Javier Codesal

Cadmium chloride-induced dysplastic changes in the ventral rat prostate: An immunohistochemical and quantitative study

Cadmium chloride is an environmental toxic that might be implicated in human prostate carcinogenesis. The study was directed: 1) to evaluate the immunoexpression of markers for cell proliferation, apoptosis, and resistance to apoptosis, and 2) to estimate the size of premalignant cell population in the preneoplastic changes induced in ventral prostates of rats treated with cadmium chloride administered in drinking water.

Quantification of cell types throughout the cycle of the human seminiferous epithelium and their DNA content

SummaryThe numbers of each different cell type in the human seminiferous epithelium were determined throughout the 6 stages of the cycle in both semithin and ultrathin sections obtained from 15 young adult men with normal testicular histology. Up to 4 types of A spermatogonia (Ad, Ap, Al and Ac) were distinguished. In addition, the DNA nuclear content of seminiferous epithelium cells was determined on Feulgen-stained sections. Both Ad and Ap spermatogonia showed a 2c DNA content and were present in the 6 stages of the cycle, though their numbers decreased in stages III–V. Both Al and Ac spermatogonia showed a DNA content varying from 2c to 4c. Al spermatogonia were observed in stages III–V; their numbers plus those of Ad spermatogonia in these stages were similar to the numbers of Ad spermatogonia in the other stages lacking in Al spermatogonia. Ac spermatogonia appeared in stages III–VI and their numbers plus those of Ap spermatogonia in stages III–V were similar to the numbers of Ap spermatogonia in the other stages lacking in Ac spermatogonia. The results suggest that Ad spermatogonia are the stem cells. Some of them replicate their DNA; during this replication they appeared as Al spermatogonia. Al spermatogonia divide, giving rise to both Ad and Ap spermatogonia. Some Ap spermatogonia replicate their DNA; during this process they are transformed into Ac spermatogonia which divide, giving rise to B spermatogonia.

Correlation between spermatozoon numbers in spermiogram and seminiferous epithelium histology in testicular biopsies from subfertile men.

A new method for correlating testicular biopsies and spermiograms is proposed. The number of spermatogonia, round spermatids, and elongated spermatids per cross-sectioned tubule were calculated in the testes from 33 subfertile men and in 10 control normal testes. According to these quantitations, the testes in subfertile men were classified as testes with maturation arrest of spermatogenesis, testes with hypospermatogenesis, and testes with associated maturation arrest and hypospermatogenesis. A power regression curve correlating the number of elongated spermatids and sperm numbers in the spermiogram was performed.

Proliferative Activity of Human Spermatogonia from Fetal Period to Senility Measured by Cytophotometric DNA Quantification

The proliferative activity of human spermatogonia from the fetal period to senility was studied by means of cytophotometric quantification of the nuclear DNA content in histological sections. Proliferating spermatogonia that were replicating or had replicated their DNA (DNA content between 2.5c and 4.5c) were observed in all ages. The percentages of these spermatogonia were high (18.2%) in the second trimester of gestation, decreased in the third trimester (8.2%), maintained similar values in newborns (7.1%) and infants (9.5%), and increased markedly in 4- to 9-year-old children (22.5%). The latter percentage was maintained during puberty (20.1%), decreased significantly in adulthood (17.8%), and was higher in aging testes (25.2%). About 2% of spermatogonia with a DNA content higher than 4.5 c were observed from 4-15 years of age as well as in the testes of elderly men. Sertoli cells replicating their DNA were observed only in fetuses.

Effect of prolactin and bromocriptine on the population of prostate neuroendocrine cells from intact and cyproterone acetate-treated rats: stereological and immunohistochemical study.

This work deals with the quantification of serotonin‐immunoreactive prostate neuroendocrine cells (NECs) in rats exposed to prolactin in normal, cyproterone acetate‐exposed, and bromocriptine‐exposed animals to establish the possible influence of prolactin with or without androgenic blockade on this cell population. Thirty male peripubertal Sprague‐Dawley rats were grouped as controls (CT) and those treated with cyproterone acetate (CA), cyproterone acetate plus prolactin, cyproterone acetate plus bromocriptine, prolactin (PL), and bromocriptine (BC). The volume of ductal epithelium (Vep) and total number (NSER) of the NECs serotonin‐immunoreactive were measured. NECs were detected in the periurethral ducts. Compared to CT, Vep was increased in PL and BC and NSER was decreased in CA and increased in the prolactin or bromocriptine groups. The androgenic blockade decreases NSER in rat prostate; PL induces in normal and cyproterone acetate‐treated rats the increase of NSER; and BC exerts a local effect over the prostate similar to that described for PL. Anat Rec, 2007.

Multinucleate Leydig cells in normal human testes

Summary:  The number of mononucleate and multinucleate Leydig cells per unit area of the testis was determined in normal adult men using the peroxidase‐anti‐peroxidase method for testosterone detection. The results of this study indicate that the number of multinucleate Leydig cells increases markedly with age, whereas the total Leydig cell population decreases.

Significance of DNA quantification in testicular germ cell tumors

Summary. A cytophotometric quantification of DNA in tumor cells was performed in histological sections of orchidectomy specimens from 36 men with testicular germ cell tumors (TGCT), 7 of them showing more than one tumor type. Among the variants of seminoma (classic and spermatocytic) the lowest DNA content were in spermatocytic seminoma. With respect to non‐seminomatous tumors (yolk sac tumor, embryonal carcinoma, teratoma, and choriocarcinoma), choriocarcinomas showed the highest DNA content, and the lowest value was found in teratomas. No significant differences were found between the average DNA content of seminomas (all types) and non‐seminomatous tumors (all types). Both embryonal carcinoma and yolk sac tumor showed similar DNA content when they were the sole tumor and when they were found associated with other tumors. In this study, except for the 4 cases of teratoma and the case of spermatocytic seminoma, all TGCT examined did not show modal values of DNA content in the diploid range. Such an elevated frequency of aneuploidism in these tumors may be helpful for their diagnosis.

Effect of Prolactin on the Population of Epithelial Cells From Ventral Prostate of Intact and Cyproterone Acetate‐Treated Peripubertal Rats: Stereological and Immunohistochemical Study

The interactions between steroid and nonsteroid hormones in the prostate are of special interest during the growth phase of the gland. The purpose of this work is to study the influence of prolactin (PL), with or without androgenic blockade, on epithelial cells from peripubertal rat ventral prostate. Twenty male peripubertal Sprague‐Dawley rats were grouped as controls, or treated with cyproterone acetate (CA), CA plus PL (CA‐PL), or PL. The total number (N total) of epithelial cells, and their labeling indices to proliferative cell nuclear antigen (LI PCNA), apoptosis (LI apoptosis) and androgen receptors (LI AR) were measured. CA and PL treatment significantly decrease the N total, but the LI PCNA was unchanged. We have observed a greater LI apoptosis in pharmacologically castrated animals without PL than in the rats with androgenic blockade with PL. The LI AR does not change with CA treatment in the ventral region, but the PL significantly increases it. Androgenic blockade and PL decrease the number of epithelial cells from the ventral prostate. These changes are not attributable to the decrease of cell proliferation, rather to the increase of epithelial apoptosis. The increase of cells expressing AR after treatment with PL might be attributed to the decrease of testosterone secretion caused by the hyperprolactinemia. PL does not modulate the size of the ventral prostate in prepubertal rats. Anat Rec, 2009.

Number and DNA content of hypertrophic spermatogonia in normal and cryptorchid human testes

The number and the DNA content of hypertrophic spermatogonia were studied in normal and cryptorchid testes. The number of hypertrophic spermatogonia in cryptorchid testes is higher than in control testes at the same age. This finding suggests alterations in the spermatogonia of cryptorchid males. The results show a polyploid DNA content in more than 80% of hypertrophic spermatogonia in both normal and cryptorchid testes. There were hypertrophic spermatogonia with a DNA content between 2c and 4c (0.5%) and between 4c and 8c (9%). These spermatogonia might be cells in the S phase of the cell cycle.

Stereological Estimate of the Length of Microvessels and the Number, Proliferation and Apoptosis of Endothelial Cells in Prostate Cancer

Abnormal angiogenesis is a critical feature of many diseases, including cancers and their precursors. Although the association between prostate carcinogenesis and changes in microvascular architecture is well known, these changes are not well-documented from a quantitative point of view. The present work deals with stereological estimates of the number of quiescent and proliferative endothelial cells, and microvessel length in normal and prostate cancer tissues. Un- biased stereological measurements of numerical densities of proliferating cell nuclear antigen immunostained cells, non- proliferating endothelial cells, caspase 3 immunoreactive endothelial cells, and relative length (length density) of mi- crovessels, were performed in control and cancer specimens. There were no changes in either proliferation or apoptosis in carcinoma endothelial cells. A decrease of endothelial cell density, together with an increase of microvessel length den- sity, were detected in prostate cancer specimens. Therefore, the following conclusions can be drawn: a) The increase of angiogenetic activity in prostate carcinogenesis leads to an increment of the microvascular length; b) The amount of endothelial cells per vascular length decreases in prostate cancer; c) There is no decrease of endothelial apoptosis in cancer microvessels. d) The increase of the length den- sity of microvessels in prostate cancer is not directly associated to an enhancement of the endothelial proliferation; and e) The blood supply of epithelium was similar in both cancerous and normal prostate.