Multigenerational reproductive assessment of 4-methylimidazole administered in the diet to Hsd:Sprague Dawley SD rats

The general population, including children and adolescents, is exposed to 4-methylimidazole (4-MI) in the diet. 4-MI is a by-product of caramel color manufacturing. It has been previously classified as a possible human carcinogen and displays potential reproductive toxicity. A follow up assessment of reproductive toxicity was conducted in rats utilizing the reproductive assessment by continuous breeding paradigm, in which multiple generations were exposed to 4-MI in diet at 750, 2500, and 5000 ppm. 4-MI exposure was associated with delays in preputial separation and vaginal opening, impairment in reproductive performance, and concomitant histopathological findings in the prostate, testis, and epididymis at 2500 and 5000 ppm. The Lowest Observed Adverse Effect Level for reproductive (based on prostate atrophy) and developmental toxicity (based on delays in preputial separation and vaginal opening) was 750 ppm, equivalent to approximately 50−60 mg/kg bw/day.     

染色体多态性在生殖异常方面的临床效应

染色体多态性是染色体异染色质区域一种微小而恒定的变异,包括结构、带纹宽窄、着色强度等方面的变异,常发生于1、9、16号染色体,D、G组染色体,以及Y染色体。近年来,染色体多态性与生殖方面的关系日益受到人们的关注,本文将近期国内外相关研究综述如下。     

长链非编码RNA THOR在生殖与肿瘤中调控的研究现状

睾丸相关的高度保守的致癌性lncRNA(Testis-associated Highly-conserved Oncogenic long non-coding RNA,THOR)是一类非编码RNA,在哺乳动物睾丸及肿瘤组织中特异性表达,参与雄性生殖过程,调控肿瘤细胞的发生发展。本文对lnc-THOR在生殖和肿瘤中的研究进展进行综述,为雄性生殖有关疾病和肿瘤的表观遗传机制研究提供新的见解,并为其寻找潜在的治疗靶点。     

Reversibility of dopamine receptor antagonist-induced hyperprolactinemia and associated histological changes in Tg RasH2 wild-type mice

The purpose of this study was to better understand the biological effects of increased prolactin levels induced in mice by dopamine D₂ receptor antagonist molindone treatment. Toxicokinetics, prolactin levels, and reproductive tissue histology were evaluated in Tg rasH2 wild-type mice treated orally with molindone at 0, 5, 15, and 50 mg/kg/day for 6 months, followed by a 2-month posttreatment recovery period. A greater than dose-proportional increase in molindone exposure ([AUC]_0 ‒ 24) was observed on Day 180 for both sexes. Statistically significant (P < 0.01) increases in prolactin levels were observed in most treatment groups compared with controls at 0.5 h postdose on Days 1 and 180. Prolactin levels returned to baseline levels during the recovery period. Microscopic changes attributable to hyperprolactinemia, including corpora lutea enlargement and interstitial cell atrophy in the ovaries, and atrophy of the uterus and vagina were observed on Day 180. These changes were reversed during the recovery period in the 5- and 15-mg/kg/day treatment groups. Mice receiving molindone at 50 mg/kg/day also showed signs of reversal on histologic examination.     

In utero exposure to the endocrine disruptor di(2-ethylhexyl) phthalate targets ovarian theca cells and steroidogenesis in the adult female rat

Di-2-ethylhexyl phthalate (DEHP) is an endocrine disruptor used in industry as an additive to polyvinyl chloride-based products. Pregnant dams were gavaged with oil, 1, 20, 50, or 300 mg of DEHP/kg/day from gestational day 14 until birth in order to characterize the effects of DEHP in the adult female offspring. In utero exposure to DEHP resulted in reduced estrogen levels at proestrus. Theca cell layer thickness was decreased starting at 50 mg DEHP/kg/day dose. Follicle-stimulating hormone levels were significantly increased at proestrus and estrus. F1 reproduction using a known breeder was not affected. F3 generation showed a decreased pregnancy rate and weight, and increased litter size in the animals exposed to 20 mg DEHP/kg/day. The data presented herein suggest that in utero exposure to DEHP targets the theca cell layer and decreases the estrus cycle steroid surge, but despite these effects, does not cause infertility.     

The effects of long-term testosterone,gonadotropin-releasing hormone agonist and pimozide treatments on testicular development and luteinizing hormone levels in juvenile and early maturing striped bass,Morone saxatilis

The present study was conducted to test the responsiveness of the juvenile male reproductive axis to hormonal stimulation and to compare it to that of early maturing males. Long-term treatments with various combinations of T, GnRHa and pimozide did not result in an increased incidence of early maturing males, but did stimulate spermatogenesis slightly in juvenile fish. In early maturing males, the treatments appeared to be inhibitory since they resulted in a reduction of the GSI and a lower incidence of spermiating males. In early maturing males, pituitary LH content was elevated by GnRHa treatments alone while in juvenile males a combination of T and GnRHa was needed to increase the levels of LH in the pituitary. Thus, T may play an important role during puberty by potentiating the effects of GnRH on LH synthesis. In both juvenile and early maturing males, plasma LH levels could be increased only by high doses of GnRHa (in combination with T). Therefore, LH synthesis and release probably require different levels of GnRH stimulation. A GnRH challenge (single injection of 50 microg GnRHa/kg) at the end of the experiment resulted in a dramatic elevation of plasma LH levels in almost all animals. This finding demonstrates that pituitaries from juvenile and early maturing males were responsive to GnRHa stimulation, even after long-term hormonal treatments. The addition of pimozide did not affect the T- and GnRHa-induced increase in pituitary LH content but inhibited the release of LH in response to a GnRHa challenge. In conclusion, high doses of GnRHa in combination with T can increase plasma LH levels in juvenile males but do not induce complete testicular maturation. Factors other than T, GnRHa or LH are probably involved in the induction and completion of spermatogenesis.     

钉螺在巢湖生存繁殖的模拟试验

目的探讨钉螺在巢湖生存繁殖的可能性。方法在巢湖湖区马尾河口划定一区域,模拟巢湖环境为试验区;在血吸虫病流行区无为县姚沟镇划定一区域,模拟血吸虫病流行区环境为对照区,开展现场模拟环境钉螺生存繁殖试验。同时收集巢湖流域生态环境资料。结果巢湖流域气象条件适合钉螺生存繁殖;2007年6-12月,试验区和对照区钉螺存活率差异无统计学意义（P均〉0.05）;2007年7-12月,在试验区和对照区均捡获子代钉螺;研究期间试验区和对照区土壤湿度差异无统计学意义（U=10.00,P=0.073）。结论钉螺能够在模拟巢湖环境中生存繁殖。今后应加强对巢湖潜在钉螺孳生环境的监测,以防钉螺向湖区扩散。     

Ten new cases of Balanced Reciprocal Translocation Mosaicism (BRTM): Reproductive implications,frequency and mechanism

Chromosomal anomalies are well known to be an important cause of infertility, sterility and pregnancy loss. Balanced Reciprocal Translocation Mosaicism (BRTM) is an extremely rare phenomenon, mainly observed in subjects with a normal phenotype accompanied by reproductive failure. To date the mechanism of origin and the incidence of BRTM are poorly defined.Here we describe 10 new cases of BRTM. In 9 cases chromosome analysis revealed the presence of two different cell lines, one with a normal karyotype and the second with an apparently balanced reciprocal translocation. In the remaining case, both cell lines showed two different, but apparently balanced, reciprocal translocations.We document the clinical implications of BRTM, discuss its frequency in our referred population and suggest that carrier individuals might be more frequent than expected.