Chronic exposure to the fungicide propiconazole: Behavioral and reproductive evaluation of F1 and F2 generations of male rats.

Several studies have suggested that propiconazole (PROP) may be an endocrine disruptor; possibly altering the activity of the CYP51 enzyme, which is part of the cholesterol biosynthesis pathway required for the production of sexual steroid hormones. Another PROP effect is inhibition of the aromatase enzyme that converts androgens into estrogens, which could lead to negative effects on reproductive parameters. Therefore, the present study evaluated the reproductive and developmental toxicity of PROP by exposing two generations (F1 and F2) of male rats to this fungicide, since a previous study from our lab reported that PROP has anti-estrogenic and anti-androgenic activities (Costa et al., 2015) in the male parental (P) generation. The F1 males were exposed to PROP (4 or 20mg/kg) through germ cells (via the P generation), intra uterus, and lactation, following treatment by gavage from post-natal day (PND) 21 to 120, while the F2 generation was exposed through germ cells, intra uterus, and lactation. The parameters observed in both F1 and F2 generations were: body weight, anogenital distance (PND 0 and 21), ontogenic reflex, testosterone plasmatic levels, testis weight, and testicular histomorphology (PND 21); and in the F1 generation only: preputial separation (PND 40), sexual behavior, organ weights, testosterone and estradiol plasmatic levels (PND 120), sperm count and morphology, and testicular histomorphology at adulthood. In the F1 and F2 generations, PROP (4mg/kg) presented a decrease in testosterone levels, and in the F1 decreases in the vas deferens weight, without hormonal and functional changes of the reproductive organs, either at 4mg/kg or at 20mg/kg, in adulthood. Based on the results of this work, PROP did not alter the gonadal-endocrine parameters under these exposure conditions in rats.

Reproductive parameters of female Wistar rats treated with methylphenidate during development.

Methylphenidate (MPH), a psychoactive agent that acts mainly by blocking the uptake of dopamine, is the main drug used to treat Attention Deficit Hyperactivity Disorder in children and adolescents. During development, important changes in brain architecture and plasticity occur, these changes, sensitive to exposure to stimulant drugs, are important in the control of GnRH secretion, influencing the release of sex hormones throughout the ovarian cycle. This study investigated the effects of repeated treatment with MPH during development on reproductive parameters of adult female rats. Wistar rats received MPH 2.5mg/kg, MPH 5.0mg/kg, or tap water (gavage) from postnatal day (PND) 21 to PND 60. From PND 75, one subgroup of females was selected for evaluation of estrous cycle, estradiol levels, weight of sexual organs, and histomorphological analysis of ovary follicles and uterus. In another subgroup, the sexual and maternal behaviors were evaluated at PND 90 and on lactational day 5, respectively. No significant alterations were observed in the MPH groups. This study demonstrated that repeated administration of MPH during the period corresponding to childhood to early adulthood does not interfere in the reproductive function of female rats in adulthood.

Orchidopexy restores morphometric-stereologic changes in the caput epididymis and daily sperm production in cryptorchidic mice, although sperm transit time and fertility parameters remain impaired.

OBJECTIVE: To evaluate the changes in the caput epididymis following cryptorchidism and orchidopexy. DESIGN: Experimental study in a research laboratory. SETTING: Reproductive biology research laboratory. ANIMAL(S): Immature male and mature female mice (C57BL/6). INTERVENTION(S): Experimental cryptorchidism and orchidopexy. MAIN OUTCOME MEASURE(S): Morphometric-stereologic analyses, serum testosterone dosage, immunohistochemical staining of the antigen TRA54 (testicular germ cells immunized to a rat monoclonal antibody), smooth muscle α-actin (SM α-actin) and SM myosin heavy chain, sperm transit time, and fertility parameters. RESULT(S): There was a significant reduction in the morphometric-stereologic parameters in the cryptorchidic mice. These parameters demonstrated significant recovery following orchidopexy. Staining for an androgen-dependent antigen, TRA54, was observed in all groups. SM α-actin and SM myosin heavy chain staining was significantly increased in the cryptorchidism group but stable in the orchidopexy group. Despite the recovery of daily sperm production in the testes, the sperm transit time in the epididymis and fertility parameters remained significantly reduced in the orchidopexy group. CONCLUSION(S): In cryptorchidic animals, there was an acceleration of sperm passage through the epididymal duct. Orchidopexy did not restore the normal passage time. Accordingly, there was a significant reduction in the fertility parameters in the cryptorchidic group that were not fully recovered following orchidopexy.

Nandrolone decanoate and physical effort: histological and morphometrical assessment in adult rat uterus.

In the past decades, the therapeutic use of anabolic androgenic steroids (AAS) has been overshadowed by illicit abuse of these drugs by athletes and non-athletes. Since that AAS can affect the reproductive tract, resulting in reproduction and fertilization damages, the purpose of this study was to investigate the nandrolone decanoate (ND) effects, associated or not with physical effort, on the uterine histomorphometric parameters. Female Wistar rats, sedentary or not, were exposed to treatment with ND by intraperitoneal injection (5 mg/kg/day, once a week) during four consecutive weeks. Control animals, sedentary or not, received vehicle alone (propylene glycol) in the same manner. The physical activity was forced swimming (20 min/day). During the experiment, all animals were monitored by daily vaginal smears. After 30 days of treatment, the females were sacrificed and their uteri collected and examined under light microscopy techniques. The ND-treated females showed estrus acyclicity and decreased thickness of both the epithelium and endometrial stroma. A reduction in the number and size of blood vessels was also found in ND-treated rats submitted to physical effort when compared to ND sedentary rats. ND-treated rats, regardless of exercise, exhibited stromal fibrosis and reduced gland ducts that displayed high mitotic activity. A remarkable widespread presence of leukocytes occurred in rats receiving ND and submitted to exercise. These results suggest that ND associated or not with physical effort causes histomorphometric changes to the rat uterus.

Ovarian histology and follicular score in female rats treated with nandrolone decanoate and submitted to physical effort.

The study was conducted to analyze the histology of the ovaries of adults rats treated with steroids, and submitted or not to physical effort. The control group consisted of females submitted to physical effort and sedentary females, both of which received a physiological solution of 0.9% saline. Treated females, sedentary or not, received 6 mg/kg of body weight of nandrolone decanoate. The steroid and physiological solution were administered intraperitoneally, with a single injection per week for 4 consecutive weeks. The applied physical effort was swimming (20 minutes daily, 5 days/week, for the 4 weeks of treatment). Serial sections (5 mum) of ovaries were prepared for histological evaluation and follicular score. The weight of ovaries and hypophysis, the number of antral and atretic follicles, and the area of corpus luteum were all affected by the steroids. In the ovaries of the control groups, well-developed corpus luteum was observed. In the treated groups, the cortical stroma was occupied by ovarian interstitial tissue. The females treated with steroids presented estral acyclicity. The use of nandrolone decanoate, whether associated with physical effort or not, affected the morphological pattern of the ovaries.