Ovine fetal testis stage-specific sensitivity to environmental chemical mixtures

Exposure of the fetal testis to numerous individual environmental chemicals is frequently associated with dysregulated development, leading to impaired adult reproductive competence. However, ‘real-life’ exposure involves complex mixtures of environmental chemicals (ECs). Here we test the consequences, for the male fetus, of exposing pregnant ewes to EC mixtures derived from pastures treated with biosolids fertiliser (processed human sewage). Fetal testes from continuously exposed ewes were either unaffected at Day 80 or exhibited a reduced area of testis immunostained for CYP17A1 protein at Day 140. Fetal testes from Day 140 pregnant ewes exposed transiently for 80 day periods during early (0-80 days), mid (30-110 days) or late (60-140 days) pregnancy, had fewer Sertoli cells and reduced testicular area stained for CYP17A1. Male fetuses from ewes exposed during late pregnancy also exhibited reduced fetal body, adrenal and testis mass, anogenital distance and lowered testosterone: collectively indicative of an anti-androgenic effect. Exposure limited to early gestation induced more testis transcriptome changes than observed for continuously exposed Day 140 fetuses. These data suggest that a short period of EC exposure does not allow sufficient time for the testis to adapt. Consequently, testicular transcriptomic changes induced during the first 80 days of gestation may equate with phenotypic effects observed at Day 140. In contrast, relatively fewer changes in the testis transcriptome in fetuses exposed continuously to ECs throughout gestation is associated with less severe consequences. Unless corrected by or during puberty, these differential effects would predictably have adverse outcomes for adult testicular function and fertility.

SELECTIVE ANDROGEN RECEPTOR MODULATORS (SARM) – A NEW TEMPTATION IN SPORTS. TYPES, MODE OF ACTION AND SIDE EFFECTS OF THEIR APPLICATION: REVIEW

ABSTRACT The selective androgen receptor modulators (SARMs) are androgen receptor ligands that bind to androgen receptors on target cells and exhibit a more pronounced anabolic effect at the expense of the androgenic effect on the latter. The aim of the article is to explain what SARMs are and how they are connected with sports. We used over 300 articles for the last 20 years connected with SARMs. Recently, the interest in these new molecules and their use has grown significantly, including in sports, which has led to their listing on the WADA prohibited list. In recent years, a lot of data have been gathered, both on the mechanism of action of a number of steroidal and non-steroidal representatives of this class of substances and on the adverse side effects of their use, as the latter should be well-known to sports doctors and especially to amateurs practicing in their free time and willing to increase their muscle mass with a view to preventing any potential health risks.

Composition of Royal Jelly (RJ) and Its Anti-Androgenic Effect on Reproductive Parameters in a Polycystic Ovarian Syndrome (PCOS) Animal Model

Royal jelly (RJ) has been shown to contribute its positive effects upon imbalance in the reproductive system. However, it remains unknown as to whether RJ has an anti-androgenic effect on reproductive parameters in a polycystic ovarian syndrome (PCOS) animal model. Composition of RJ was assessed by phytochemical screening and the LC–MS method. Forty immature female rats (3 weeks, 40–50 g) were randomly divided into five groups (n = 8 per group), i.e., control, testosterone (T), T+100RJ (100 mg/kg/day), T+200RJ (200 mg/kg/day RJ), and T+400RJ (400 mg/kg/day RJ) groups. Hyperandrogenism was induced by daily subcutaneous injection of T propionate for 3 weeks, followed by oral RJ for 4 weeks. The T+200RJ group had a significantly higher follicle-stimulating hormone level, and significantly lower luteinizing hormone, testosterone, and estradiol levels in comparison to the T group. Malondialdehyde level and glutathione peroxidase activity were significantly lower, while total antioxidant capacity level was significantly higher in the T+200RJ group compared to the T group. Histologically, the T+200RJ group showed recovery of various stages of ovarian follicular development. RJ at 200 mg/kg/day for 4 weeks significantly improved reproductive parameters in PCOS rats partly due to its anti-androgenic effect through antioxidant action and probably due to modulation on estrogenic activity, which needs further study to evaluate its exact mechanism of action.

Risk Assessment of the Plant Protection Product PROMAN – with the Active Ingredient Metobromuron

Proman is a new product containing the active substance metobromuron. The intended use is as a broad spectrum selective herbicide for potatoes grown outdoors. VKM’s Panel on Plant Protection Products has discussed the questions raised by The Norwegian Food Safety Authority in the Terms of reference and has stated the following opinion: On the relevance of the carcinogenic effects observed in the rat carcinogenicity study; fibrosarcomas in females and pheochromocytomas and Leydig cell tumours in males: It is the opinion of VKM’s Panel for Plant Protection Products that the relevance of the observed incidence in mammary gland tumours and Leydig cell tumours in the rat carcinogenicity study is strengthened by the fact that the tumours are observed in hormone responsive tissues. The panel concludes that the carcinogenic effects observed in the rat carcinogenicity study are likely to be relevant for tumours that are influenced by the endocrine system, also in humans. On the higher incidences of still dumbbell-shaped centres of thoracic vertebrae and nonossification of the 13th rib observed in the rat developmental toxicity study and whether these are considered to be malformations: VKM’s Panel on Plant Protection Products has discussed the classification of the different types of incomplete ossifications and concluded that incomplete ossification of sternebrae and non-ossification of the 13th rib in rats should by itself be considered to be variations, and not adverse developmental effects. On the other hand, the Panel agrees with ECHA that the “thoracic vertebral centres still dumbbell-shaped” should be considered as malformations, due to limited data and understanding of the mechanism underlying the observed slow reversal of these anomalies. Furthermore, it is the view of the Panel that the different types of retarded ossification induced by the exposure of metobromuron should be considered as a whole when assessing for developmental effects. On the establishment of the NOAEL for the developmental toxicity study in rats and the reference value (ARfD): VKM’s Panel on Plant Protection Products supports the proposal of an ADI value of 0.008 mg/kg bw/day based on a NOAEL of 0.8 mg/kg bw/day from the 2-year study in mouse, and VKM Report 2015: 03 5. AOEL of 0.016 mg/kg bw/day based on the NOAEL of 1.6 mg/kg bw/day from the 1-year feeding study in dog. An UF of 100 is applied. The panel suggests on the other hand an ARfD of 0.03 mg/kg bw based on a LOAEL of 10 mg/kg bw /day with the observations of incomplete ossification in the rat developmental study. An UF of 300 is applied. On the possible anti-androgenic potential of metobromuron: It is the view of the Panel that the rat carcinogenicity study suggests that metobromuron may possess endocrine disrupting potency. The data from the Hershberger in vivo rat study and the in vitro studies is also suggestive of a weak anti-androgenic effect. Thus, it is the opinion of the VKM Panel on Plant Protection Products that an anti-androgenic effect of metobromuron cannot be excluded.

Androgenic Effect and Phytochimie of the Bark of Trunk of Buchholzia coriacea Engl. (Capparidaceae)

The testosterone is the main androgen produced by the testes among the males. Her absence is responsible for erectile dysfunction and the loss of the sexual performance. The aim of the present study is to evaluate the androgenic effect and to determine the profile phytochemestry of the barks of trunk of B. coriacea. Fifteen days after the castration, the animals left in group and, received the aqueous extract of B. coriacea (100, 250 and 500 mg/kg, p.o). The sexual parameters (mounts sexual, number of erections, number of ejaculations and the time of latency) have been valued, and compared, to the witnesses groups: water distilled (0,5 ml/100 mg, p.o) and Enanthate of testosterone (1 mg/mL, i.m). The dosage of the testosterone has been achieved by the technic of ELYSA analysis. The determination of the chemical families has been achieved by the technique of coloration in tubes. The aqueous extract of B. coriacea (100,250 and 500 mg/kg, p.o) has an effect androgenic because managed daily during 15 days, it provokes an increase of the rate plasmatic of the testosterone and the bodily weight of the rats, maintains the sexual parameters among the castrated rat, extract the number of ejaculations. The barks of trunk of B. coriacea would contain the stérols, the flavonoides, the saponosids that could be responsible for the sexual effects and androgénic observed. The aqueous extract of the plant would possess the properties androgenic would be to advise the patients presenting problems of masculine barrenness. Keywords: Androgen - Phytochimie - Buchholzia - coriacea

Masculinization of featherfin squeaker Synodontis eupterus Boulenger, 1901 larvae using javanese long pepper extract Piper retrofractum and increased rearing temperature

Javanese long pepper (Piper retrofractum) is known to have androgenic effect, could act as phytosteroid and alternative to masculinization. This research aimed to evaluate the optimum dose of the Javanese long pepper extracts combined with increased rearing temperature on featherfin squeaker masculinization through larva immersion. This research was designed using a completely randomized design with 8 treatments consisted of Javanese long pepper extract doses of 0.0625 mg L-1and 0.125 mg L-1, negative control (without both extract and 17α-metiltestosterone) and positive control (2 mg L-117α-metiltestosterone). Each of them consisted of two different temperature treatments, namely, normal (26-27ᴼC) and 32ᴼC. After five hours treatment, larvae were reared until five months age. The fish age four and then five months were dissected and their gonads were taken for acetocarmine and histology preparation. Beside that the percentage of fish survival, body length, weight gain, and specific growth rate were also recorded in certain period. The result showed that the Javanese long pepper extract dose at 0.125 mg L-1 with normal temperature treatment produced the highest male ratio and significantly different compare with control. Giving this dose to larvae did not affect fish survival and growth, meanwhile increased temperature treatment could not increase the effectivity of Javanese long pepper extract.