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Biomedical subjects

J S Fisher

Publications and source records attributed to J S Fisher.

At least 19 recordsLinked to original sources
PubMed1999

Stiffness and muscle function with age and reduced muscle use.

Changes in passive muscle stiffness with age and disuse were assessed in male Fischer-344 and Brown Norway rats. Three groups of rats were studied: young (approximately 7 months old), old (approximately 33 months old), and old that had undergone 2 weeks of hindlimb unweighting, a model of reduced muscle use. Four hindlimb muscles were examined: the soleus (postural), plantaris (locomotor), extensor digitorum longus (nonpostural), and peroneus longus (nonpostural). Supramaximal stimuli elicited peak tetanic tensions throughout the available range of motion (amount of muscle elongation before the maximal attainable contractile or tetanic tension is obtained) for each muscle, permitting the creation of length-tension curves. Passive tension (amount encountered at each millimeter of change in muscle length) was also recorded throughout the available range of motion and was unchanged with aging and unchanged or reduced with hindlimb unweighting; muscle stiffness remained unchanged under both conditions. Passive tension, however, accounted for a greater proportion of total tension with age and particularly with hindlimb unweighting. A significant loss in muscle range of motion, resulting in a leftward shift in the length-tension curve, occurred with aging in only the plantaris. Hindlimb unweighting resulted in a marked loss in muscle range for all four muscles studied, suggesting that the remaining muscle force was constrained to a very small arc. Significant declines in muscle mass and peak contractile tension, associated with age and hindlimb unweighting, were observed for all four muscles.

Aging↗
PubMed1999

Effect of neonatal exposure to estrogenic compounds on development of the excurrent ducts of the rat testis through puberty to adulthood.

Neonatal exposure to diethylstilbestrol (DES) can alter the structure of the testicular excurrent ducts in rats. We characterized these changes according to dose and time posttreatment and established whether potent estrogens (ethinyl estradiol), environmental estrogens (genistein, octylphenol, bisphenol A, parabens), and tamoxifen induce such changes. Rats were administered these compounds neonatally and assessed at several time points during (day 10, or day 18 for some treatments) and after (days 18, 25, 35, and 75) the treatment period to detect any changes in testis weight, distension of the rete testis and efferent ducts, epithelial cell height in the efferent ducts, and immunoexpression of the water channel aquaporin-1 (AQP-1). Treatment with DES (10, 1, or 0.1 microg/injection; equivalent to 0.37, 0.037, or 0.0037 mg/kg/day, respectively) induced dose-dependent changes in testis weight and all parameters. These effects were most pronounced at days 18 and 25 and appeared to lessen with time, although some persisted into adulthood. Neonatal treatment with ethinyl estradiol (10 microg/injection; equivalent to 0.37 mg/kg/day) caused changes broadly similar to those induced by 10 mg DES. Administration of tamoxifen (2 mg/kg/day) caused changes at 18 days that were similar to those induced by 1 microg DES. Treatment with genistein (4 mg/kg/day), octylphenol (2 mg/injection; equivalent to 150 mg/kg/day), or bisphenol A (0.5 mg/injection; equivalent to 37 mg/kg/day) caused minor but significant (p<0.05) decreases in epithelial cell height of the efferent ducts at days 18 and/or 25. In animals that were followed through to 35 days and/or adulthood, these changes were no longer obvious; other parameters were either unaffected or were affected only marginally and transiently. Administration of parabens (2 mg/kg/day) had no detectable effect on any parameter at day 18. To establish whether these effects of estrogens were direct or indirect (i.e., resulting from reduced follicle-stimulating hormone/luteinizing hormone secretion), the above end points were assessed in animals in which gonadotropin secretion was suppressed neonatally by administration of a gonadotropin-releasing hormone antagonist. This treatment permanently reduced testis weight, but did not affect any of the other end points, apart from a minor transient reduction in efferent duct epithelial cell height at 18 days. This study suggests that structural and functional (expression of AQP-1) development of the excurrent ducts is susceptible to impairment by neonatal estrogen exposure, probably as a consequence of direct effects. The magnitude and duration of adverse changes induced by treatment with a range of estrogenic compounds was broadly comparable to their estrogenic potencies reported from in vitro assays.

Animals↗
PubMed1999

Clinical trials in general surgical journals: are methods better reported?

BACKGROUND: Reports of clinical trials often lack adequate descriptions of their design and analysis. Thus readers cannot properly assess the strength of the findings and are limited in their ability to draw their own conclusions. A review of 6 surgical journals in 1984 revealed that the frequency of reporting 11 basic elements of design and analysis in clinical trials was only 59%. This study attempted to identify areas that still need improvement. METHODS: Eligible studies published from July 1995 through June 1996 included all reports of comparative clinical trials on human subjects that were prospective and had at least 2 treatment arms. A total of 68 articles published in 6 general surgery journals were reviewed. The frequency that the previously identified 11 basic elements of design and analysis were reported was determined. RESULTS: Seventy-four percent of all items were reported accurately (a 15% increase from the previous study), 4% were reported ambiguously, and 23% were not reported; improvement was seen in every journal. The reporting of eligibility criteria and statistical power improved the most. For 3 items, reporting was still not adequate; 32% of reports provided information about statistical power, 40% about the method of randomization, and 49% about whether the person assessing outcomes was blind to the treatment assignment. CONCLUSIONS: Improvements have been made in reporting surgical clinical trials, but in general methodologic questions poorly answered in the 1980s continue to be answered poorly in the 1990s. Editors of surgical journals are urged to provide authors with guidelines on how to report clinical trial design and analysis.

Clinical Protocols↗
PubMed1998

Immobilization effects on contractile properties of aging rat skeletal muscle.

The effect of four weeks of ankle immobilization on muscle mass and in situ contractile properties of soleus (SOL), plantaris (PLA), and extensor digitorum longus (EDL) of 31- and 37-month-old (mo) Fisher 344/Brown Norway rats was examined. Following contractile tests, muscles were harvested, weighed, and analyzed for fiber type and fiber cross-sectional area. Body weights (g) were similar in both control (CON) groups (31 mo, 578 +/- 20; 37 mo, 553 +/- 26; mean +/- SE) and both immobilized (IM) groups (31 mo, 496 +/- 6; 37 mo, 461 +/- 15). Immobilization-related differences in peak tetanic tension (g) were less in 37 mo than 31 mo rats (age x treatment, p < 0.05) for SOL (31 mo, CON 156 +/- 11, IM 63 +/- 12; 37 mo, CON 70 +/- 6, IM 46 +/- 8), PLA (31 mo, CON 435 +/- 13, IM 239 +/- 40; 37 mo, CON 155 +/- 14, IM 152 +/- 20) and EDL (31 mo, CON 227 +/- 13, IM 139 +/- 17; 37 mo, CON 117 +/- 16, IM 108 +/- 4). Immobilization-related differences in muscle mass (mg) were smaller in 37 mo rats compared to 31 mo animals for SOL (31 mo, 206 +/- 14 vs 129 +/- 8, 37 mo, 148 +/- 5 vs 114 +/- 2, age x treatment p < 0.06) and PLA (31 mo, 409 +/- 14 vs 257 +/- 22, 37 mo, 234 +/- 17 vs 181 +/- 18, age x treatment p < 0.05), but immobilization-related muscle mass differences were similar in both age groups for EDL (31 mo, 178 +/- 7 vs 134 +/- 9; 37 mo, 157 +/- 10 vs 112 +/- 7). There were no immobilization-related changes in fiber type distribution in any of the three muscles studied in either age group. The results suggest that disuse-related change is diminished when superimposed on muscles that have already undergone marked age-related decline.

Aging↗
PubMed1998

Abnormalities in functional development of the Sertoli cells in rats treated neonatally with diethylstilbestrol: a possible role for estrogens in Sertoli cell development.

Diethylstilbestrol (DES) was administered neonatally (Days 2-12; 10 microg on alternate days) to rats, and developmental changes in Sertoli cell function were evaluated at 18, 25, and 35 days of age and compared to those observed in rats administered a GnRH antagonist (GnRHa; Days 2 and 5; 10 mg/kg) or a vehicle (controls). DES and GnRHa treatments resulted in similar reductions in both Sertoli cell numbers (40% for DES, 48% for GnRHa) and suppression of testicular growth at 18 and 25 days, though by 35 days the suppression was more pronounced (p < 0.001) in DES-treated animals. Plasma FSH levels were suppressed markedly at 18 and 25 days, but not at 35 days, in GnRHa-treated rats, whereas in DES-treated rats the FSH levels were suppressed significantly only at 35 days. Both treatments suppressed plasma levels of inhibin B, though this was more pronounced (p < 0.05) in DES- than in GnRHa-treated rats. In controls, Sertoli cell immunoexpression of inhibin alpha, sulfated glycoprotein-1 (SGP-1), and androgen receptor (AR) increased in intensity and changed to an adult, stage-dependent pattern by 25 days. In GnRHa-treated rats these changes were reduced in intensity but were similar to those in controls at 35 days. In DES-treated rats, the increase in intensity and stage-dependent pattern of immunoexpression of inhibin alpha, SGP-1, and AR were virtually absent at 25 days but were present by 35 days. Germ cell volume per Sertoli cell was reduced in GnRHa- and DES-treated rats compared with controls at 18 and 25 days but was significantly greater (p < 0. 001) in DES- than in GnRHa-treated rats at 35 days. The proportion of apoptotic to viable germ cells was increased (p < 0.01) in GnRHa- and DES-treated rats compared with controls at 18 and 25 days; but at 35 days, values in GnRHa-treated rats had declined to control values whereas those for DES-treated rats remained 10-fold elevated (p < 0.001). In adulthood, testis weight and daily sperm production were reduced by 43% and 44%, respectively, in GnRHa-treated rats, but spermatogenesis was grossly normal. Comparable changes were observed in approximately 25% of DES-treated rats, but the majority exhibited > 60% reduction in testis weight with many Sertoli cell-only tubules and very low daily sperm production. Taken together, these data are interpreted as providing evidence for direct modulation of Sertoli cell (maturational) development by DES.

Aging↗
PubMed1998

Complications in 100 living-liver donors.

OBJECTIVE: A review of 100 living-liver donors was performed to evaluate the perisurgical complications of the procedure and thus to help quantify the risks to the donor. SUMMARY BACKGROUND DATA: Despite the advantages of living-donor liver transplantation (LDLT), the procedure has received criticism for the risk it imposes on healthy persons. A paucity of data exists regarding the complications and relative safety of the procedure. METHODS: One hundred LDLTs performed between November 1989 and November 1996 were reviewed. Donor data were obtained by chart review, anesthesia records, and the computerized hospital data base. Patient variables were compared by Fisher's exact test and the Student's t test. RESULTS: There were 57 women and 43 men with a median age of 29. Donors were divided into two groups: group A (first 50 donors), and group B (last 50 donors). There were 91 left lateral segments and 9 left lobes. There were no deaths. Fourteen major complications occurred in 13 patients; 9 occurred in group A and 5 in group B. Biliary complications consisted of five bile duct injuries (group A = 4, group B = 1) and two cut edge bile leaks. Complications were more common in left lobe resections (55%) than in left lateral segment grafts (10%). Minor complications occurred in 20% of patients. A significant reduction in overall complications (major and minor) was observed between the groups (group A, n = 24 [45%] vs. group B, n = 10 [20%]). In addition, surgical time and hospital stay were both significantly reduced. CONCLUSIONS: Although the procedure is safe, many LDLT donors have a perisurgical complication. Surgical experience and technical modifications have resulted in a significant reduction in these complications, however. To minimize the risks for these healthy donors, LDLT should be performed at institutions with extensive experience.

Adult↗
PubMed1998

Effects of ovariectomy and hindlimb unloading on skeletal muscle.

Female rats (7-8 mo old, n = 40) were randomly placed into the intact control (Int) and ovariectomized control (Ovx) groups. Two weeks after ovariectomy, animals were further divided into intact 2-wk hindlimb unloaded (Int-HU) and ovariectomized hindlimb unloaded (Ovx-HU). We hypothesized that there would be greater hindlimb unloading-related atrophy in Ovx than in Int rats. In situ contractile tests were performed on soleus (Sol), plantaris (Plan), peroneus longus (Per), and extensor digitorum longus (EDL) muscles. Body weight and Sol mass were approximately 22% larger in Ovx than in Int group and approximately 18% smaller in both HU groups than in Int rats (Ovx x HU interaction, P < 0.05), and there was a similar trend in Plan muscle (P < 0.07). There were main effects (P < 0.05) for both ovariectomy (growth) and hindlimb unloading (atrophy) on gastrocnemius mass. Mass of the Per and EDL muscles was unaffected by either ovariectomy or hindlimb unloading. Time to peak twitch tension for EDL and one-half relaxation times for Sol, Plan, Per, and EDL muscles were faster (P < 0.05) in Ovx than in Int animals. The results suggest that 1) ovariectomy led to similar increases of approximately 20% in body weight and plantar flexor mass; 2) hindlimb unloading may have prevented ovariectomy-related muscle growth; 3) greater atrophy may have occurred in Sol and Plan of Ovx animals compared with controls; and 4) removal of ovarian hormonal influence decreased skeletal muscle contraction times.

Animals↗
PubMed1998

Immunoexpression of aquaporin-1 in the efferent ducts of the rat and marmoset monkey during development, its modulation by estrogens, and its possible role in fluid resorption.

Recent data suggest that estrogens play a role in regulating fluid resorption from the efferent ducts, though the biochemical mechanisms involved are unknown. The present study has used immunocytochemistry to localize a water channel protein, Aquaporin-1 (AQP-1), to the efferent ducts of male rats and marmoset monkeys from perinatal life through to adulthood and has then investigated its potential hormonal regulation in neonatal/peripubertal life, via administration of a GnRH antagonist (GnRHa) or diethylstilbestrol (DES) to rats. AQP-1 was immunoexpressed intensely in the apical brush border of the epithelium lining the efferent ducts at all ages studied, from late fetal life through puberty to adulthood. In the marmoset, but not the rat, AQP-1 was also expressed in the epithelium of the rete testis. Once the cell types within the efferent duct epithelium had differentiated, it was clear that only nonciliated cells of the rat localized AQP-1. When gonadotropin secretion was suppressed in rats by neonatal administration of GnRHa, immunoexpression of AQP-1 at age 18 and 25 days was virtually unchanged in intensity, though the efferent ducts were reduced in size. In contrast, when DES was administered neonatally to rats (up to day 12), immunoexpression of AQP-1 was reduced at day 10, virtually abolished at day 18, reduced markedly at day 25 and to a small extent at day 35; these findings were confirmed by Western blot analysis at day 18. The DES-induced decrease in immunoexpression of AQP-1 was accompanied by pronounced distension of the efferent ducts and rete, consistent with reduced fluid resorption. The epithelial cells of the efferent ducts in DES-treated rats were cuboidal rather than columnar in shape as in controls and were reduced significantly in height compared with controls at all ages through to adulthood. These findings suggest that estrogens may play a role in regulating fluid resorption from the efferent ducts during fetal/neonatal development and/or a role in the gross and functional development of the efferent ducts and rete testis. The present data also suggest that AQP-1 is one of the elements involved in the regulation of fluid resorption in the efferent ducts. The importance of fluid flow in fetal/neonatal development of the excurrent duct system of the male is also suggested by these observations.

Absorption↗
PubMed1998

Expression of oestrogen receptor beta (ER beta) occurs in multiple cell types, including some germ cells, in the rat testis.

The identification of a second oestrogen receptor (beta) has prompted a re-evaluation of the potential sites of action of oestrogens. The aim of the present study was to characterize immunoexpression of ER beta expression in the testis to complement earlier data which had demonstrated that expression of ER alpha is confined to testicular interstitial Leydig cells. In all testes studied, including those from both fetal (day 20.5 p.c.) and adult rats, ER beta was found to be expressed in multiple cell types. Sertoli cell nuclei were immunopositive at all ages. In adult testes expression in Sertoli cells was not stage dependent and was unaffected by ablation of Leydig cells. In fetal testes ER beta was also expressed in peritubular cells, fetal Leydig cells and gonocytes. In the pubertal and adult testis ER beta was detected in the nuclei of spermatogonia and most pachytene spermatocytes. Weak immunopositive staining was present in the cytoplasm of spermatocytes undergoing the second meiotic division. In conclusion the widespread expression of ER beta in the testis is consistent with a role for oestrogens in modulating spermatogenesis, and hence fertility, in the male.

Animals↗
PubMed1997

Fetal and perinatal influence of xenoestrogens on testis gene expression.

The incidence of reproductive abnormalities in the male has been reported to have increased during the past 50 years. It has been suggested that these changes may be attributable to the presence of chemicals with oestrogenic activity in our environment. The aim of the experiments described in this chapter was to investigate the effects of acute exposure to high levels of xenoestrogens either indirectly during fetal life, or directly during neonatal life, on gene expression in the testis and pituitary. Fetal treatment involved administration of diethylstilbestrol (DES), 4-octylphenol (OP) or vehicle (oil, control) to pregnant rats on days 11.5 and 15.5 post coitum; fetuses were recovered on day 17.5. There was no difference between fetuses from control and treated mothers in either the overall histology of the testes or numbers of Leydig cells as determined by immunohistochemistry with an antibody directed against 3 beta-HSD. However there was a consistent and striking reduction in the amount of P450 17-a hydroxylase C17, 20 lyase (P450c17) and steroidogenic factor 1 (SF-1) detected by immunocytochemistry in testes from treatment groups given the higher doses of OP and DES. Oestrogen receptors (ER alpha) were present in the fetal leydig cells of all animals. Neonatal treatment involved direct injection of oil (control), DES, OP or Bisphenol A (Bis A) on days 2, 4, 6, 8, 10 and 12; pituitaries and testes were recovered on day 18. Testis weights and seminiferous tubule diameters were significantly reduced in animals treated with DES. In these same animals immunocytochemical localisation revealed that the amounts of FSH beta subunit and inhibin alpha subunit were reduced in their pituitaries and testes respectively. OP did not appear to have an acute, measurable effect on testis gene expression but a reduction in testis weight was noted in adult animals given the same treatment regime. The effects observed are consistent with negative feedback by oestrogens on pituitary production of FSH resulting in retarded maturation of seminiferous tubules and reduced Sertoli cell numbers. These studies have demonstrated that administration of high levels of oestrogens can affect gene expression in the testis early in life. However, the relevance of these findings to observations in man await a) a greater understanding of the physiological role(s) of oestrogens in normal males, b) an evaluation of the sources, routes of exposure, concentrations in vivo and bioavailability of xenoestrogens.

Animals↗
PubMed1997

Regional differences in interstitial glycerol concentration in subcutaneous adipose tissue of women.

The aims of this study were to 1) compare two methods of determining interstitial glycerol concentration in subcutaneous adipose tissue (AT) and 2) determine whether there are regional differences in interstitial glycerol concentration in subcutaneous AT of nonobese, premenopausal women. Microdialysis probes were inserted under local anesthesia into the abdominal (2 probes) and femoral (1 probe) subcutaneous AT in each subject (n = 5) and perfused with a Ringer solution containing 2.5 mM glucose and glycerol in concentrations ranging from 0 to 900 microM. Microdialysis probe relative recoveries and interstitial glycerol concentrations were determined by the no-net-flux method (NNF) and the internal reference method (IR) with the use of [13C]glycerol. Microdialysis probe relative recoveries were 57.4 +/- 3.6% by NNF and 61.2 +/- 10.1% by IR in femoral AT [P = not significant (NS)] and were 55.2 +/- 6.0% by NNF and 66.6 +/- 4.2% by IR in abdominal AT (P = NS). The calculated interstitial glycerol concentrations determined by NNF and IR were 236.4 +/- 42.7 and 241.1 +/- 39.6 microM (P = NS) in femoral AT and 151.4 +/- 29.7 and 129.4 +/- 18.7 microM in abdominal AT (NNF vs. IR, P = NS; femoral vs. abdominal, P < 0.05). It can be concluded that the interstitial glycerol concentration in the femoral AT of nonobese, premenopausal females is approximately 240 microM and is higher than in abdominal AT (140 microM). Furthermore, the use of a stable isotope of glycerol as an internal reference is suitable for determining interstitial glycerol concentrations in subcutaneous adipose tissue in humans at rest.

Abdomen↗
PubMed1997

Role of nitric oxide in skeletal muscle blood flow at rest and during dynamic exercise in humans.

The role of nitric oxide at rest and in the active hyperemic response within skeletal muscle was investigated in eight physically active men. Three microdialysis probes were inserted into the vastus lateralis of the quadriceps femoris muscle group in each subject. Microdialysis probes were perfused with a Ringer solution containing 5.0 mM ethanol, 2.5 mM glucose, and either 10 mg/ml of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) monoacetate salt, 30 mg/ml of the nitric oxide precursor L-arginine, or no additional substance (control probe). Subjects performed one-legged cycling exercise at work rates ranging from 25 to 100 W. Dialysate and perfusate ethanol concentrations were presented as the ratio of [ethanol]dialysate to [ethanol]perfusate (ethanol outflow-to-inflow ratio), an indicator that is inversely related to blood flow. The ethanol outflow-to-inflow ratios at rest were 0.614 +/- 0.032, 0.523 +/- 0.023, and 0.578 +/- 0.039 in the L-NMMA, L-arginine, and control probes, respectively. Calculated resting blood flows were therefore 8.7 +/- 4.1, 20.5 +/- 4.6, and 14.0 +/- 4.7 ml.min-1.100 g-1 around the L-NMMA, L-arginine, and control probes, respectively. The ethanol outflow-to-inflow ratios were significantly higher at all exercise intensities in the L-NMMA probe than in the control and L-arginine probes, resulting in calculated blood flows of 195 +/- 55, 407 +/- 47, and 352 +/- 60 ml.min-1.100 g-1 at 25 W and 268 +/- 65, 602 +/- 129, and 519 +/- 113 ml.min-1.100 g-1 at 100 W around the L-NMMA, L-arginine, and control probes, respectively. Skeletal muscle blood flow was therefore reduced both at rest and during continuous, dynamic exercise by the action of L-NMMA, whereas blood flow was increased only at rest by L-arginine.

Adult↗
PubMed1997

Muscle glycogen accumulation after endurance exercise in trained and untrained individuals.

Muscle glycogen accumulation was determined in six trained cyclists (Trn) and six untrained subjects (UT) at 6 and either 48 or 72 h after 2 h of cycling exercise at approximately 75% peak O2 uptake (VO2 peak), which terminated with five 1-min sprints. Subjects ate 10 g carbohydrate . kg-1 . day-1 for 48-72 h postexercise. Muscle glycogen accumulation averaged 71 +/- 9 (SE) mmol/kg (Trn) and 31 +/- 9 mmol/kg (UT) during the first 6 h postexercise (P < 0.01) and 79 +/- 22 mmol/kg (Trn) and 60 +/- 9 mmol/kg (UT) between 6 and 48 or 72 h postexercise (not significant). Muscle glycogen concentration was 164 +/- 21 mmol/kg (Trn) and 99 +/- 16 mmol/kg (UT) 48-72 h postexercise (P < 0.05). Muscle GLUT-4 content immediately postexercise was threefold higher in Trn than in UT (P < 0.05) and correlated with glycogen accumulation rates (r = 0.66, P < 0.05). Glycogen synthase in the active I form was 2.5 +/- 0.5, 3.3 +/- 0.5, and 1.0 +/- 0.3 micromol . g-1 . min-1 in Trn at 0, 6, and 48 or 72 h postexercise, respectively; corresponding values were 1.2 +/- 0.3, 2.7 +/- 0.5, and 1.6 +/- 0.3 micromol . g-1 . min-1 in UT (P < 0.05 at 0 h). Plasma insulin and plasma C-peptide area under the curve were lower in Trn than in UT over the first 6 h postexercise (P < 0.05). Plasma creatine kinase concentrations were 125 +/- 25 IU/l (Trn) and 91 +/- 9 IU/l (UT) preexercise and 112 +/- 14 IU/l (Trn) and 144 +/- 22 IU/l (UT; P < 0.05 vs. preexercise) at 48-72 h postexercise (normal: 30-200 IU/l). We conclude that endurance exercise training results in an increased ability to accumulate muscle glycogen after exercise.

Adult↗
PubMed1997

Immunolocalisation of oestrogen receptor-alpha within the testis and excurrent ducts of the rat and marmoset monkey from perinatal life to adulthood.

The sites of action and the physiological role of oestrogens in the male reproductive tract are poorly understood. We have undertaken a systematic study of the immunoexpression of oestrogen receptor-alpha (ER alpha) in the male rat from late fetal life through to adulthood and compared the findings with results obtained in the marmoset monkey (Callithrix jacchus) from neonatal to adult life. The testes, rete testis, efferent ducts and epididymis were examined from normal male rats (aged 4, 8, 10, 15, 20, 25, 38, 48 and 90 days) and from male rat fetuses on days 17.5 and 18.5 of gestation; comparable tissues were examined from neonatal, infantile, peripubertal and adult marmosets aged 8, 18-24, 54-62 and 92-112 weeks respectively. Immunolocalisation of ER alpha used antigen retrieval and a monoclonal antibody directed to the N-terminus, which had proved superior to six other antisera tested. ER alpha was immunoexpressed in interstitial cells, including the fetal/ neonatal generation of Leydig cells, in both the rat and marmoset. In the rat, the adult generation of Leydig cells were also immunopositive for ER alpha whereas the comparable cells in the marmoset were only weakly immunopositive. ER alpha was not expressed in Sertoli cells, peritubular myoid cells, blood vessels or germ cells at any time in either species. In late fetal life in the rat, ER alpha was immunoexpressed in cells surrounding the mesonephric tubules, whereas postnatally it was expressed in the epithelium of the rete testis and efferent ducts at all ages from 4 to 90 days; this immunoexpression was most pronounced in the efferent ducts. In the marmoset, the efferent ducts, but not the rete testis, also showed intense immunoexpression of ER alpha. Apart from sporadic immunostaining for ER alpha in the epididymal duct of the rat in the neonatal period, the caput, corpus and cauda epididymis were negative for immunoexpression of ER alpha at all ages in both species. These findings suggest that the main actions of oestrogens in the male reproductive tract, mediated by ER alpha, are related to the development and function of the efferent ducts and the Leydig cells. In consideration of data from this and previous studies of oestrogen binding, we predict possible sites of expression of other oestrogen receptors (e.g. ER beta) in Sertoli cells and the epididymis. Interactive effects, related to the relative levels of androgens and oestrogens, could be physiologically important in the excurrent ducts of the adult testis.

Age Factors↗
PubMed1996

A locus on the X chromosome is linked to body length in mice.

Linkage between body length (anus to nose (AN) length) and three markers on the mouse X Chromosome was found in an interspecific backcross ((C57BL/6J x Mus spretus) F 1x C57BL/6J), designated BSB. A cross of 409 mice were scored for 148 genetic markers distributed on all chromosomes except the Y Chromosome. Statistical analysis revealed highly significant linkage (LOD score 5.5) between body length and a locus in the middle portion of the X Chromosome, the nearest markers being the microsatellite marker DXMit73 and a farnesyl pyrophosphate locus (Fpsl9) 3.1 cM proximal to DXMit73. The locus explains 10% of the variance in AN length and affects both males and females to about the same extent.

Animals↗
PubMed1995

Gestational and lactational exposure of rats to xenoestrogens results in reduced testicular size and sperm production.

This study assessed whether exposure of male rats to two estrogenic, environmental chemicals, 4-octylphenol (OP) and butyl benzyl phthalate (BBP) during gestation or during the first 21 days of postnatal life, affected testicular size or spermatogenesis in adulthood (90-95 days of age). Chemicals were administered via the drinking water or concentrations of 10-1000 micrograms/l (OP) or 1000 micrograms/l (BBP), diethylstilbestrol (DES; 100 micrograms/l) and an octylphenol polyethoxylate (OPP; 1000 micrograms/l), which is a weak estrogen or nonestrogenic in vitro, were administered as presumptive positive and negative controls, respectively. Controls received the vehicle (ethanol) in tap water. In study 1, rats were treated from days 1-22 after births in studies 2 and 3, the mothers were treated for approximately 8-9 weeks, spanning a 2-week period before mating throughout gestation and 22 days after giving birth. With the exception of DES, treatment generally had no major adverse effect or body weight: in most instances, treated animals were heavier than controls at day 22 and at days 90-95. Exposure to OP, OPP, or BBP at a concentration of 1000 micrograms/1 resulted in a small (5-13%) but significant (p < 0.01 or p < 0.0001) reduction in mean testicular size in studies 2 and 3, an effect that was still evident when testicular weight was expressed relative to body, weight or kidney weight. The effect of OPP is attributed to its metabolism in vivo to OP. DES exposure caused similar reductions in testicular size but also caused reductions in body weight, kidney weight, and litter size. Ventral prostate weight was reduced significantly in DES-treated rats and to minor extent in OP-treated rats. Comparable but more minor effects of treatment with DES or OP on testicular size were observed in study 1. None of the treatments had any adverse effect on testicular morphology or on the cross-sectional area of the lumen or seminiferous epithelium at stages VII-VIII of the spermatogenic cycle, but DES, OP, and BBP caused reductions of 10-21% (p < 0.05 to p < 0.001) in daily sperm production. Humans are exposed to phthalates, such as BBP, and to alkylphenol polyethoxylates, such as OP, but to what extent is unknown. More detailed studies are warranted to assess the possible risk to the development of the human testis from exposure to these and other environmental estrogens.

Animals↗