The progression of spermatogenesis in the developing rat testis followed by ³¹P MR spectroscopy

To evaluate the use of human testicular 31P MR spectroscopy as a diagnostic tool to differentiate between several stages of male infertility, we have studied the testicular levels of several phosphorus containing compounds in the rat in relation to the condition of spermatogenesis and the cell types present in the seminiferous tubules of the testis. During testicular maturation several characteristic changes occur in the 31P MR spectrum of the testis of male Wistar rats. The phosphomonoester/adenosine triphosphate (PM/ATP) ratio shows a decline from 1.61 to 1.02 between the age of 3 and 12 weeks, whereas the phosphodiester (PD)/ATP ratio increases from 0 to 0.72. The testicular pH increases in the same time from 7.06 to 7.32. Testicular MR data obtained after 12 weeks of age onward do not show significant change anymore. The high PM/ATP ratio is associated by a relative high amount of proliferating spermatogonia and spermatocytes during meiosis in the testis, whereas the PD peak seems to be correlated with the release and maintenance of spermatozoa. The MR spectra show a specific fingerprint in all developmental stages of the rat testis as a result of the different cell types in the testis. © 1992 Academic Press, Inc.</p

Modulation of Serotonin Transporter Function during Fetal Development Causes Dilated Heart Cardiomyopathy and Lifelong Behavioral Abnormalities

BACKGROUND: Women are at great risk for mood and anxiety disorders during their childbearing years and may become pregnant while taking antidepressant drugs. In the treatment of depression and anxiety disorders, selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed drugs, while it is largely unknown whether this medication affects the development of the central nervous system of the fetus. The possible effects are the product of placental transfer efficiency, time of administration and dose of the respective SSRI. METHODOLOGY/PRINCIPAL FINDINGS: In order to attain this information we have setup a study in which these parameters were measured and the consequences in terms of physiology and behavior are mapped. The placental transfer of fluoxetine and fluvoxamine, two commonly used SSRIs, was similar between mouse and human, indicating that the fetal exposure of these SSRIs in mice is comparable with the human situation. Fluvoxamine displayed a relatively low placental transfer, while fluoxetine showed a relatively high placental transfer. Using clinical doses of fluoxetine the mortality of the offspring increased dramatically, whereas the mortality was unaffected after fluvoxamine exposure. The majority of the fluoxetine-exposed offspring died postnatally of severe heart failure caused by dilated cardiomyopathy. Molecular analysis of fluoxetine-exposed offspring showed long-term alterations in serotonin transporter levels in the raphe nucleus. Furthermore, prenatal fluoxetine exposure resulted in depressive- and anxiety-related behavior in adult mice. In contrast, fluvoxamine-exposed mice did not show alterations in behavior and serotonin transporter levels. Decreasing the dose of fluoxetine resulted in higher survival rates and less dramatic effects on the long-term behavior in the offspring. CONCLUSIONS: These results indicate that prenatal fluoxetine exposure affects fetal development, resulting in cardiomyopathy and a higher vulnerability to affective disorders in a dose-dependent manner

23Na chemical shift imaging and Gd enhancement of myocardial edema

Myocardial edema can arise in several disease states. MRI contrast agent can accumulate in edematous tissue, which complicates differential diagnosis with contrast-enhanced (CE)-MRI and might lead to overestimation of infarct size. Sodium Chemical Shift Imaging ((23)Na-CSI) may provide an alternative for edema imaging. We have developed a non-infarct, isolated rat heart model with two levels of edema, which was studied with (23)Na-CSI and CE-MRI. In edematous, but viable tissue the extracellular sodium (Na (e) (+)) signal is hypothesized to increase, but not the intracellular sodium (Na (i) (+)) signal. Isolated hearts were perfused at 60 (n = 6) and 140 mmHg (n = 5). Dimethyl methylphosphonate (DMMP) and phenylphosphonate (PPA) were used to follow edema formation by (31)P-MR Spectroscopy. In separate groups, Thulium(III)1,4,7,10 tetraazacyclododecane-N,N',N″,N'''-tetra(methylenephosphonate) (TmDOTP(5-)) and Gadovist were used for (23)Na-CSI (n = 8) and CE-MRI (n = 6), respectively. PPA normalized signal intensity (SI) was higher at 140 versus 60 mmHg, with a ratio of 1.27 ± 0.12 (p <0.05). The (DMMP-PPA)/dry weight ratio, as a marker of intracellular volume, remained unchanged. The mid-heart cross sectional area (CSA) of the left ventricle (LV) was significantly increased at 140 mmHg. In addition, at 140 mmHg, the LV Na (e) (+) SI increased with a 140 mmHg/60 mmHg ratio of 1.24 ± 0.18 (p <0.05). Na (i) (+) SI remained essentially unchanged. With CE-MRI, a subendocardially enhanced CSA was identified, increasing from 0.20 ± 0.02 cm(2) at 60 mmHg to 0.31 ± 0.02 cm(2) at 140 mmHg (p <0.05). Edema shows up in both CE-MRI and Na (e) (+) . High perfusion pressure causes more edema subendocardially than subepicardially. (23)Na-CSI is an attractive alternative for imaging of edema and is a promising tool to discriminate between edema, acute and chronic M