Testosterone nanoemulsion produced masculinized Nile tilapia (Oreochromis niloticus).

The objective of this work was to develop a food additive for the sex reversal of Nile tilapia (Oreochromis niloticus) based on a simple oil in water (O/W) nanoemulsion with testosterone propionate for incorporation into commercial feed. Oil screening and evaluation of the organoleptic and physicochemical characteristics were carried out to determine the best formulation. A palatability test was also performed. Sex reversal test was assayed using 5 experimental groups: negative control - macerated feed without hormone; free testosterone - macerated feed with 60 mg/kg of testosterone propionate diluted in ethanol; and macerated feed with testosterone propionate nanoemulsion at a concentration of 30, 60, and 90 mg/kg. Stable nanoemulsions (size 76-210 nm) with testosterone propionate were produced. All nanoemulsion-added feed was palatable to tilapia. We obtained sex reversal values of ≈65, 75, and 72% in the groups of 30, 60, and 90 mg/kg, respectively. We can conclude that the nanoemulsion showed promising results; it is capable of inducing sex reversal in tilapia, is suitable as a commercial product, and has the potential to promote safety for rural staff and reduce the environmental impact of hormones.

Effects of Early Life Exposure to Sex Hormones on Neurochemical and Behavioral Responses to Psychostimulants in Adulthood: Implications in Drug Addiction.

Early life exposure to sex hormones affects several brain areas involved in regulating locomotor and motivation behaviors. Our group has shown that neonatal exposure to testosterone propionate (TP) or estradiol valerate (EV) affected the brain dopamine (DA) system in adulthood. Here, we studied the long-lasting effects of neonatal exposure to sex hormones on behavioral and neurochemical responses to amphetamine (AMPH) and methylphenidate (MPD). Our results show that AMPH-induced locomotor activity was higher in female than male control rats. The conditioned place preference (CPP) to AMPH was only observed in EV male rats. In EV female rats, AMPH did not increase locomotor activity, but MPD-induced CPP was observed in control, EV and TP female rats. Using in vivo brain microdialysis, we observed that AMPH-induced extracellular DA levels were lower in nucleus accumbens (NAcc) of EV and TP female rats than control rats. In addition, MPD did not increase NAcc extracellular DA levels in EV rats. Using in vivo fast-scan cyclic voltammetry in striatum, MPD-induced DA reuptake was higher in EV than control rats. In summary, our results show that early life exposure to sex hormones modulates mesolimbic and nigrostriatal DA neurons producing opposite neurochemical effects induced by psychostimulant drugs in NAcc or striatum.

Previous short-term use of testosterone propionate enhances muscle hypertrophy in Wistar rats submitted to ladder-based resistance training.

To investigate the effects of the previous administration of testosterone propionate (TP) on the morphology of the gastrocnemius muscle of Wistar rats submitted to ladder-based resistance training (LRT). Twenty-eight rats were divided equally into groups: initial control (CI), 4-week TP (CT4), 4-week TP + LRT (TRT), and placebo + LRT (RT). The rats from the CT4 and TRT groups were treated with TP for four weeks (10 mg/kg/week). TRT and RT trained for ten weeks. The rodents were euthanized at the end of the experiment, and gastrocnemius muscle, prostate, and left and right testicles were collected. There was no statistical difference between the RT and TRT for final volume load. The prostate mass of the TRT and RT groups was statistically heavier than the CT4 group (P < 0.01). The TRT group's prostate/body mass ratio was statistically different from the CT4 group (P < 0.05). The TRT group was shown to have larger type I, type II, and mean fCSA fibers than all other groups (P < 0.001). Regarding the nuclei/fiber ratio (N/f), the CT4, RT, and TRT groups had higher values than CI (P < 0.01). In addition, the RT group showed a higher N/f ratio than CT4 (P < 0.001) but lower than TRT (P < 0.001). In conclusion, short-term TP administration before resistance training can elicit a greater N/f ratio and size of the mean fCSA of the Gastrocnemius muscle of young adult Wistar rats than resistance training alone.

Topical estrogen, testosterone, and vaginal dilator in the prevention of vaginal stenosis after radiotherapy in women with cervical cancer: a randomized clinical trial.

BACKGROUND: We aimed to evaluate the effects of different therapeutic options to prevent the evolution of vaginal stenosis after pelvic radiotherapy in women with cervical cancer. METHODS: open-label randomized clinical trial of 195 women, stage I-IIIB, aged 18-75 years, using topical estrogen (66), topical testosterone (34), water-based intimate lubricant gel (66), and vaginal dilators (29) to assess the incidence and severity of vaginal stenosis after radiotherapy at UNICAMP-Brazil, from January/2013 to May/2018. The main outcome measure was vaginal stenosis assessed using the Common Terminology Criteria for Adverse Events (CTCAE) scale and percental changes in vaginal volume. The women were evaluated at four different times: shortly after the end of radiotherapy, and four, eight, and 12 months after the beginning of the intervention. Statistical analysis was carried out using Symmetry test, Kruskal-Wallis test and multiple regression. RESULTS: the mean age of women was 46.78 (±13.01) years, 61,03% were premenopausal and 73,84% had stage IIB-IIIB tumors. The mean reduction in vaginal volume in the total group was 25.47%, with similar worsening in the four treatment groups with no statistical difference throughout the intervention period. There was worsening of vaginal stenosis evaluated by CTCAE scale after 1 year in all groups (p < 0.01), except for the users of vaginal dilator (p = 0.37). CONCLUSIONS: there was a reduction in vaginal volume in all treatment groups analyzed, with no significant difference between them. However, women who used vaginal dilators had a lower frequency and severity of vaginal stenosis assessed by the CTCAE scale after one year of treatment. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials, RBR-23w5fv . Registered 10 January 2017 - Retrospectively registered.

Determination of Steroids in Bovine Serum: Validation of a Reliable LC-MS/MS Method and In Vivo Studies with Boldenone Undecylenate and Testosterone Propionate.

Serum analysis has received much attention in regulatory analysis of food-producing animals, especially for anabolic steroids. The possibility of confirming the parent drugs with minimum metabolization enables the detection of intact steroid esters, whose identification represents unequivocal proof of drug administration. This work involved the development and validation of a quantitative LC-MS/MS method to determine 30 steroids and steroid esters in bovine serum. Sensitivity was improved using microwave-assisted chemical derivatization with methoxyamine hydrochloride. The validation was successfully conducted in accordance with the Decision 657/2002/EC guidelines. An in vivo experiment was performed on 12 crossbred steers in which two commercial formulations containing boldenone undecylenate and testosterone propionate were administrated via intramuscular injections. The samples were collected over a period of 120 days, in which both intact esters were identified within 11 days postadministration. 17ß-Boldenone was observed after 92 days for 2 steers and 56 days for the other animals. The applicability of a cut-off level to the ratio between 17ß-testosterone and epitestosterone was evaluated in an attempt to differentiate testosterone abuse from endogenous production. It could be observed that a calculated ratio above this level is strong evidence of drug administration, although a high false-negative rate was obtained.

Supraphysiological Levels of Testosterone Induce Vascular Dysfunction via Activation of the NLRP3 Inflammasome.

Background: Both supraphysiological and subphysiological testosterone levels are associated with increased cardiovascular risk. Testosterone consumption at supraphysiological doses has been linked to increased blood pressure, left ventricular hypertrophy, vascular dysfunction, and increased levels of inflammatory markers. Activation of the NLRP3 inflammasome contributes to the production of proinflammatory cytokines, leading to cardiovascular dysfunction. We hypothesized that supraphysiological levels of testosterone, via generation of mitochondrial reactive oxygen species (mROS), activates the NLRP3 inflammasome and promotes vascular dysfunction. Methods: Male, 12 week-old C57Bl/6J (WT) and NLRP3 knockout (NLRP3-/-) mice were used. Mice were treated with testosterone propionate [TP (10 mg/kg) in vivo] or vehicle for 30 days. In addition, vessels were incubated with testosterone [Testo (10-6 M, 2 h) in vitro]. Testosterone levels, blood pressure, vascular function (thoracic aortic rings), pro-caspase-1/caspase-1 and interleukin-1ß (IL-1ß) expression, and generation of reactive oxygen species were determined. Results: Testosterone increased contractile responses and reduced endothelium-dependent vasodilation, both in vivo and in vitro. These effects were not observed in arteries from NLRP3-/- mice. Aortas of TP-treated WT mice (in vivo), as well as aortas from WT mice incubated with testo (in vitro), exhibited increased mROS levels and increased caspase-1 and IL-1ß expression. These effects were not observed in arteries from NLRP3-/- mice. Flutamide [Flu, 10-5 M, androgen receptor (AR) antagonist], carbonyl cyanide m-chlorophenyl hydrazone (CCCP, 10-6 M, mitochondrial uncoupler) and MCC950 (MCC950, 10-6 M, a NLRP3 receptor inhibitor) prevented testosterone-induced mROS generation. Conclusion: Supraphysiological levels of testosterone induce vascular dysfunction via mROS generation and NLRP3 inflammasome activation. These events may contribute to increased cardiovascular risk.

Determination of steroids in bovine hair: Validation of a microwave-assisted chemical derivatization method using liquid chromatography-tandem mass spectrometry and in vivo studies.

Hair analysis has attracted great attention in the regulatory analysis of food-producing animals, particularly due to the wider detection window of veterinary drugs in this matrix and also the possibility of confirming parent drugs with minimum metabolization. This work involved the development and validation of a quantitative liquid chromatography-tandem mass spectrometry method to determine 25 steroids and steroid esters in bovine hair. Sensitivity was improved using a fast and effective microwave-assisted chemical derivatization with methoxyamine hydrochloride. The validation was conducted in accordance with the Decision 657/2002/EC guidelines. An animal experimentation procedure was performed on 12 bovine animals in which two commercial formulations containing boldenone undecylenate and testosterone propionate were administrated via intramuscular injections on the neck. The samples were collected for 78 days in which the detection of the administrated analytes was only observed near the application sites. For some of the monitored days, no analyte was detected on the neck area. Since the migration of the analytes was not observed in areas other than the application site, false-negative results should be carefully considered when monitoring animal hair samples.

"Prostate telocytes change their phenotype in response to castration or testosterone replacement".

Telocytes are CD34-positive cells with a fusiform cell body and long, thin cytoplasmic projections called telopodes. These cells were detected in the stroma of various organs, including the prostate. The prostate is a complex gland capable of undergoing involution due to low testosterone levels; and this condition can be reversed with testosterone replacement. Telocyte function in the mature prostate remains to be dermined, and it is not known whether telocytes can take place in tissue remodeling during prostate involution and regrowth. The present study employed structural, ultrastructural and immunohistochemical methods to investigate the telocyte's phenotypes in the ventral prostate (VP) from control (CT), castrated (CS) and testosterone replacement (TR) groups of adult male Wistar rats. Telocytes were found in the subepithelial, perimuscular and interstitical regions around glandular acini. Telocytes from CT animals have condensed chromatin and long and thin telopodes. In CS group, telocytes appeared quiescent and exhibited layers of folded up telopodes. After TR, telocytes presented loose chromatin, abundant rough endoplasmic reticulum and enlarged telopodes, closely associated with bundles of collagen fibrils. We called these cells "telocytes with a synthetic phenotype". As testosterone levels and glandular morphology returned toward to the CT group parameters, after 10 days of TR, these telocytes progressively switched to the normal phenotype. Our results demonstrate that telocytes exhibit phenotypic plasticity upon androgen manipulation and interact with fibroblast and smooth muscle cells to maintain glandular architecture in control animals and during tissue remodeling after hormonal manipulation.

Prenatal Androgenization of Ewes as a Model of Hirsutism in Polycystic Ovary Syndrome.

The main clinical feature associated with hyperandrogenism in polycystic ovary syndrome (PCOS) in humans is hirsutism, where hair increases its length, pigmentation, and particularly its diameter. Currently, it is not known whether PCOS animal models also exhibit changes in the hair. Therefore, the aim of this study was to explore the wool characteristics in sheep prenatally androgenized (PA) with testosterone propionate. After 4 and 13 months of life, wool was collected from the top of the shoulder of both females and males (both androgenized and controls). The offspring sheep were followed for up to 19 months of life to evaluate testosterone and androstenedione serum levels by ultra-high-performance liquid chromatography-tandem mass spectrometry, determine insulin and glucose response to intravenous glucose tolerance test, and address estrus cyclicity during the second breeding season. PA male animals showed a reduction in wool fiber diameter at 4 months of age compared with controls (P = 0.02) but not at 13 months, whereas PA females showed increased hair diameter at 13 months (P = 0.002), with no difference at 4 months. No substantial changes in other hair parameters (length, color, and medullation) were identified. In addition, increased levels of serum testosterone were observed in PA female sheep compared with controls at 12 months (P = 0.03). Our results indicate for the first time, to our knowledge, that changes in wool fiber diameter observed in PA ewes replicate, at the translational level, the increase in hair diameter in hirsute women with PCOS.

Neonatal programming with testosterone propionate reduces dopamine transporter expression in nucleus accumbens and methylphenidate-induced locomotor activity in adult female rats.

Research in programming is focused on the study of stimuli that alters sensitive periods in development, such as prenatal and neonatal stages, that can produce long-term deleterious effects. These effects can occur in various organs or tissues such as the brain, affecting brain circuits and related behaviors. Our laboratory has demonstrated that neonatal programming with sex hormones affects the mesocorticolimbic circuitry, increasing the synthesis and release of dopamine (DA) in striatum and nucleus accumbens (NAcc). However, the behavioral response to psychostimulant drugs such as methylphenidate and the possible mechanism(s) involved have not been studied in adult rats exposed to sex hormones during the first hours of life. Thus, the aim of this study was to examine the locomotor activity induced by methylphenidate (5mg/kg i.p.) and the expression of the DA transporter (DAT) in NAcc of adult rats exposed to a single dose of testosterone propionate (TP: 1mg/50µLs.c.) or estradiol valerate (EV: 0.1mg/50µLs.c.) at postnatal day 1. Our results demonstrated that adult female rats treated with TP have a lower methylphenidate-induced locomotor activity compared to control and EV-treated adult female rats. This reduction in locomotor activity is related with a lower NAcc DAT expression. However, neither methylphenidate-induced locomotor activity nor NAcc DAT expression was affected in EV or TP-treated adult male rats. Our results suggest that early exposure to sex hormones affects long-term dopaminergic brain areas involved in the response to psychostimulants, which could be a vulnerability factor to favor the escalating doses of drugs of abuse.

Avaliação histológica dos rins de camundongos suiços machos suplementados com propionato de testosterona e Tribulus terrestris L / Histological evaluation of kidneys from male swiss mice supplemented with testosterone propionate and Tribulus terrestris L

Introdução: a redução dos hormônios sexuais está associada à condição como a depressão e, nesse cenário, busca-se cada vez mais por tratamentos de suplementação com testosterona sintética, que possui muitos efeitos colaterais. O Tribulus terrestris L. (TT) é uma planta que supostamente possui compostos químicos similares ou análogos a testosterona. Objetivo: analisar a histologia dos rins de camundongos suíços machos suplementados com TT e propionato de testosterona (PT) Métodos: o procedimento utilizou 30 camundongos suíços machos divididos em 3 grupos, em que o grupo controle recebeu um veículo aquoso durante o experimento. O grupo testosterona recebeu 20mg/kg do fármaco PT e o grupo Tribulus recebeu 10 mg/kg do extrato das flores da planta TT. Após eutanásia, os rins foram retirados e emblocados em parafina para confecção das lâminas. Resultados e Discussão: em comparação ao grupo controle não foram evidenciadas diferenças histológicas. Conclusão: este estudo corrobora com o de Ghanbari (2016), que apresenta um suposto efeito antioxidante nos rins, não causando dano ao mesmo, e sim redução de disfunções renais, danos tubulares, apoptose e estresse oxidativo devido á flavonoides (substâncias encontradas na composição química da planta).

Introduction: the reduction of sex hormones is associated with condition such as depression and, in this scenario, it is increasingly sought for treatments of synthetic testosterone supplementation, which has many side effects. Tribulus terrestris L. (TT) is a plant that supposedly has chemical compounds similar to or analogous to testosterone. Objective: to analyze the histology of the kidneys of male Swiss mice supplemented with TT and testosterone propionate (PT) Methods: the procedure used 30 male Swiss mice divided into 3 groups, where the control group received an aqueous vehicle during the experiment. The testosterone group received 20 mg / kg of the drug PT and the Tribulus group received 10 mg / kg of the extract of the flowers of the TT plant. After euthanasia the kidneys were removed and placed in paraffin for the preparation of the slides. Results and Discussion: in comparison to the control group, no histological differences were found. Conclusion: this study corroborates that of Ghanbari (2016) which presents a supposed antioxidant effect in the kidneys, not causing damage to it, but reduction of renal dysfunctions, tubular damage, apoptosis and oxidative stress due to flavonoids (substances found in the composition chemistry of the plant).

Efficacy of vaginally applied estrogen, testosterone, or polyacrylic acid on vaginal atrophy: a randomized controlled trial.

OBJECTIVE: Vaginal atrophy is a common chronic condition among postmenopausal women that can affect their quality of life. Recent studies have evaluated new treatment alternatives for vaginal atrophy; however, few therapeutic options have been thoroughly evaluated. This study aimed to compare the effectiveness and adverse effects of estrogen, testosterone, polyacrylic acid, and placebo lubricant for the treatment of postmenopausal women with vaginal atrophy. METHODS: We conducted a randomized clinical trial with 80 postmenopausal women aged between 40 and 70 years who were being followed up at the Menopause Clinic of CAISM UNICAMP between November 2011 and January 2013. Women were randomly assigned to topical vaginal treatment with estrogen, testosterone, polyacrylic acid, and placebo lubricant, three times a week for 12 weeks. We used the vaginal maturation index, pH, vaginal health score, vaginal flora, laboratory tests, and ultrasound to evaluate changes of vaginal atrophy at baseline and after 6 and 12 weeks of treatment. RESULTS: After a 12-week treatment with topical estrogen and testosterone compared with the lubricant, an increased percentage of participants had vaginal pH less than 5, increased vaginal score, and an increase in the number of lactobacilli. Treatment with topical estrogen improved the vaginal maturation index and showed increased levels of estradiol in three women. No changes were observed in the endometrial evaluation of all treatment groups. CONCLUSIONS: After a 12-week treatment with testosterone and estrogen compared with placebo lubrication, there was a significant improvement in vaginal trophism in postmenopausal women with vaginal atrophy.

Programming of Dopaminergic Neurons by Neonatal Sex Hormone Exposure: Effects on Dopamine Content and Tyrosine Hydroxylase Expression in Adult Male Rats.

We sought to determine the long-term changes produced by neonatal sex hormone administration on the functioning of midbrain dopaminergic neurons in adult male rats. Sprague-Dawley rats were injected subcutaneously at postnatal day 1 and were assigned to the following experimental groups: TP (testosterone propionate of 1.0 mg/50 µL); DHT (dihydrotestosterone of 1.0 mg/50 µL); EV (estradiol valerate of 0.1 mg/50 µL); and control (sesame oil of 50 µL). At postnatal day 60, neurochemical studies were performed to determine dopamine content in substantia nigra-ventral tegmental area and dopamine release in nucleus accumbens. Molecular (mRNA expression of tyrosine hydroxylase) and cellular (tyrosine hydroxylase immunoreactivity) studies were also performed. We found increased dopamine content in substantia nigra-ventral tegmental area of TP and EV rats, in addition to increased dopamine release in nucleus accumbens. However, neonatal exposure to DHT, a nonaromatizable androgen, did not affect midbrain dopaminergic neurons. Correspondingly, compared to control rats, levels of tyrosine hydroxylase mRNA and protein were significantly increased in TP and EV rats but not in DHT rats, as determined by qPCR and immunohistochemistry, respectively. Our results suggest an estrogenic mechanism involving increased tyrosine hydroxylase expression, either by direct estrogenic action or by aromatization of testosterone to estradiol in substantia nigra-ventral tegmental area.

Perinatal exposure to androgen excess and the effects on the rat uterine estradiol responsiveness.

Androgen exposure during sexual development induces alterations in steroidal target tissues. The objective of this study was to evaluate the uterine responsiveness to estradiol after perinatal androgenization. Pregnant Wistar rats were exposed to corn oil or testosterone propionate at 0.05, 0.1, or 0.2 mg/kg from gestational day 12 until postnatal day 21. Female offspring was challenged with estradiol (E2 ) after weaning (0.4 mg/kg) and at adulthood (10 or 100 µg/day), when the pituitary response was also evaluated. At adulthood, control and 0.05 mg/kg groups presented a uterine weight increment when exposed to 100 µg/day of E2 , 0.1 mg/kg group only responded to 10 µg/day of E2 , and the 0.2 mg/kg group showed increased uterine weight at both doses. The pituitary weight was similarly increased after estradiol stimulation in all experimental groups. In conclusion, testosterone propionate exposure induced an abnormal stimulation of uterine tissue growth by estrogen stimulus without affecting pituitary response. More studies are needed to clarify whether these alterations are capable of impairing the reproductive capacity of the female tract. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1460-1468, 2016.

Effects of metformin on the adrenal cortex of androgenized rats.

OBJECTIVE: To evaluate the sex steroid profile and histomorphometry of the adrenal cortical zones of androgenized rats (wistar) with polycystic ovary syndrome treated with metformin. STUDY DESIGN: Thirty animals were divided into three groups: GC (regular estrous cycle), GPE (permanent estrus), and GPEM (permanent estrus + metformin 28 mg/kg for 50 days). At the end of this period, blood was collected for hormone measurement. The width of the adrenal cortical zones and the nuclear volumes were analyzed by histomorphometry. The ANOVA test was used in the statistical analysis. RESULTS: The adrenal glands of the androgenized animals were larger and more intensely vascularized than those of the other groups. The concentration of androstenedione in GPE was higher than that in the other groups (0.4 ± 0.1*>= 0.2 ± 0.1 = 0.2 ± 01, *p < 0.05). The width of the zona glomerulosa and of the zona reticularis and their nuclear volumes were greater in GPE compared to those of the other groups (GPE* > GPEM = GC, *p < 0.05). CONCLUSION: Metformin treatment may decrease the serum levels of androstenedione as well as the width and the nuclear volumes of the zona glomerulosa and of the zona reticularis in androgenized animals.

Neonatal androgenization-induced early endocrine-metabolic and ovary misprogramming in the female rat.

AIM: Androgen excess predisposes the organism to develop metabolic-endocrine and reproductive dysfunctions, among them the development of a phenotype resembling that of human Polycystic Ovary Syndrome (PCOS). METHODS: We analyzed the impact of a single neonatal (5day-old) testosterone propionate (TP; s.c. 1.25mg/female pup) dose on: a) several metabolic-endocrine activities and b) ovarian steroidogenic and granulosa cell (GC) functions and also follicular population in juvenile and adult TP and control (CT) rats. KEY FINDINGS: Compared to CT rats, TP animals were characterized by: a) accelerated growth, hyperadiposity and hyperleptinemia, b) very early (pre-weaning age) vaginal opening, c) hyperinsulinemia in adult life, d) dysfunctional ovarian steroidogenesis, e) conserved GC functionality in both juveniles (in vitro) and adults (in vivo), and f) estrous cycles arrested at estrus. Finally, histological studies of the ovaries indicated that in TP (vs. CT) rats: i) primary and antral follicle frequencies were 3- and 15-fold higher and lower, respectively, in juveniles and ii) secondary and atretic follicle frequencies were 3- and 5-fold lower and higher, respectively, in adults. Large cystic images without corpus luteum were observed in the ovaries from adult TP rats only. SIGNIFICANCE: Our results strongly suggest that transient neonatal hyperandrogenemia induced early misprogramming of metabolic-endocrine and ovarian (steroidogenesis/folliculogenesis) functions. Conversely, TP rats preserved their ovary GC endocrine function. Our results further support the high risk of developing ovarian hyperstimulation syndrome for infertile women with transient/chronic hyperandrogenemia (PCOS) subjected to assisted reproductive technologies.

Use of anabolic steroid altered the liver morphology of rats / El uso de esteroides anabólicos altera la morfología del hígado de ratas

The aim of this research was to investigate the effect of testosterone propionate administration in the liver of rats. The rats were divided in the following groups: Initial control (SC), Aged control (SE) and Anabolic group (SA). Testosterone propionate was administered three times per week during 16 weeks. Using morphoquantitative techniques, we quantified the volume densities of lobular and non-lobular parenchyma, area and number of nuclei of hepatocytes. The data were analyzed statistically using mean and standard deviation, ANOVA one-way and level of significance about p0.05. Our results showed an increase in capillaries, perisinusoidal spaces and biliary ducts in SE group compared to SC. SA group showed a decrease in hepatic cells, non-lobular volume density and hepatocytes nuclei area, but also an increase in capillaries, perisinusoidal spaces, biliary ducts, number of hepatocytes and non-hepatocyte nuclei compared to SC. We conclude that a direct toxicity may have occurred, with consequent loss of the cells.

El objetivo fue investigar el efecto de la administración de propionato de testosterona en el hígado de ratas. Las ratas se dividieron en los siguientes grupos: control inicial (CI), control de Edad (CE) y grupo anabólico (GA). El propionato de testosterona se administró tres veces por semana durante 16 semanas. Utilizando técnicas morfocuantitativas, determinamos las densidades de volumen del parénquima lobular y no lobular, área y número de núcleos de los hepatocitos. Los datos fueron analizados estadísticamente con la media y desviación estándar, la prueba de ANOVA de una vía y un nivel de significación p0,05. Nuestros resultados mostraron un aumento en los capilares, espacios perisinusoidales y conductos biliares en el grupo CE en comparación con CI. El GA mostró una disminución en las células hepáticas, la densidad de volumen no lobular y el área de los núcleos de hepatocitos, como también un aumento en los capilares, espacios perisinusoidales, conductos biliares, número de hepatocitos y núcleos no hepatocíticos en comparación AL CI. Concluimos que una toxicidad directa puede haber ocurrido, con la consiguiente pérdida de las células.

Perinatal androgenic exposure and reproductive health effects female rat offspring.

Environmental contaminants known as endocrine-disrupting chemicals (EDC) have been associated with adverse effects on reproductive processes. These chemicals may mimic or antagonize endogenous hormones, disrupting reproductive functions. Although preliminary studies focused on environmental estrogens, the presence of compounds with androgenic activity has also been described. This study examines exposure of female pregnant and lactating rats to low doses of androgens and assesses potential effects on female offspring. Pregnant Wistar rats were exposed to testosterone propionate (TP) at doses of 0.05, 0.1, or 0.2 mg/kg or corn oil (vehicle), subcutaneously, to determine influence on reproductive health of female offspring. There were two exposure groups: (1) rats treated from gestational day (GD) 12 until GD 20; and (2) animals treated from GD 12 until the end of lactation. Perinatal exposure to TP produced increased anogenital distance after birth and diminished height of uterine glandular epithelium at puberty in animals exposed to 0.2 mg/kg. However, these alterations were not sufficient to impair sexual differentiation and normal physiology of the female rat reproductive tract.

Excess androgen during perinatal life alters steroid receptor expression, apoptosis, and cell proliferation in the uteri of the offspring.

Exposure to environmental chemicals may contribute to reproductive disorders, especially when it occurs in critical periods of development. The female reproductive system can be a target for androgens derived from environmental contaminants or pathological conditions. The purpose of this study was to assess the long-term effects of androgens on uterine tissue after maternal exposure limited to the time of gestation and lactation. Pregnant Wistar rats were treated with testosterone propionate (TP) at 0.05 mg/kg, 0.1 mg/kg, 0.2 mg/kg or corn oil (vehicle), s.c., from gestational day 12 until the end of lactation. The results show changes in the pattern of expression of receptors for estrogen, progesterone, and androgen at all doses tested, and decreases in both apoptosis and cell proliferation indices at 0.1 and 0.2 mg/kg. We conclude that early TP exposure, under these experimental conditions, causes changes in cellular and molecular parameters that are essential for normal uterine function in the adult.

Pituitary and testis responsiveness of young male sheep exposed to testosterone excess during fetal development.

Prenatal exposure to excess testosterone induces reproductive disturbances in both female and male sheep. In females, it alters the hypothalamus-pituitary-ovarian axis. In males, prenatal testosterone excess reduces sperm count and motility. Focusing on males, this study tested whether pituitary LH responsiveness to GNRH is increased in prenatal testosterone-exposed males and whether testicular function is compromised in the testosterone-exposed males. Control males (n=6) and males born to ewes exposed to twice weekly injections of 30  mg testosterone propionate from days 30 to 90 and of 40  mg testosterone propionate from days 90 to 120 of gestation (n=6) were studied at 20 and 30 weeks of age. Pituitary and testicular responsiveness was tested by administering a GNRH analog (leuprolide acetate). To complement the analyses, the mRNA expression of LH receptor (LHR) and that of steroidogenic enzymes were determined in testicular tissue. Basal LH and testosterone concentrations were higher in the testosterone-exposed-males. While LH response to the GNRH analog was higher in the testosterone-exposed males than in the control males, testosterone responses did not differ between the treatment groups. The testosterone:LH ratio was higher in the control males than in the testosterone-exposed males of 30 weeks of age, suggestive of reduced Leydig cell sensitivity to LH in the testosterone-exposed males. The expression of LHR mRNA was lower in the testosterone-exposed males, but the mRNA expression of steroidogenic enzymes did not differ between the groups. These findings indicate that prenatal testosterone excess has opposing effects at the pituitary and testicular levels, namely increased pituitary sensitivity to GNRH at the level of pituitary and decreased sensitivity of the testes to LH.