1 (n = 6), with diabetes for 6 months to 3 years; group 2 (n = 5), with the disease for 5-10 years; and group 3 (n = 7), with diabetes for more than 10 years. VIP immunoreactivity (IR) and PGP-9.5-IR were significantly reduced around sweat glands (P < 0.005) in groups 2 and 3. Epidermal CGRP-IR and PGP-9.5-IR were significantly reduced in group 3 (P < 0.05). Twenty-eight per cent (5/18) of all patients showed high VIP-IR around sweat glands (> 95 per cent confidence limits of controls) and all of these patients had diabetes for less than 3 years. Conversely, 55 per cent (10/18) of patients had low VIP-IR (< 5 per cent confidence limit of controls). The latter, compared with the former, showed a significantly longer duration of diabetes (Fisher exact test P = 0.002), presence of clinical autonomic neuropathy (Fisher exact test P = 0.04), and a reduced sural nerve conduction velocity (Fisher exact test P = 0.04). These results suggest that quantitative immunohistochemical analysis of peptide-containing cutaneous nerves allows an objective evaluation of nerve fibre alterations at early stages of diabetes than is currently possible with neurophysiological functional tests.

Adolescent↗

PubMed1993

Selective involvement of monocytes by acquired myeloperoxidase deficiency in a case of chronic myelomonocytic leukemia.

The authors describe a case of chronic myelomonocytic leukemia in which a myeloperoxidase (MPO) deficiency of circulating monocytes was first detected by automated differential cell counting, and subsequently confirmed by cytochemical and immunocytochemical investigations. MPO activity in neutrophil granulocytes from the same case was found to be normal. MPO deficiency in monocytes appeared to be associated with impaired phagocytic capacity and, based on the results of immunophenotypic and ultrastructural studies, was most likely attributable to a partial maturation arrest of monocytes. The present case suggests that MPO deficiency in myelodysplastic syndromes may have its origin in a number of different pathogenetic mechanisms.

Aged↗

PubMed1992

Postnatal development and distribution of peptide-containing nerves in the genital system of the male rat. An immunohistochemical study.

The distribution and relative density of peptide-containing nerves was studied in the rat in order to assess the progression of neuronal changes during the postnatal development of the male genital system from the prepubertal age to adulthood. Testis, caput and cauda epididymis, ductus deferens, seminal vesicles, prostate and penis from 8-, 20-, 38-, and 70-day-old rats were sectioned and were immunostained with antisera to the neuropeptides calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY), and to a general neuronal marker, protein gene product 9.5 (PGP 9.5). The testicular parenchyma and caput epididymis did not show any immunoreactivity. Very scattered CGRP-containing nerves were present in 8-day-old rats; numerous VIP-, CGRP-, and NPY-peptide-containing nerves were observed in the cauda epididymis, ductus deferens, accessory glands and penis of 20-day-old rats. The number of nerves increased in 35-day-old rats while no changes were observed in more adult rats. A parallel increase was seen for the immunostain for PGP 9.5. These data suggest that peptide-containing nerves appear in the genital system after birth and reach a full development before the completion of puberty. Peptide-containing nerves were visible first in the interstitial area and then spread in the muscular coat of the ducts, glands and of the blood vessels. While CGRP- and NPY-containing nerves were distributed in the vicinity of the muscle cells, VIP-containing nerves were also observed in the subepithelial regions, suggesting a possible role of this neuropeptide in the control of epithelial functions.

Aging↗

PubMed1992

Sperm acrosin activity and fluorescence microscopic assessment of proacrosin/acrosin in ejaculates of infertile and fertile men.

OBJECTIVE: To compare biochemically active with immunoreactive sperm acrosin in fertile and infertile men. SETTING: This study was conducted in a tertiary care center, the Andrology Clinic, Department of Internal Medicine, University of L'Aquila. PATIENTS: We evaluated the males in 40 infertile couples with no recognized cause of female infertility and 20 fertile men. INTERVENTIONS: Ejaculates were collected under standardized conditions of abstinence. MAIN OUTCOME MEASURES: Total sperm acrosin activity was measured on a spectrophotometer in washed sperm stored at -80 degrees C for 1 to 6 days. The percent of spermatozoa immunostained by an antiserum against proacrosin/acrosin by indirect immunofluorescence (IFL) was determined on methanol fixed sperm smears. RESULTS: Biochemically active acrosin was correlated to immunoreactive acrosin (P = 0.0028), and both were inversely correlated to the percent of spermatozoa with an abnormal head (P = 0.00024 for acrosin activity and P = 0.0013 for IFL). Biochemically active and immunoreactive acrosin were lower in infertile compared with fertile men (P = 0.0012 and P = 0.0009, respectively). Sixty-eight percent of ejaculates with an acrosin activity lower than the limit value observed in fertile men showed a normal sperm morphology and a normal immunoreactivity for acrosin. CONCLUSIONS: A low sperm acrosin activity in teratospermic ejaculates is because of a lack or a defect of the immunogenic and functional domains of the protein. A low sperm acrosin in infertile men with normal semen parameters results from a possible functional defect of the enzyme that is immunohistochemically detected in spermatozoa.

Acrosin↗

PubMed1991

Effect of thyroid hormone on the pre- and post-natal development of the rat testis.

The relationship between thyroid function and testicular development in the rat was investigated. Hypothyroidism was induced during fetal or post-natal life by adding methimazole (MMI) to the drinking water of pregnant or lactating mothers. A group of newborn rats was treated with MMI and i.p. injections of L-tri-iodothyronine (L-T3). Hypothyroidism was shown by the reduced serum levels of total T3 and of total thyroxine (T4) in pregnant mothers and in pubertal rats. Testes were studied using light microscopy at 18 and 21 days post coitum or during puberty (21, 35 and 50 days after birth); serum levels of gonadotrophins were also evaluated in pubertal rats. Hypothyroidism had no effect on testicular development during fetal life and when induced in newborn rats it was associated at puberty with reduced serum levels of FSH and LH and with delayed maturation of the testis compared with control rats. The delay in maturation consisted of a reduction in the diameter of seminiferous tubules, and a reduction in the number of germ cells per tubule; this was associated with increased degeneration and arrested maturation of germ cells. In addition, Sertoli cells demonstrated retarded development, as indicated by a delay in the appearance of cytoplasmic lipids and in the development of a tubule lumen. Hormonal and morphological abnormalities were absent in rats treated with MMI plus L-T3. In conclusion, hypothyroidism occurring soon after birth caused reduced levels of gonadotrophins in the serum and a delay in pubertal spermatogenesis, possibly due to retarded differentiation of the Sertoli cells.

Animals↗

PubMed1990

Early increase in CGRP- and VIP-immunoreactive nerves in the skin of streptozotocin-induced diabetic rats.

We have previously shown depletion of nerves and neuropeptides in skin biopsies of diabetic patients, even in the absence of clinical signs and symptoms of sensory and autonomic neuropathy, but were unable to examine the changes occurring at an early stage of the disease. Therefore, the distribution and relative density of peptide-containing nerves was studied in streptozotocin-treated rats in order to assess the progression of neural changes in the initial stages of diabetes. Skin samples dissected from the lip and footpad of diabetic rats, 2, 4, 8 and 12 weeks after streptozotocin injection and age matched controls were sectioned and were immunostained with antisera to the neuropeptides substance P, calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY), and to a general neural marker, protein gene product 9.5 (PGP 9.5). No change was apparent in the distribution or relative density of immunoreactive cutaneous nerve fibres 2, 4 and 8 weeks after streptozotocin treatment. By 12 weeks there was a marked increase in the number of CGRP-immunoreactive fibres present in epidermis and dermis, and of VIP-immunoreactive fibres around sweat glands and blood vessels. A parallel increase was seen in nerves displaying PGP 9.5 immunoreactivity. No differences were detected in nerves immunoreactive for either substance P in the epidermis and dermis, and NPY around blood vessels. The alterations in the peptide immunoreactivities may be similar in the initial stages of human diabetes.

Animals↗

PubMed1990

Ontogenesis of the nuclear 3,5,3'-triiodothyronine receptor in the rat testis.

The aim of this study was to investigate the ontogenesis of the nuclear T3 receptor among the different cell types in the rat testis from fetuses at the 19th day of gestation and animals 1, 5, 15, 20, and 60 days after birth. Whole testis, tubular fraction, nontubular fractions, and Sertoli cells cultured in vitro or enriched in vivo by irradiation were used. The results demonstrate that high affinity, low capacity T3-binding sites are localized only in Sertoli cells; the binding specificity and affinity (Kd ranges from 0.8 +/- 0.2 to 2.6 +/- 0.4 nM) do not change significantly with the age of the animals and are comparable to those observed for T3 receptors in other mammalian tissues. In the whole testis, the concentration of receptors changes during gonadal development, being maximally expressed in the fetus (154.3 +/- 8.1 fg T3 bound/10(6) nuclei) and from 1 (203.4 +/- 10.9 fg T3 bound/10(6) nuclei) to 5 (185.3 +/- 15.1 fg T3 bound/10(6) nuclei) days of postnatal life, decreasing significantly at 15 and 20 days (65.4 +/- 2.0 and 57.9 +/- 1.9 fg T3 bound/10(6) nuclei, respectively) and being virtually absent in the adult. The same change in receptor concentration was found in Sertoli cells obtained by different techniques. This ontogenetic profile coincides with the pattern of Sertoli cell proliferation and differentiation, thus suggesting a role of thyroid hormones in the regulation of growth and maturation of the somatic cells of the seminiferous epithelium.

Animals↗

PubMed1990

Quantitative parameters of seminiferous epithelium in secretory and excretory oligoazoospermia.

Testicular biopsy specimens from infertile men (sperm count, less than 10(6)/ml) were evaluated on 1-micron thick sections, and counts of stem cells and differentiated spermatogonia, primary spermatocytes, early and late spermatids, and Sertoli cells were compared to counts in six fertile men. Biopsy specimens were also compared for the appearance of seminiferous tubule wall, blood vessels, and interstitium. Infertile men were grouped according to the following diagnoses: hypospermatogenesis (n = 5), spermatocyte arrest of spermatogenesis (n = 5), and obstruction of the genital tract (n = 7). A low productivity of spermatogenesis in cases of hypospermatogenesis appeared to be due to an exaggerated degeneration of primary spermatocytes and to a yield of abnormal spermatids. A block of meiosis in spermatocyte arrest was associated with a degeneration of primary spermatocytes and with a reduced number of staminal spermatogonia. Abnormal spermiogenesis was observed in cases of obstruction of the genital tract and was associated with an increase in stem cell spermatogonia. A thickening of seminiferous tubule and blood vessel walls could be responsible for the limited functional capacity of Sertoli cells, causing altered spermiogenesis in cases of excretory azoospermia. A severe primitive failure of Sertoli cells in secretory oligoazoospermia could account for a deranged maturation and degeneration of premeiotic and postmeiotic germ cells.

Adult↗

PubMed1990

Ultrastructure of fetal human gonad before sexual differentiation and during early testicular and ovarian development.

The development of the human gonad was investigated by light and transmission electron microscopy in 20 embryos and fetuses between 4.5 and 11.5 weeks of gestation, i.e. during the stages of sex-indifferent gonad, initial testicular and ovarian development. The gonadal blastema in 4.5-week-old embryos appeared formed by poorly differentiated somatic mesothelial cells, and by specialized germ cells (PGCs) with signs of ameboidism, cellular structures suggesting active protein biosynthesis and mitotic activity. The sexual differentiation of the gonads was clearly observed in 7-week-old embryos and involved at the same time the testis and the ovary. The former contained seminiferous cords formed by palisades of poorly differentiated Sertoli cells, which were segregated from the mesothelium by a rudimentary albuginea. The interstitial tissue at this age contained mesenchymal cells. Between 8 and 11.5 weeks of gestation, there was a synchronous cytodifferentiation of both Sertoli and Leydig cells. The latter acquired features of steroidogenic elements. The ovaries of 7-week-old fetuses contained packed ovigerous cords formed by somatic and germ cells (oogonia). The former embraced the oogonia with thin overlapping cytoplasm projections, and acquired features similar to those of cells in primary follicles, already at this early fetal age. At the same time the sexual differentiation of the gonads involved somatic and germ cells. In the female, the oogonia continued to show the main features they had during migration and colonization, including a high mitotic rate, signs of ameboidism and a developed apparatus for protein synthesis. On the contrary Gonocytes enclosed in the seminiferous cords progressively entered a quiescent phase characterized by a reduced mitotic rate, a decrease of endoplasmic reticulum and nucleolar complexity. The chronological relationship between the cytodifferentiation of Sertoli and Leydig cells, and changes of germ cells, suggest that somatic components of the testis may contribute to a male type of differentiation of germ cells from the very beginning of sexual differentiation.

Female↗

PubMed1989

Testicular changes after treatment with a GnRH analog (buserelin) in association with cyproterone acetate in men with prostatic cancer.

Twelve patients (age range: 53-78 years) with prostatic cancer were treated with Buserelin (1.2 mg/day) and cyproterone acetate (150 mg/day). Testicular biopsies performed after 13-96 weeks of treatment were compared to those obtained from 6 untreated men of similar age. Deranged spermatogenesis was observed in all but 1 treated patient. The appearance of immature Sertoli cells and atrophic Leydig cells suggests a condition of pharmacologic 'hypophysectomy'. The variable damage to the seminiferous epithelium and findings of an incomplete involution of Leydig cells suggested a decreased but still present testicular steroidogenesis.

Aged↗