Research collaborations in Tajikistan: lessons to be learnt.

We have been working on an association of physicians 'links with developing countries' scheme in Tajikistan, which is a nation of 7.5 million people, 93% of which is mountainous, of a similar size to England and Wales, landlocked, resource-poor and richly licked by the brush of history. Understanding the challenges faced by academics working with Tajikistan today requires a cursory understanding of Tajikistan's genesis. Through this lens, present-day technical, organizational and socio-political challenges can be appropriately considered, with a view to improving academic collaboration in the future.

An in vivo and in vitro investigation into the effects of alpha- chlorohydrin on sperm motility and correlation with fertility in the Han Wistar rat.

Following a recommendation from the International Conference on Harmonisation, pharmaceutical companies are now monitoring possible drug effects on sperm motility in the rat during preclinical safety studies by assessing sperm motility (velocity). However, it is not known precisely how changes in sperm motility relate to fertility. Therefore, the effects of alpha-chlorohydrin on sperm motility were investigated and related to fertility both in vivo and in vitro. alpha-Chlorohydrin was given orally to male rats using a range of doses: 0, 5, 10, and 20 mg/kg for at least 5 consecutive days. Sperm were than assessed for motility using a standard scoring system (operators' observation of sperm) that graded degree of motility (i.e., 0 = i mmotile to 4 = very motile). The results showed a dose-related decrease in sperm motility. The sperm also appeared to move with a "jerky" action. Surprisingly, when this was correlated to fertility, none of the females mated with treated males became pregnant. A dose-related decrease in pregnancy would perhaps have been expected. There was no effect on sperm morphology, and testicular and epididymal pathology were only seen after doses of 20 mg/kg. When sperm from untreated rats were incubated with alpha-chlorohydrin in vitro at concentrations of 0, 0.5, 1.0, and 1.5 mM, sperm motility and motion were similarly affected as observed in vivo. However, the fertilization capacity (in vitro fertilization) of the treated sperm showed a concentration-related reduction in percentage fertilization, and there was also evidence of abnormal embryo development. These findings suggest that the present standard scoring system used in preclinical safety studies is not a comprehensive indicator of sperm function and/or fertility. A better understanding of sperm movement, therefore, is desirable so effects on sperm motility can be related to fertility.

Establishing the timing of implantation in the Harlan Porcellus Dutch and New Zealand White rabbit and the Han Wistar rat.

The purpose of this study was to establish the timing of the onset of implantation in both the Harlan Porcellus Dutch and New Zealand White rabbit and the Han Wistar rat. Implantation was initiated on Day 5 (rat) and 7 (rabbit) and established by Day 7 and 8 of gestation in the rat and rabbit, respectively. Recent guidelines on toxicity testing during embryo-fetal development studies require that maternal exposure to pharmaceutical compounds does not occur until after implantation has taken place. In order to ensure that this is the case, female Harlan Porcellus Dutch and New Zealand White rabbits and Han Wistar rats were sacrificed on different days of gestation, over the expected periods of implantation. The presence of preimplantation blastocysts in the uterus was investigated, and evidence of established implantation sites was assessed.

The influence of phthalate esters on Leydig cell structure and function in vitro and in vivo.

Phthalate esters are widely used in the manufacture of plastics and have been shown to cause testicular toxicity, purportedly, by targeting the Sertoli cell alone. Recent evidence, however, indicates that a paracrine control exists between Sertoli and Leydig cells and the breakdown of one component of this relationship is therefore detrimental to normal function. However, no data that explore the influence of testicular toxins on Leydig cell structure and function have been published hitherto. The preliminary studies reported here were initiated to test the hypothesis that phthalate intoxication may adversely alter Leydig cell structural and functional integrity. Four phthalate esters, namely, di(2-ethylhexyl) phthalate (DEHP, di-n-pentyl phthalate (DPP)., di-n-octyl phthalate (DOP), and diethyl phthalate (DEP) were investigated in vivo and their monoesters (MEHP, MPP, MOP, and MEP, respectively) in vitro for indications of Leydig cell toxicity in the rat. Rats were dosed by oral gavage with 2 g phthalate diester/kg/day in corn oil vehicle for 2 days, while Leydig cell primary cultures were incubated with 1,000 microM monoester for 2 hr. Light and electron microscopy were undertaken to determine the type and degree of any changes. Phthalate esters exerted a direct effect on Leydig cell structure and function (as determined by testosterone output) with correlation of the in vitro and in vivo effects of MEHP (DEHP) and MOP (DOP). No effects on Leydig cell structure or function were seen with MPP (DPP), although Sertoli cell cytoplasmic rarefaction and vacuolation were observed in vivo. DEP produced Leydig cell ultrastructural alterations in vivo. We conclude that individual phthalate esters may exert effects on both Sertoli and Leydig cells or one cell type alone.