Protective effect of Nigella sativa oil against acetamiprid induced reproductive toxicity in male rats.

The present study was designed to investigate the adverse reproductive effects of acetamiprid, besides the possible protective role of Nigella sativa oil (NSO), as a potential antioxidant agent. Thirty-two male Wistar rats were allocated into four equal groups of eight, control (CRL), acetamiprid (ACMP, 27 mg/kg), Nigella sativa oil (NSO, 0.5 ml/kg) and in combination (ACMP + NSO). The experimental animals were dosed by gavage (5 days per week) for 45 consecutive days. Body weight gain, reproductive organs weights, sperm characteristics, testosterone, and thiobarbutiric acid-reactive substances (TBARS) levels were investigated. The obtained results showed that ACMP decreased significantly (p < 0.001) the body weight gain and the absolute weights of reproductive organs (testes, epididymis, and seminal vesicles). Furthermore, significant alterations at least (p < 0.01) in semen characteristics were noted in ACMP group as evidenced by a decline in spermatids number, sperm count, sperm motility, and testosterone level with an increase in abnormal and dead sperm and TBARS level. Treatment with NSO alone may stimulate spermatogenesis, increased significantly (p < 0.001) spermatids number and the weight of seminal vesicles. On the other hand, the co-administration of NSO along with ACMP can mitigate more efficiently and modulate in certain cases the adverse effects induced by ACMP on reproductive organs weights, semen quality, testosterone, and TBARS levels (at least p < 0.001). This obvious protective role of NSO against ACMP induced reproductive toxicity may be due to its antioxidant properties and ability to reduce TBARS levels as shown in this work.

Long nuclear-retained non-coding RNAs and allele-specific higher-order chromatin organization at imprinted snoRNA gene arrays.

The imprinted Snurf-Snrpn domain, also referred to as the Prader-Willi syndrome region, contains two approximately 100-200 kb arrays of repeated small nucleolar (sno)RNAs processed from introns of long, paternally expressed non-protein-coding RNAs whose biogenesis and functions are poorly understood. We provide evidence that C/D snoRNAs do not derive from a single transcript as previously envisaged, but rather from (at least) two independent transcription units. We show that spliced snoRNA host-gene transcripts accumulate near their transcription sites as structurally constrained RNA species that are prevented from diffusing, as well as multiple stable nucleoplasmic RNA foci dispersed in the entire nucleus but not in the nucleolus. Chromatin structure at these repeated arrays displays an outstanding parent-of-origin-specific higher-order organization: the transcriptionally active allele is revealed as extended DNA FISH signals whereas the genetically identical, silent allele is visualized as singlet DNA FISH signals. A similar allele-specific chromatin organization is documented for snoRNA gene arrays at the imprinted Dlk1-Dio3 domain. Our findings have repercussions for understanding the spatial organization of gene expression and the intra-nuclear fate of non-coding RNAs in the context of nuclear architecture.

Chronic crude garlic-feeding modified adult male rat testicular markers: mechanisms of action.

BACKGROUND: Garlic or Allium sativum (As) shows therapeutic effects such as reduction of blood pressure or hypercholesterolemia but side-effects on reproductive functions remain poorly investigated. Because of garlic's chemical complexity, the processing methods and yield in preparations differ in efficacy and safety. In this context, we clarify the mechanisms of action of crushed crude garlic on testicular markers. METHODS: During one month of treatment, 24 male rats were fed 5%, 10% and 15% crude garlic. RESULTS: We showed that crude garlic-feeding induced apoptosis in testicular germ cells (spermatocytes and spermatids). This cell death process was characterized by increased levels of active CASP3 but not CASP6. Expression of the caspase inhibitors BIRC3 and BIRC2 was increased at all doses of As while expression of XIAP and BIRC5 was unchanged. Moreover, expression of the IAP inhibitor DIABLO was increased at doses 10% and 15% of As. The germ cell death process induced by As might be related to a decrease in testosterone production because of the reduced expression of steroidogenic enzymes (Star, Cyp11a, Hsd3b5 and Hsd17b). Evaluation of Sertoli markers showed that TUBB3 and GSTA2 expression was unchanged. In contrast, AMH, RHOX5 and CDKN1B expression was decreased while GATA4 expression was increased. CONCLUSION: In summary, we showed that feeding with crude garlic inhibited Leydig steroidogenic enzyme expression and Sertoli cell markers. These alterations might induce apoptosis in testicular germ cells.

Retinoid signaling during spermatogenesis as revealed by genetic and metabolic manipulations of retinoic acid receptor alpha.

The importance of dietary retinol (vitamin A) and retinoid signaling for normal development and differentiation has been recognised for many years. Vitamin A deficiency results in a variety of abnormalities, most of which can be corrected by supplementing the diet with all-trans-retinoic acid (ATRA), with the exception of blindness and male sterility. ATRA, an active metabolite of vitamin A, functions primarily by binding to nuclear receptors of the steroid hormone superfamily, the retinoic acid receptors (RARs). Gene targeting studies revealed the importance of ATRA signaling through the RARs for spermatogenesis. Mice that are homozygous for a null mutation in the gene encoding RARalpha, Rara-/-, exhibit defects in spermatogenesis and male sterility. The abnormalities in these RARalpha-deficient testes have been examined in detail in a series of recent studies from our laboratory and will be summarised in this paper. We also review how dietary, pharmacologic and genetic strategies, alone or in combination, can be used to gain further insight into retinoid function in mammalian spermatogenesis.