Spermatogenesis is an intriguing but complicated biological process. However, many studies since the 1960s have focused either on the hormonal events of the hypothalamus-pituitary-testicular axis or morphological events that take place in the seminiferous epithelium. Recent advances in biochemistry, cell biology, and molecular biology have shifted attention to understanding some of the key events that regulate spermatogenesis, such as germ cell apoptosis, cell cycle regulation, Sertoli-germ cell communication, and junction dynamics. In this review, we discuss the physiology and biology of junction dynamics in the testis, in particular how these events affect interactions of Sertoli and germ cells in the seminiferous epithelium behind the blood-testis barrier. We also discuss how these events regulate the opening and closing of the blood-testis barrier to permit the timely passage of preleptotene and leptotene spermatocytes across the blood-testis barrier. This is physiologically important since developing germ cells must translocate across the blood-testis barrier as well as traverse the seminiferous epithelium during their development. We also discuss several available in vitro and in vivo models that can be used to study Sertoli-germ cell anchoring junctions and Sertoli-Sertoli tight junctions. An in-depth survey in this subject has also identified several potential targets to be tackled to perturb spermatogenesis, which will likely lead to the development of novel male contraceptives.

https://www.physiology.org/doi/pdf/10.1152/physrev.00009.2002

Cell Junction Dynamics in the Testis: Sertoli-Germ Cell Interactions and Male Contraceptive Development

Widely varied chemicals--including certain herbicides, plasticizers, drugs, and natural products--induce peroxisome proliferation in rodent liver and other tissues. This phenomenon is characterized by increases in the volume density and fatty acid oxidation of these organelles, which contain hydrogen peroxide and fatty acid oxidation systems important in lipid metabolism. Research showing that some peroxisome proliferating chemicals are nongenotoxic animal carcinogens stimulated interest in developing mode of action (MOA) information to understand and explain the human relevance of animal tumors associated with these chemicals. Studies have demonstrated that a nuclear hormone receptor implicated in energy homeostasis, designated peroxisome proliferator-activated receptor alpha (PPARalpha), is an obligatory factor in peroxisome proliferation in rodent hepatocytes. This report provides an in-depth analysis of the state of the science on several topics critical to evaluating the relationship between the MOA for PPARalpha agonists and the human relevance of related animal tumors. Topics include a review of existing tumor bioassay data, data from animal and human sources relating to the MOA for PPARalpha agonists in several different tissues, and case studies on the potential human relevance of the animal MOA data. The summary of existing bioassay data discloses substantial species differences in response to peroxisome proliferators in vivo, with rodents more responsive than primates. Among the rat and mouse strains tested, both males and females develop tumors in response to exposure to a wide range of chemicals including DEHP and other phthalates, chlorinated paraffins, chlorinated solvents such as trichloroethylene and perchloroethylene, and certain pesticides and hypolipidemic pharmaceuticals. MOA data from three different rodent tissues--rat and mouse liver, rat pancreas, and rat testis--lead to several different postulated MOAs, some beginning with PPARalpha activation as a causal first step. For example, studies in rodent liver identified seven "key events," including three "causal events"--activation of PPARalpha, perturbation of cell proliferation and apoptosis, and selective clonal expansion--and a series of associative events involving peroxisome proliferation, hepatocyte oxidative stress, and Kupffer-cell-mediated events. Similar in-depth analysis for rat Leydig-cell tumors (LCTs) posits one MOA that begins with PPARalpha activation in the liver, but two possible pathways, one secondary to liver induction and the other direct inhibition of testicular testosterone biosynthesis. For this tumor, both proposed pathways involve changes in the metabolism and quantity of related hormones and hormone precursors. Key events in the postulated MOA for the third tumor type, pancreatic acinar-cell tumors (PACTs) in rats, also begin with PPARalpha activation in the liver, followed by changes in bile synthesis and composition. Using the new human relevance framework (HRF) (see companion article), case studies involving PPARalpha-related tumors in each of these three tissues produced a range of outcomes, depending partly on the quality and quantity of MOA data available from laboratory animals and related information from human data sources.

PPARα Agonist-Induced Rodent Tumors: Modes of Action and Human Relevance

The evaluation of organ weights in toxicology studies is an integral component in the assessment of pharmaceuticals, chemicals, and medical devices. The Society of Toxicologic Pathology (STP) has created recommendations for weighing organs in GLP general toxicology studies lasting from 7 days to 1 year. The STP recommends that liver, heart, kidneys, brain, testes, and adrenal glands be weighed in all multidose general toxicology studies. Thyroid gland and pituitary gland weights are recommended for all species except mice. Spleen and thymus should be weighed in rodent studies and may be weighed in non-rodent studies. Weighing of reproductive organs is most valuable in sexually mature animals. Variability in age, sexual maturity, and stage of cycle in non-rodents and reproductive senescence in female rodents may complicate or limit interpretation of reproductive organ weights. The STP recommends that testes of all species be weighed in multidose general toxicology studies. Epididymides and prostate should be weighed in rat studies and may be weighed on a case-by-case basis in non-rodent and mouse studies. Weighing of other organs including female reproductive organs should be considered on a case-by-case basis. Organ weights are not recommended for any carcinogenicity studies including the alternative mouse bioassays. Regardless of the study type or organs evaluated, organ weight changes must be evaluated within the context of the compound class, mechanism of action, and the entire data set for that study.

https://journals.sagepub.com/doi/pdf/10.1080/01926230701595300

Society of Toxicologic Pathology position paper: organ weight recommendations for toxicology studies.

In contrast, the prostate is a rare site of tumor development in carcinogenesis bioassays in rodents (2,3) and in aging male laboratory rodents, with the exception of ventral prostatic neoplasms in some rat strains (4–9). Prostate cancer is also rare in male farm and companion animals, with the notable exception of the dog, which is the only species besides man that develops this malignancy. As will be discussed in this overview, steroid hormones can induce and can substantially enhance prostate carcinoma development in rodents, and this phenomenon has been exploited to further our knowledge about the involvement of hormonal factors and mechanisms in prostate cancer etiology. In this overview, the epidemiologic evidence for a role of steroid hormonal factors in prostate carcinogenesis is summarized first, followed by review of experimental data, a discussion of the possible mechanisms whereby steroid hormones, androgens as well as estrogens, may be involved in prostate cancer causation, and overall conclusions and suggestions for future research. As will be demonstrated, there is no lack of hypotheses about the role of steroid hormones in prostate cancer etiology, but the available data are often contradictory and incomplete, and an in-depth overall mechanistic understanding of how steroid hormonal factors are involved in prostate carcinogenesis is very limited.

/pdf/the-role-of-steroid-hormones-in-prostate-carcinogenesis-3g8apgkkxa.pdf

The role of steroid hormones in prostate carcinogenesis.

Objectives To determine the effect of antibiotic prophylaxis on infective complications after transrectal needle biopsy of the prostate



Patients and methods Between June 1996 and September 1998, 231 patients who satisfied the inclusion and exclusion criteria entered the study; the patients were randomized into three groups Each patient underwent transrectal needle biopsy of the prostate after a cleansing enema at 06:00 hours Patients in group 1 (75) then received a placebo tablet twice a day for 3 days; those in group 2 (79) were given a single dose of ciprofloxacin (500 mg) and tinidazole (600 mg), while those in group 3 (77) were given the same combination twice a day for 3 days Urine cultures were obtained 48 h after the biopsy and blood cultures only from patients who developed fever The complications (categorized as infective or noninfective) occurring in the three groups were compared using the chi-square test



Results Noninfective complications included were lower urinary tract symptoms, rectal bleeding, haematuria and perineal pain The infective complications included urinary tract infection and fever There was no significant difference among the three groups in noninfective complications (27, 29 and 31 in groups 1–3, respectively) but the incidence of infective complications (19, six and eight, respectively) was significantly higher in group 1 (P = 0003) However, the difference was significant only for urinary tract infection (P = 001) and not for fever



Conclusions In selected patients a single dose of ciprofloxacin-tinidazole is adequate prophylaxis for transrectal needle biopsy of the prostate The present urinary infection rate was higher if no antibiotics were used Continuing the antibiotic prophylaxis for 3 days offered no benefit over single-dose prophylaxis

Antibiotic prophylaxis for transrectal needle biopsy of the prostate: a randomized controlled study.

The male reproductive system consists of external reproductive organs, penis and scrotum, and internal reproductive organs: testes, a duct system, and accessory glands. The adult, paired testes produce both male sex hormones (androgens) and sperm cells (spermatogenesis). Androgens, primarily testosterone, are necessary for development and maintenance of male behavioral and physical manifestations and for spermatogenesis.

W R Gomes

Papers

The Male Reproductive System