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Biomedical subjects

G Potashnik

Publications and source records attributed to G Potashnik.

87 records · Page 5Linked to original sources

Dibromochloropropane-induced reduction of the sex-ratio in man.

The present study evaluated the effect of paternal exposure to Dibromochloropropane (DBCP) during its production, on the sex ratio of offsprings conceived during the exposure period. The study population consisted of 30 families of which 13 fathers became azoospermic, 8 oligozoospermic and 9 normozoospermic. Of the 89 pregnancies recorded, 68 culminated in the birth of live infants. The prevalence of male infants conceived during the pre-exposure period was 52.9% , in contrast to 35.2% for boys conceived during exposure. For the combined azoospermic and oligozoospermic groups, a significantly low prevalence of male infants of 16.6% (p less than 0.025) was found. It is concluded that paternal exposure to DBCP during its production process is associated with a significant decrease in the sex ratio of offsprings conceived during the exposure period. This drop in the sex ratio might be a reflection of the early effect of DBCP on male reproductive performance before a state of severe testicular dysfunction and infertility is reached.

Antinematodal Agents↗

Chromosomal analysis and health status of children conceived to men during or following dibromochloropropane-induced spermatogenic suppression.

Although the mutagenic effect of Dibromochloropropane (DBCP) on experimental mammal systems has been described, its possible effect on the human genome has not yet been investigated. The present study describes the results of chromosomal analysis and health evaluation of offspring conceived to families during and after paternal exposure to DBCP. Ten children conceived during or following severe exposure and four who were conceived prior to DBCP exposure were evaluated. The chromosomal constitution of peripheral lymphocytes was normal in all cases. The mode of delivery, birth weight, physical examination and growth pattern were normal. No congenital malformations were detected. One spontaneous abortion out of 23 pregnancies was recorded. These results suggest that paternal exposure to DBCP, severe enough to cause azoospermia or oligozoospermia did not alter the paternal sperm genome or the chromosomal constitution of offspring conceived during or after exposure. This is further supported by the excellent health and lack of malformations among the children, along with the low rate of spontaneous abortions in the families studied.

Adolescent↗

Chromosomal rearrangements in three infertile men.

Three chromosomal rearrangements: a balanced reciprocal translocation, t(14;10) (q22;q13), a Y-autosome translocation, t(Y;16) (q11;p13) and a deleted Y chromosome, Yq- were detected among 100 infertile men. The autosomal translocation, associated with oligozoospermia was found to be familial with various effects on the female carriers and the proband's father. The patients with the chromosome Y abberations were found to be azoospermic and might have lost the genes necessary for normal spermatogenesis.

Adult↗

Testicular damage development in rats injected with dibromochloropropane (DBCP).

Dibromochloropropane (DBCP) is an effective nematocide which was shown to suppress spermatogenesis and cause infertility in men and rats exposed to the compound. These damages were described only after 6-8 weeks post injection. The present study was set to detect the early development of the testicular damages. Rats were injected s.c. with DBCP 50 mg/kg. Control animals were injected with the vehicle alone (DMSO). Groups of animals were sacrificed 24 h, 1, 2, 3 and 4 weeks post injection. Body weight of DBCP treated animals was reduced from the second week post injection. Organs' weights of the DBCP treated rats, corrected for differences in body weights, were similar to those of controls. Four weeks post injection testes and accessory gland weights were significantly reduced as compared with controls. Percentage of damaged tubules in the DBCP treated animals were elevated from 16.6 +/- 3.5 at the first day to 70.2 +/- 6.4 at the 4th weeks. Concomitantly with the advance of tubular damage was a reduction in epididymal sperm count in the DBCP treated rats. One week post injection histological changes were evident. These included multinucleated giant cells and tubules blocked with sperm granuloma. It seems that alterations of spermatogenesis appear earlyer and are already noticeable one week post injection.

Animals↗

The effect of dibromochloropropane (DBCP) on in vitro cyclic AMP levels and testosterone production in rat testes.

Adult male rats were injected s.c. once a week for 3 weeks with DBCP, 20 mg/kg BW. Animals were sacrified 20 weeks after last injection. Body and testes weights were recorded and testes were taken for standard histological preparation and for in vitro experiments. The in vitro experiments were carried out on testes slices (90-110 mg) incubated for 3 h with or without the addition of hCG to the incubation medium. Cyclic AMP content of the tissue as well as testosterone released into the incubation medium were determined. Testes weights of DBCP treated animals were 68% lower than that of controls. All semiferous tubules were damaged and shrunken, thus, their number per microscope field was 2.6 times that of controls. Cyclic AMP levels in testes slices were similar in both DBCP treated and controls. The addition of hCG stimulated cyclic AMP accumulation to a much higher level in the DBCP treated than in controls. When calculated per one pair of testes the content in unstimulated pair was more than twice that of DBCP treated. Stimulation of hCG increased both DBCP treated and controls to similar levels. Testosterone release into the medium by slices was higher in DBCP treated than in controls and so was also the increment due to hCG stimulation. Similar results were obtained when testosterone release was calculated per one pair of testes. It is suggested that since the major testicular compartment damaged by DBCP is the tubular one, the proportion of the interstitium per testicular unit weight is larger than in controls, thus, cyclic AMP content increment due to hCG stimulation is much higher.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Long term effects of dibromochloropropane (DBCP) on male rats' reproductive system.

Adult male rats were injected s.c. once a week for 3 weeks with DBCP, 20 mg/kg B.W. Animals were sacrificed 5, 9, 13, 17, 25 and 50 weeks after last injection. Body weight was recorded once a week. Prior to sacrifice each male was presented with proestral females in order to determine the male's mating behaviour and fertility. Testes were removed, weighed and taken for standard histological examination. DBCP treatment caused a reduction of body weight which reverted back to control levels some 17 weeks post injection. Testes weights were reduced and remained low despite the recovery of body weight. Generally, all males showed normal mating behaviour but most of them were infertile. Testicular histology showed a correlation between decreasing testicular weight and increasing percentage of degenerated seminiferous tubules, which was on the other hand correlated with decreasing tubular diameter. Serum levels of FSH and LH were significantly increased in the infertile DBCP treated males while values for the fertile ones were similar to those of controls. There were no differences in serum testosterone levels between DBCP treated and control animals. It is concluded that in DBCP treated rats testicular degenerative damages are associated with increased circulating gonadotrophin levels and with normal testosterone levels. Although mating behaviour is unaffected fertility is depressed and does not recover for at least 50 weeks post injection. It is suggested that DBCP treatment affects mainly the activity of the Sertoli cells while the Leydig cells are affected to a much lesser degree.

Animals↗

Lack of birth defects among offspring conceived during or after paternal exposure to dibromochloropropane (DBCP).

The present study describes birth defects and health status of offspring of men with dibromochloropropane (DBCP) induced testicular dysfunction. One case with a major anomaly (urinary bladder extrophy and epispadias) and 2 cases of minor birth defects were observed among the 34 children evaluated. This rate was similar and not significantly different (p = 0.80) from that observed in a control group of 51 children conceived during pre-exposure in the same families. The health status of all the children was unremarkable. It is concluded that paternal exposure to DBCP, severe enough to cause azoospermia or oligozoospermia, did not increase the rate of congenital malformations or of impaired health status of offspring conceived during or after exposure.

Abnormalities, Drug-Induced↗

Ultrastructure of testicular cells in rats treated with dibromochloropropane (DBCP).

Three days after a single injection of rats with dibromochloropropane (DBCP) the testicular seminiferous tubules displayed focal damage, which became more pronounced six days after the treatment. Severely damaged tubules exhibited an almost complete exfoliation of the germ cells, while the Sertoli cells' lining remained mostly intact. The most affected germ cells were the spermatids. The mitochondrial sheath of the midpiece was often incomplete, vacuolated and/or broken into several pieces. In many cases the mitochondrial sheath protruded towards the interior, thus partially separating dense fibers 1, 2 and 9 from 3 to 8. In addition, cross sections revealed several midpieces of different flagellae surrounded by a single plasmalemma. In young spermatids, an atypical acrosome formation was noted concomitantly with a progressive emptying of the central nuclear region. This resulted in nuclei with electron lucent center surrounded by a chromatin belt. Sertoli cells displayed intense phagocytotic activity, their cytoplasm containing increased numbers of lysosomes, cellular debris and axonemal fragments.

Administration, Cutaneous↗

Age-dependent differences in the effects of 1,2-dibromo-3-chloropropane (DBCP) on fertility, sperm count, testicular histology and hormonal profile in rats.

This study was set up to determine if there are any age-dependent differences in the adverse effects of DBCP on the reproductive system of male rats. Groups of male rats were injected at the ages of 7,30 or 90 days with a single (50 mg kg-1 body weight) or repeated (20 mg kg-1 body weight once a week for 3 weeks) dose of DBCP, dissolved in DMSO. Ninety days after the last injection the males' fertility was estimated and the animals were killed. Blood was collected for future hormone assays, organs were weighed, testes were then taken for histological studies and sperm counts. The results were compared with those of control peers. The results showed that animals injected at the ages of 7 or 90 days under both regimens of treatment were adversely affected. The damage was noted in their fertility rate, sperm production, testicular histology and hormonal profile. Those injected at the age of 30 days showed only an insignificant variation compared with controls.

Age Factors↗

The effects of 1,2-dibromo-3-chloropropane (DBCP) on general toxicity and gonadotoxicity in rats.

This study was set to determine if there is a correlation between the general toxic effect and the gonadotoxic effect of DBCP on male rats. Groups of male rats were injected with a single dose of DBCP (50 mg kg-1) dissolved in dimethylsulfoxide (DMSO). Twenty four hours, one and four weeks post injection animals were sacrificed. Blood was collected for enzymes' and hormones' assays. Organs were weighed and testes were taken for histological examination and sperm counts. The results showed that DBCP at a dose of 50 mg kg-1 had a general toxic effect expressed by reduction in body and liver weights and reduced activities of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT). These changes show a tendency to revert to normal values with time. On the other hand, gonadotoxic effects increase in severity with time. The weight of testes and epididymides were reduced, sperm counts decreased and histological damage advanced, and FSH and LH blood levels increased 4 weeks post injection. It seems that in rats the gonadotoxic effect of DBCP is dissociated from the general toxic effects.

Alanine Transaminase↗

Ovarian stimulation concomitant with pituitary-ovarian axis suppression by different GnRH agonists.

The present study compared the effect of gonadotropin therapy alone with a combination of gonadotropins and GnRH agonist on ovarian stimulation in anovulatory women and in spontaneously ovulating patients in an IVF program. Nineteen infertile patients were treated with combined GnRH agonist/gonadotropin therapy for induction of ovulation. Ten women received combined therapy for ovarian stimulation in the framework of an IVF-ET program. Twenty-one additional patients served as controls, receiving gonadotropins but not GnRH agonist for induction of ovulation or ovarian stimulation stimulation before IVF-ET. This study indicates that the GnRH agonists Buserelin, Decapeptyl, and Decapeptyl CR are similarly effective in their ability to down-regulate pituitary-ovarian axis function. The suppressive effect occurred by 14 days in 77% of the patients, and never required more than 28 days. Stimulation of ovarian function, when carried out in the presence of a suppressed pituitary-ovarian axis, required an increased dose of exogenous gonadotropins (26.4 vs. 16.5 ampules). Our data do not support the view that GnRH analogs can aid in the synchronization process of oocyte maturation.

Anovulation↗

Specific IgG and IgA antibodies to Chlamydia trachomatis in infertile women.

IgG, IgA, and IgM antibody titers to Chlamydia trachomatis were determined in sera of 80 infertile women and 100 controls by a single antigen (L-2) immunoperoxidase assay. The infertile women included 50 with unexplained infertility and normal hysterosalpingogram (HSG) and 30 with abnormal HSG. The control sera included 50 from primiparous and 50 from multiparous women. The prevalence of C. trachomatis IgG antibody was significantly higher in infertile women with abnormal HSG as compared with infertile patients with normal HSG and controls (87% v. 20% and 10%, respectively). The geometric mean titer (GMT) of C. trachomatis IgG antibodies of infertile women with abnormal HSG was significantly higher than those of controls (20.7 v. 5.6). A significantly higher prevalence of C. trachomatis IgA antibodies was found in infertile women with both abnormal and normal HSG than in controls (77% and 14% v. 3% respectively). No C. trachomatis IgM antibodies (less than 2) were found in any of the infertile or control groups. The possibility that serum C. trachomatis IgA antibodies may serve as a marker for early recognition of persistent C. trachomatis is discussed.

Adult↗

Reproductive performance of dibromochloropropane-treated female rats.

Dibromochloropropane (DBCP) is an effective nematocide which has been shown to suppress spermatogenesis and cause infertility in both men and male rats. There are no similar reports concerning the effects of DBCP on female reproduction. The purpose of the present study was to attempt to interfere with the various phases of oogenesis. Proestral or pregnant rats were injected subcutaneously once with 40 mg/kg DBCP on one of each days of L12-L20 of gestation; a double dose (80 mg/kg) was injected in eight consecutive days (L11-L18). In addition, L13 fetuses were injected--directly into the amniotic sac--with 0.1 mg DBCP. Pooled data from the various days of gestation revealed that postimplantation losses were three times as high in the DBCP-treated animals as in DMSO-treated controls. Perinatal deaths were 58% higher and mean pup weights were 30% lower in the DBCP-treated rats than in controls. The reproductive performance of females exposed to DBCP while in utero was affected only to a limited degree (reduced number of ovulations and implantations) as compared with their DMSO counterparts. Doubling the dose (80 mg/kg) seriously reduced the birth weight of pups (50% of controls), all of which died within several hours post-partum. Direct injection of DBCP into embryos or to proestral rats did not have any adverse effects on their future reproductive performance. In contrast to the effect on spermatogenesis, it appears that oogenesis and ova are unaffected by DBCP.

Animals↗

Immunoperoxidase assay for detection of specific IgG and IgA antibodies to human spermatozoa in infertile women.

A new immunoperoxidase antibody-membrane antigen (IPAMA) technique for the detection of IgG and IgA antibodies specific for sperm antigens is described. The technique utilizes as antigen sperm cells dried on glass slides and stored at -70 degrees C. Sera of 82 infertile women, 50 primiparas, 50 multiparas and 25 children were tested by IPAMA. Results obtained with the IPAMA test for sperm-specific IgG are compared with the results obtained by the sperm immobilization test (SIT). By the IPAMA technique, 11 of 82 infertile women (13.4%) were positive for sperm-specific IgG antibodies, 12 (14.6%) for IgA antibodies and three (3.7%) for both. In the control groups only two of 125 subjects were positive for sperm-specific IgG and none for IgA antibodies. The difference in the prevalence of anti-sperm antibodies between the control groups and the infertility group was highly significant (P less than 0.001). There was agreement between the results of the IPAMA and SIT as to the presence or absence of antibodies in seven of the 11 IgG-positive sera in the infertility group. Four more sera were IgG positive by IPAMA only. The two positive sera in the control group were detected by both IPAMA and SIT. Since the IPAMA technique is simple, does not require special equipment and utilizes stored antigen, it seems that this method could be useful in mass screening of infertile couples.

Adult↗

Artificial insemination using fresh donor semen.

Four hundred and forty couples were treated by artificial insemination using fresh donor semen. The main indication was azoospermia. The overall pregnancy rate was 84.9% resulting in 287 take-home babies. The rate of ectopic pregnancies, perinatal deaths and spontaneous abortions were comparable to the general population. The accumulating pregnancy rate within 5 months was 86.8. Women older than 35 years had similar pregnancy rates than younger patients. Socioeconomic class, length of infertility and ovulatory disturbances either before or during treatment affected significantly the pregnancy rates.

Adult↗