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Chronic administration of neuropeptide Y into the lateral ventricle inhibits both the pituitary-testicular axis and growth hormone and insulin-like growth factor I secretion in intact adult male rats.

Neuropeptide Y (NPY) is known to be involved in the central regulation of appetite, sexual behavior, and reproductive function. Whereas central administration of NPY strongly stimulates feeding in satiated animals, diet restriction or other unfavorable metabolic situations, such as diabetes, produce enhanced NPY gene expression and NPY release in the hypothalamus. Numerous studies have indicated that acute central administration of NPY results in various actions on LH secretion in the rat, either stimulatory or inhibitory. We recently demonstrated that chronic infusion of NPY into the lateral ventricle of adult intact female rats profoundly inhibited both the gonadotropic and somatotropic axes, with disruption of estrous cyclicity. Furthermore, we showed that central chronic infusion of NPY delayed sexual maturation in female rats. To analyze the effects of the same type of chronic NPY treatment on the pituitary-testicular axis, 45-day-old Sprague-Dawley male rats were implanted with stainless steel cannulas in the right lateral ventricle. Ten days later, Alzet osmotic minipumps were filled with different NPY solutions, adjusted to deliver 6, 18, or 36 micrograms/day, connected to the intracerebroventricular (icv) cannula, and sc implanted dorsally. The effects of these treatments were evaluated over 7 days. In one case, rats were castrated 5 days after initiation of NPY treatment, and the effect of castration was evaluated 2 days later. Chronic icv infusion of NPY produced the expected dose-related increases in food intake from 33.0 +/- 0.9 (basal) to 53.4 +/- 3.3 g/day (18 micrograms NPY/day) and body weight gain (5.7 +/- 0.7 to 10.5 +/- 1.2 d/day). As in female rats, this orexigenic action of NPY resulted in a significant dose-related decrease in pituitary weight, from 12.4 +/- 0.7 to 9.9 +/- 0.4 mg. The 7-day NPY infusion produced highly significant decreases in seminal vesicle weight (853 +/- 77 to 230 +/- 31 mg) and testis weight (3.82 +/- 0.09 to 3.18 +/- 0.15 g; P = 0.003). Plasma levels of testosterone (231 +/- 71 to 48 +/- 13 ng/dl), LH (20.7 +/- 3.7 to 9.1 +/- 1.2 ng/ml), and FSH (282 +/- 17 to 190 +/- 18 ng/ml) were markedly decreased at the 18 micrograms/day dosage, as also demonstrated for the 36 micrograms/day dosage. None of these effects was observed if vehicle was infused into the lateral ventricle instead of the NPY solution. When bilateral orchidectomy was performed 5 days after initiation of the NPY infusion (18 micrograms/day), the immediate LH and FSH rises usually seen after castration were seriously blunted.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Nitrofurazone: reproductive assessment by continuous breeding in Swiss mice.

Nitrofurazone (NTFZ), a nitrofuran antibiotic, was evaluated for reproductive toxicity in Swiss CD-1 mice using the Reproductive Assessment by Continuous Breeding protocol. Male and female mice were cohabited for 15 weeks and exposed to NTFZ in feed at concentrations of 0, 100, 375, and 750 ppm (14-102 mg/kg/day). Fzero 750-ppm breeding pairs had significantly reduced fertility after 7 days of exposure to NTFZ (17% fertile compared to 98% for control pairs) and were infertile after the second litter. Fzero mid-dose pairs had progressively decreasing fertility (47% by the fifth litter), reduced litter size, and reduced proportion of pups born alive. Crossover breeding of control and high-dose Fzero animals confirmed infertility in high-dose males and reduced litter size and pup weight in high-dose females when compared to the control x control group. At necropsy, there were no effects on body weight, but Fzero males had reduced testis weight at the high dose and reduced epididymal sperm concentration and abnormal sperm morphology at all doses of NTFZ. Increased liver as well as kidney and adrenal weights (combined) were observed at 375 and 750 ppm; hepatic hypertrophy was noted microscopically at 750 ppm. Fzero females had reduced body weight, hepatic hypertrophy, and altered estrous cycles at 750 ppm and reduced ovarian weight at all doses. In the second generation, F1 mice at 375 ppm had reduced postnatal survival and body weight and produced smaller F2 litters compared to control mice. At necropsy, F1 males had reduced testes weight and epididymal sperm concentration, abnormal sperm morphology, hepatic hypertrophy at 375 ppm, and borderline nephropathy at 100 and 375 ppm. F1 females had decreased body, liver, and ovarian weight at 375 ppm and altered estrous cycles at 100 and 375 ppm. Thus, NTFZ at > or = 100 ppm (> or = 14 mg/kg/day) caused adverse reproductive effects in Fzero male and female and F1 female mice in the presence of relatively mild systemic toxicity.

Animals↗

Lithium and the neonate: developmental and metabolic aspects.

The interrelationship between lithium salts, which has been used in clinical trials of alcoholism, and ethanol, which evoke fetal alcohol syndrome by chronic use, was studied. This was made by evaluating the effect of prenatal and postnatal exposure to LiCl on ethanol and acetaldehyde metabolizing enzymes in the newborn mouse. The three Li-treatment regimens made consisted of acute and short-term prenatal exposure to LiCl in addition to postnatal exposure until weaning of the neonates. The weaned mice were then kept on water for a subsequent two weeks prior to sacrifice. The effects of LiCl, given in drinking fluid, on body weight, selected organ weights, hepatic alcohol dehydrogenase, aldehyde dehydrogenase and heart lactate dehydrogenase of the offspring were determined. Prenatal and postnatal ingestion of LiCl by the nursing mother resulted in decreased brain weight of offspring from both sexes. Concomitantly, there was a reduction in female but not male kidney weight. A marked decrease in the testis weight also occurred. The Li-treatment induced both neonatal hepatic alcohol dehydrogenase and heart lactate dehydrogenase in both sexes. Conversely, an inhibition of hepatic mitochondrial aldehyde dehydrogenase, for the enzyme with the apparent high Km, was determined in the male offspring. Maternal postnatal ingestion of LiCl decreased brain and spleen weights from corresponding control of neonatal male and female, respectively. This Li-treatment also induced hepatic neonatal alcohol dehydrogenase in both sexes. The results suggest that maternal ingestion of LiCl may interfere in brain development.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Dehydrogenase↗

Permanent effects of neonatal estrogen exposure in rats on reproductive hormone levels, Sertoli cell number, and the efficiency of spermatogenesis in adulthood.

This study aimed to identify the mechanism(s) for impairment of spermatogenesis in adulthood in rats treated neonatally with estrogens. Rats were treated (days 2-12) with 10, 1, or 0.1 microg diethylstilbestrol (DES), 10 microg ethinyl estradiol (EE), 10 mg/kg of a GnRH antagonist (GnRHa), or vehicle and killed in adulthood. DES/EE caused dose-dependent reductions in testis weight, total germ cell volume per testis, and Sertoli cell volume per testis. Sertoli cell number at 18 days of age in DES-treated rats was reduced dose dependently. GnRHa treatment caused changes in these parameters similar to those in rats treated with 10 microg DES. Plasma FSH levels were elevated (P < 0.001) to similar levels in all treatment groups regardless of differences in Sertoli cell number and levels of inhibin B; the latter reflected Sertoli cell number, but levels were disproportionately reduced in animals treated with high doses of DES/EE. Neonatal estrogen treatment, but not GnRHa, caused dose-dependent reductions (40-80%) in plasma testosterone levels in adulthood, but did not alter LH levels. Preliminary evidence suggests that the decrease in testosterone levels in estrogen-treated rats is not due to reduced Leydig cell volume per testis. GnRHa-treated rats exhibited a significant increase in germ cell volume per Sertoli cell and a reduction in germ cell apoptosis, probably because of the raised FSH levels. Despite similar raised FSH levels, rats treated with DES (10 or 1 microg) or EE (10 microg) had reduced germ cell volume/Sertoli cell and increased germ cell apoptosis, especially when compared with GnRHa-treated animals. The latter changes were associated with an increase in lumen size per testis, indicative of impaired fluid resorption from the efferent ducts, resulting in fluid accumulation in the testis. Rats treated neonatally with 0.1 microg DES showed reduced germ cell apoptosis comparable to that in GnRHa-treated animals. The changes in apoptotic rate among treatment groups occurred across all stages of the spermatogenic cycle. It is concluded that 1) neonatal estrogen treatment results in dose-dependent alterations in Sertoli cell numbers, germ cell volume, efficiency of spermatogenesis, and germ cell apoptosis in adulthood; 2) the relatively poor spermatogenesis in estrogen-treated animals is most likely due to altered testis fluid dynamics and/or altered Sertoli cell function; 3) as indicated by FSH (LH) and testosterone levels, the hypothalamic-pituitary axis and Leydig cells are probably more sensitive than the Sertoli cells to reprogramming by estrogens neonatally; and 4) elevated FSH levels in adulthood may improve the efficiency of spermatogenesis.

Animals↗

Male reproductive toxicity study of nitrazepam in rats.

The main focus of this study is the optimal administration period concerning toxic effects on male fertility in rats. To assess functional and morphological changes induced in the testis by nitrazepam, male rats were administered the drug at doses of 0, 20, 40 or 80 mg/kg during pre-mating periods of 2, 4 or 9 weeks and then the 2 weeks of mating. At the end of the administration period the animals were sacrificed and sperm number, motility, abnormalities and histopathological changes in the testis were examined. Decreases in testis weight, epididymis weight, number of sperm in the testis and sperm motility were observed in the 40 and 80 mg/kg sections of the 2, 4 and 9 week pre-mating treated groups. Mating with untreated females revealed no adverse effects on copulation rate in any group; however, a remarkable decrease in pregnancy rate was noted in the 80 mg/kg section of the 2, 4 and 9 week treated groups. On histological examination, various degrees of localized necrosis in the seminiferous epithelium and Leydig cell hyperplasia were observed in the testis. No clear changes were observed in the 20 mg/kg section of the 2 week pre-mating administration group, but at the 4 week time point, necrosis of spermatogenic cells began to appear. The primary morphological event was evident in spermatocytes with necrosis of the cytoplasm observed from 4 weeks after administration of nitrazepam, although sperm motility and sperm head counts were unaffected. From these findings, examination of sperm characteristics and histopathological changes in the testis are important parameters for evaluation of drugs inducing testicular damage. We conclude that a 4 week administration period is sufficient to detect effects of nitrazepam on male fertility.

Animals↗

Performance of male pigs immunized against GnRH is related to the time of onset of biological response.

In this study, the performance of male pigs immunized against GnRH was determined in relation to the onset of their biological response to the immunization. Pigs were immunized at 9 and 17 wk of age and were housed in a pen together with both a surgically castrated and an intact boar littermate. Feed intake was restricted to 2.8 to 3.2 times maintenance requirement for energy. Animals were weighed weekly and slaughtered at 108 kg BW. Depending on the time of onset of the response after immunization in terms of biological effects, immunized pigs were retrospectively grouped into two categories. One category consisted of the immunized pigs, which had undetectable or low levels of LH and testosterone at the time of booster immunization-known as "early" responding immunocastrates (E-IM, n = 8), whereas the "late" responding immunocastrates (L-IM, n = 7) had substantial LH and testosterone levels at that time. This dichotomy of the response to immunization also was reflected in testis weight, with 17 g and 40 g for E-IM and L-IM pigs, respectively. At slaughter, testis size and weight were reduced (P < 0.001) in the immunocastrated pigs as compared to the intact boars. Androstenone concentrations in backfat of all immunocastrated pigs were undetectable. Growth performance (i.e., ADG and feed efficiency [FE, g gain/kg feed]), was better in boars and L-IM pigs than in surgical castrates and E-IM pigs (P < 0.05). Average daily gain and FE did not differ between E-IM pigs and the surgical castrates, but intact boars performed better than L-IM (P < 0.02). There were no significant differences in carcass quality (backfat thickness and meat percentage) between boars and surgical castrates at slaughter. However, for both characteristics L-IM pigs and intact boars performed better (P < 0.03) than E-IM pigs. Thus, growth performance in L-IM is better than in either E-IM or surgical castrates.

Androstenes↗

Insights into testicular damage induced by ethinylestradiol in rats.

The present study was conducted to clarify the mechanisms of testicular toxicity induced by ethinylestradiol using a rat model maintaining testicular testosterone levels. Twelve-week-old male SD rats were implanted subcutaneously with testosterone (800 mg)-filled tubes on the back 2 days before ethinylestradiol treatment, and subsequently administered orally 10 mg/kg/day ethinylestradiol for 4 consecutive weeks. At termination, measurements of hormone levels in serum and the testis, sperm head counts in the testis, weights of genital organs and histopathological examination were performed. Results show that the supply of testosterone alone induced markedly increased serum testosterone levels, slightly decreased testicular testosterone levels, and atrophic Leydig cells. Treatment of rats with ethinylestradiol alone significantly decreased testosterone levels in serum and the testis, sperm head counts, and weights in the testis, epididymis and prostate. Histological features included atrophy of Leydig cells, decreased number of elongated spermatids, degeneration of germ cells, and tubular atrophy. Co-administration of testosterone almost completely prevented the aforementioned changes brought about by ethinylestradiol, except for Leydig cell atrophy. From these results, we attribute testicular toxicity during ethinylestradiol exposure to the suppression of testicular testosterone levels.

Administration, Oral↗

Monosodium glutamate admlinistration to the newborn reduces reproductive ability in female and male mice.

Monosodium glutamate (MSG) administered during the neonatal period (days 2 to 11) resulted in a sequence of events that were manifested in adulthood. Reproductive dysfunction was seen in both female and male animals. Females treated with MSG had fewer pregnancies and smaller litters, while males treated with MSG showed reduced fertility. The MSG-treated mice showed increased body weight and decreased pituitary, thyroid, ovary, or testis weights.

Adrenal Glands↗

Biological effects of long-term caloric restriction: adaptation with simultaneous administration of caloric stress plus repeated immobilization stress in rats.

In the present study, we have established the biological effects during 8 weeks of (i) caloric restriction (Cal) and (ii) simultaneous administration of Cal plus 2 hr daily immobilization stress using male Sprague-Dawley rats. Animals were divided into three equal groups: (i) ad libitum fed, (ii) 30% restriction of food intake of the ad libitum diet, and (iii) 30% restriction of food intake plus 2 hr daily immobilization stress. Caloric-restricted animals gained only 30% of the total body weight of the unrestricted animals but received 70% of the food of those rats. Cal animals showed a significant loss in their relative liver and-thymus weight and a significant gain in their relative adrenal and testis weight as compared to the control animals. Cal animals had almost 2-fold higher levels of plasma corticosterone levels with a dramatic decrease in the total glucocorticoid receptor (GR) levels in the liver, thymus, heart, and testis as compared to ad libitum fed control animals. Interestingly, Cal animals showed higher levels of lipid peroxidation in both the liver and heart, indicating increased oxidative activities in these tissues when compared with the control animals. In addition, Cal animals had increased heat shock protein 70 (HSP 70) content in the testis. Surprisingly, hardly any significant differences were observed in either total body weight gain, organ weights, plasma corticosterone levels, or lipid peroxidation between Cal animals and Cal plus immobilization-stressed animals. The results obtained suggest that (i) several stress-related responses such as inhibition of total body weight gain, increased adrenal weight, decreased thymus weight, increased plasma corticosterone, and lipid peroxidation levels in the liver and heart are associated with Cal, but (ii) no additional effects were observed on the parameters that were measured when two stress regimens were given simultaneously, suggesting that animals subjected to two stress regimens can protect themselves by controlling their stress-related thresholds of response through adaptation.

Adaptation, Biological↗

Effects of a new platinum complex on male fertility in rats--collaborative work to determine the optimal period and optimal parameters to detect effects on male fertility in rats.

To assess the testicular toxicity induced by compound C, a new platinum complex being developed as an anti-cancer drug, the substance was intravenously administered to male rats at doses of 1, 3 and 10 mg/kg/day for 4 weeks and at doses of 0.3, 1 and 3 mg/kg/day for 9 weeks. Males were cohabited with non-treated females after these treatment periods and at sacrifice the genital organ weights and number of sperm in the testis were recorded and a histopathological examination performed. The females were sacrificed on day 13 of gestation and the numbers of corpora lutea, implantations and resorptions were counted. In the 4 weeks treatment 10 mg/kg/day group, the testis weight increased while the weights of the epididymides, seminal vesicles and prostate decreased significantly, and the number of sperm was significantly decreased. Extension of seminiferous tubules, vacuolization of spermatocytes, spermatids and Sertoli cells, and degeneration of spermatocytes and spermatids were observed by histopathological examination. Copulation and impregnation were not affected by treatment but the implantation rate was significantly decreased in the 10 mg/kg/day group. These results show that compound C has testicular toxicity like other platinum complexes and that organ weight, number of sperm, number of implantation and histopathological examination are useful for detection purposes. Treatment with compound C for 9 weeks did not affect male reproductive function in spite of severe general toxicity. This suggests that testicular toxicity should be detected after 4 weeks rather than 9 weeks treatment.

Animals↗

Dissociating antifertility effects of GnRH-antagonist from its adverse effects on mating behavior in male rats.

Antagonist analogues of gonadotropin-releasing hormone (GnRH-A) alone inhibit spermatogenesis in experimental animals, but concomitant decline in serum testosterone leads to abolition of mating behavior. We assessed if the antifertility effects of GnRH-A could be dissociated from its effects on mating behavior by combining it with a small dose of androgen. Seven groups of six adult male Wistar rats were treated for 70 days as follows: I) controls, II) GnRH-A alone (250 micrograms/day), III) GnRH-A + 0.05 mg testosterone enanthate (TE), IV) GnRH-A + 0.15 mg TE, V) GnRH-A + 0.50 mg TE, VI) GnRH-A + 1.50 mg TE, and VII) GnRH-A alone (recovery group). Testes, prostate, and seminal vesicle weights were markedly reduced by GnRH-A treatment alone. Doses of TE required to maintain prostate and seminal vesicle weights were between 0.15 and 0.50 mg. Testis weights were not restored to normal even by the highest dose of TE. Intratesticular sperm counts were markedly decreased by GnRH-A treatment and restored only at the highest dose of TE (1.50 mg). Five out of six animals in group II, six out of six animals in group III, and one out of six in group IV were azoospermic. When mated with normal females, all animals in groups I and VI were fertile, all animals in groups II, III, and IV were infertile, whereas only four out of six animals in group V were fertile. All measures of mating behavior were impaired by GnRH-A treatment and restored by the smallest dose of TE (0.05 mg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of the gonadotropin-releasing hormone agonist [D-leu6, desgly-NH2(10), proethylamide9]-GnRH (leuprolide) on R3327-G rat prostatic tumor growth.

The synthetic gonadotropin releasing hormone agonist [D-leu6, desgly-NH2(10), proethylamide9]-GnRH (leuprolide) was tested for its ability to inhibit androgen-sensitive R3327-G rat prostatic tumor growth in Copenhagen X Fischer F1 male rats. The chronic administration of leuprolide at 50 micrograms per kg. body weight or 1000 micrograms per kg. body weight significantly reduced serum testosterone levels and testis weights. Only chronic leuprolide administration at high concentration (1000 micrograms per kg.) compared with orchiectomy in reducing the rate of tumor growth, prolonging survival, and affecting changes in DNA content per cell as quantitated by flow cytometry. The DNA content changes and cell kinetic responses of R3327-G tumors to these treatments were related to the extent to which serum testosterone levels were reduced. The data suggest that for some prostatic cancers gonadotropin releasing hormone agonist administration must reduce serum testosterone levels to those achieved by orchiectomy for maximal growth rate inhibition.

Animals↗

Effect of heat stress on the fertility of male mice in vivo and in vitro.

A study was conducted to determine whether following exposure of male mice to high temperatures, the ability of their spermatozoa to fertilise ova was reduced, especially during the period before the males became completely infertile. Male mice placed in a microclimate chamber at 36 degrees C for two periods, each of 12 h on successive days, were less able to fertilise control females in vivo when mated and, even in those females that became pregnant, litter size was reduced. However, these effects were associated with falls in testis weight and numbers of spermatozoa in the testis and epididymis. To determine whether the effect on fertility was a result of the decreased spermatozoa numbers, spermatozoa were collected from the epididymides of heated and control males. Equal numbers of motile spermatozoa from an unselected sample or those subjected to a swim-up procedure to separate those that were motile from the immotile ones in the sample were then mixed in vitro with oocytes from superovulated normal females. Similar numbers of spermatozoa from both control and heated males bound to the zona pellucida but smaller percentages of the oocytes were fertilised by spermatozoa from the heated males and fewer of these spermatozoa penetrated the ova. The effects were first seen 7 days after the heat exposure and became more obvious after 10 or 14 days.

Animals↗

Sensitivity of testicular germ cells to toxicant-induced apoptosis in gld mice that express a nonfunctional form of Fas ligand.

Germ cell apoptosis in testis is essential for functional spermatogenesis. Recent evidence suggests that the Fas signaling system is critical for the regulation of testicular germ cell apoptosis. To further evaluate the Fas signaling system in testis, we examined the incidence of germ cell apoptosis in gld mice that lack a functional Fas-signaling pathway. gld mice have a small, but significant, increase in testis weight and numbers of spermatid heads per testis compared with wild-type mice. In addition, gld mice have a small increase in the spontaneous incidence of germ cell apoptosis, as indicated by characteristic DNA fragmentation via the terminal deoxynucleotidyl-transferase-mediated deoxy-UTP nick end labeling assay. To test the role of the Fas system in toxicant-induced germ cell apoptosis, mice were exposed to either a Sertoli cell- or germ cell-specific toxicant [mono-(2-ethylhexyl)phthalate (MEHP; 1 g/kg) or 5 Gy radiation, respectively]. These two exposure paradigms induced extensive increases in germ cell apoptosis in wild-type mice. However, exposure of gld mice to MEHP caused only a minimal increase in germ cell apoptosis, whereas they were as sensitive as wild-type mice to radiation exposure. These data indicate that the Fas signaling pathway is 1) involved in regulating the numbers of germ cells in the testis, 2) crucial for the initiation of germ cell apoptosis after MEHP-induced Sertoli cell injury, and 3) differentially active in the cell-specific regulation of germ cell apoptosis that occurs as a consequence of Sertoli cell vs. germ cell injury.

Animals↗

Effects of photoperiod and food availability on growth, leptin, sexual maturation and maintenance in the Mongolian gerbils (Meriones unguiculatus).

Reproductive activity of Mongolian gerbils is regulated by photoperiod nevertheless body weight regulation is controlled without ambient photoperiod. Food intake is a major factor affecting rodent reproductive efficiency. Leptin is a hormone secreted by adipose tissue and modulates food intake, energy expenditure and body fat stores. In this study we studied the interaction of photoperiod and food availability on growth, sexual maturation and leptin concentration in the male and female gerbils. Gerbils were gestated and reared in either 14L:10D or 2L:22D. At weaning, gerbils were housed individually and divided into three groups: fed ad libitum, fed 80% of ad libitum or fed 60% of ad libitum. Body weights were recorded at weaning and every week thereafter. After twelve weeks of treatment, animals were sacrificed and testes and uterine weights were determined and blood was collected for leptin measurement. Food restriction reduced body weight and inhibited reproductive development. Absolute paired testis weights were similar in ad lib and 80% of ad lib groups but significantly different compared with the 60% of ad lib group in both photoperiods. Body weights were also directly dependent upon the level of food restriction. Uterine mass was only affected in the 60% of ad lib group in 14L but both food restriction levels significantly affected the uterine weights in 2L. Significant variations were found in leptin profiles. Leptin concentration was highest in ad lib and 80% of ad lib groups and lowest in 60% of ad lib groups. These results suggest that the reproductive activity of Mongolian gerbils is sensitive to food intake and multiple potential environmental cues (e.g., food availability, temperature) can be utilized.

Animals↗

Testicular sperm reserves in cockerels bearing Z-autosome translocations.

A technique of testicular homogenization and hemocytometric enumeration of elongated spermatids was applied to cockerels bearing Z-autosome translocations to estimate the effects of the translocations on sperm production. Testis weights, numbers of spermatids per gram of testis, and total number of spermatids were not significantly different between translocation-bearing cockerels and those of normal karyotype. In contrast to the adverse effects of X-autosome translocations on mammalian spermatogenesis, these data indicate that Z-autosome translocations do not quantitatively affect sperm production in cockerels.

Animals↗

Genetic parameters for testes traits in swine.

Data were collected from 1,245 Duroc boars and 527 Yorkshire boars. This represents 128 Duroc and 57 Yorkshire sires. Body weights, testis length and combined testes width at 140 and 168 d were obtained. Of these boars, 432 were castrated at a later age to evaluate relationships between in situ measures and excised testis traits. Heritabilities for testis length, width and volume at 140 d ranged from .16 to .25 in both Duroc and Yorkshire data. Heritabilities for testis measurements at 168 d ranged from .16 to .36 in both data sets. Favorable negative genetic relationships were found between in situ testis measures and age to 104 kg and backfat adjusted to 104 kg. Correlations among in situ measurements were high and positive. All excised testicular traits were highly heritable except for right epididymis weight and excised testis width. Correlation estimates among excised testis traits were generally positive. Phenotypic and genetic correlation estimates between live (in situ testis and growth performance traits) measurements and excised testis traits were generally favorable. This study suggests that in situ testis measurements should be good predictors of sperm production. It also suggests that selection for testis size should not be antagonistic to selection for growth performance traits.

Animals↗

The effects of chronic administration of pyrimethamine on spermatogenesis and fertility in male rats.

The present study examines whether the antifertility effects of pyrimethamine (PYR), an inhibitor of dihydrofolate reductase, are mediated by a reduction in intratesticular testosterone (T) concentrations or whether PYR exerts its effect by a cytotoxic insult to spermatogenic cells that is independent of intratesticular testosterone. Adult male rats were treated daily with 100 mg/kg (n = 16) or 400 mg/kg (n = 16) of PYR in honey for 8 weeks. Control rats (n = 16) received honey without PYR. Eight weeks after treatment, five rats from each PYR-treated group and five control rats were mated with normal cycling female rats, and fertility was assessed. These rats were euthanized after the fertility trial; testis weight, testicular sperm, and epididymal sperm counts were determined, and serum levels of T, LH, FSH, and seminiferous tubule fluid T (STF-T) concentrations were measured by RIA. Testes from three rats per group were perfusion-fixed for histological evaluation. PYR was discontinued in the remaining rats for 8 weeks and similar parameters were evaluated after 8 weeks of recovery. PYR (100 mg/kg/day) treatment for 8 weeks did not have any effects on organ weights, testicular and epididymal sperm counts, and hormone levels when compared to controls. In contrast, PYR (400 mg/kg/day) treatment significantly reduced testis and epididymis weights, testicular and epididymal sperm counts, and fertility. Despite these effects, serum T, LH, FSH, and STF-T concentrations were not altered.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗