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The long-term effects of DDT exposure on semen, fertility, and sexual function of malaria vector-control workers in Limpopo Province, South Africa.

Hormonally active chemicals in the environment such as DDT have been associated with declining male reproductive health, especially semen quality. A cross-sectional study of 60 workers was performed near the Malaria Control Center (MCC) in Tzaneen, Limpopo Province, South Africa. Tests included a questionnaire (sexual function, fertility, and job history), a physical examination of the reproductive system, and semen analysis (produced via coitus interruptus or masturbation). Sperm count, density, and motility using the World Health Organization criteria and morphology using the strict Tygerberg criteria were determined. Serum o'p' and p'p' isomers of DDE, DDT, and DDD were measured. Forty-eight (81.0%) participants produced a semen sample, while all completed the questionnaires and physical examination. The mean sperm count was 93.8+/-130.3 million, and sperm density was 74.6+/-85.1 million/mL. The mean normal morphology score was 2.5+/-1.8% of subjects. Eighty-four percent of morphology scores were below either the WHO or the Tygerberg criteria, with the highest individual score being 6%. Self-perceived current problems with sexual function ranged between 10% and 20%. The most prevalent genital abnormality was abnormal testis disposition at 71%. There were few significant associations between DDT exposure measures (measured as years worked at MCC and serum DDT) and reproductive outcomes. p'p'-DDT was negatively associated with semen count (beta=-3.7+/-1.7; P=0.04; R2=0.05 adjusted for age, abstinence, physical abnormality, and fever in last 2 months). While the semen quality in the study was less than normal, no strong evidence for a DDT effect was found.

Animals↗

Testicular function in patients with testicular cancer treated with bleomycin-etoposide-carboplatin (BEC(90)) combination chemotherapy.

OBJECTIVE: To investigate the impact of bleomycin-etoposide-carboplatin combination chemotherapy on long-term fertility in patients with testicular germ cell tumors. METHODS: Twenty-five patients with high risk stage I and IM non-seminomatous germ cell tumors (NSGCT, Group A) and 44 with advanced seminoma or NSGCT (Group B) were treated with bleomycin 30 mg (days 2, 9, 16), etoposide 165 mg/m(2) (days 1-3) and carboplatin 400mg/m(2) or AUC 5 (day 1) (BEC(90)). Treatment was repeated every 3 weeks. Group A patients received 2 cycles of BEC(90), while Group B ones received 4 to 5 cycles of BEC(90). Sperm count and hormonal analyses were examined pre- and post-chemotherapy. Counts were classified as normospermia (NS) if >20 x 10(6)ml(-1), oligospermia (OS) if 1-20 x 10(6)ml(-1) and azoospermia (AS) if <1 x 10(6)ml(-1). RESULTS: Patients were followed for a median of 2.9 years post-chemotherapy. The post-orchidectomy median luteinizing hormone (LH) serum levels were slightly above the upper normal limit while the serum levels of follicle stimulating hormone (FSH) and testosterone (T) were within the reference interval. Thirty-eight (55%) patients had NS pre-chemotherapy. None of the 14 NS patients who received 2 cycles of BEC(90) had AS post-chemotherapy, while only 1 of the 24 NS patients who were treated with > or =4 cycles of BEC(90) had AS post-treatment. Among the NS patients, 93% and 83%, respectively, remained NS following chemotherapy. Overall, 90% of patients had recovery (61% NS, 29% OS) of spermatogenesis after treatment. The median FSH serum values were significantly elevated at least 1-year post-chemotherapy when compared with the pre-treatment levels. Eighteen months post-chemotherapy the median FSH values had returned to the reference limits. Serum LH and T levels were unaffected by treatment. The pre-treatment sperm count and the bulk of disease were significantly associated with recovery of spermatogenesis. No association was found between recovery of spermatogenesis and 2 or > or =4 cycles of chemotherapy, age > or =30 years and post-chemotherapy lymph node dissection. Thirteen patients (4 with OS) fathered 16 children. No congenital abnormalities occurred in any of these children. CONCLUSION: The BEC(90) regimen has no major effect on fertility and Leydig cell function. However, carboplatin-based chemotherapy has been proved less effective than cisplatin-based chemotherapy and is not currently used in the treatment of testicular cancer.

Adolescent↗

The varicocele and semen characteristics.

Our results indicate that the physical presence of a varicicele is not always associated with an alteration in sperm cell concentration and that a reduction of semen characteristics is more likely in men with reduced sperm counts. Our study also indicates that a higher pregnancy rate after varicocele ligation occurred in wives of patients in the lower sperm count groups. Other forms of therapy also were found to be associated with pregnancy in wives of men with varicoceles. The post-surgical pregnancy rate was 25 per cent compared to 12 per cent in the non-surgical group.

Cell Count↗

Sialic acid in human semen.

Sialic acid of seminal fluid of eighty two human subjects has been studied in relation to infertility. Normozoospermic group had highest sialic acid content (94 mgm/100 ml of the fluid) and was significantly different from other groups. The lowest sialic acid level was observed in necrozoospermic group (54 mgm/100 ml of the fluid). Azoospermic (62 mgm/100 ml) and vasectomised group (73 mgm/100 ml) had 33 and 22 percent less sialic acid level respectively than normozoospermic group. For the pooled observation sialic acid was found to be correlated (r = 0.282, significant at 5 percent level) with the total sperm count.

Fertility↗

Diminished decondensation and DNA synthesis in activated sperm from rats treated with cyclophosphamide.

Standard andrology tests do not predict fertility or assess the genetic quality of spermatozoa. To address these problems, we have analyzed sperm nuclear activation in vitro using cytoplasmic extracts of Xenopus laevis frog eggs. The objective of this study was to determine if rat sperm chemically damaged in vivo by cyclophosphamide treatment would respond abnormally in an in vitro rat sperm activation assay (RSAA). Male Sprague-Dawley rats were treated for 6 weeks with cyclophosphamide (CP) to induce DNA damage in post-meiotic germ cells. After the treatment period, cauda epididymal sperm were isolated, and incubated in cytoplasmic extracts of X. laevis frog eggs to induce chromatin decondensation and DNA synthesis in vitro. Sperm from treated rats displayed significant decreases in both decondensation and DNA synthesis when compared to sperm from control rats, consistent with the presence of CP-induced DNA crosslinks. No differences in body, testes, or epididymal weights were observed between control and treated rats, nor was sperm count diminished in the treatment group. These results demonstrate that the RSAA can be used to detect damaged sperm chromatin in the absence of detrimental effects on sperm count, and testis and epididymal weights.

Animals↗

Reversible inhibition of sperm production and gonadotrophin secretion in men following combined oral medroxyprogesterone acetate and percutaneous testosterone treatment.

Six men requesting male contraception received a daily oral dose of 20 mg medroxyprogesterone acetate (MPA) in combination with 50 or 100 mg percutaneous testosterone for 1 year. From the third month the sperm concentration was less than 10(6)/ml for all the men at one time or another during treatment, and usually less than 5 X 10(6)/ml, with an average reduction of 95% with respect to pre-treatment values. The sperm count returned to previous values 3-6 months after cessation of the treatment. While FSH and LH secretion was inhibited throughout the treatment period, plasma testosterone levels were not reduced. Oestradiol levels were unaffected while dihydrotestosterone was elevated. The secretory activity of the prostate and seminal vesicles was not appreciably affected; seminal carnitine concentration was reduced during the treatment with a subsequent return to pretreatment values. No pregnancies occurred during treatment. There was no impairment of libido in the subjects, nor any incidence of gynaecomastia, or increase in average body weight. The only observed metabolic side-effect was a moderate increase in glycaemia. A synergistic action of MPA and testosterone is proposed to explain the inhibition of gonadotrophin secretion.

Adult↗

Seasonal changes in semen quality and freezability in the Warmblood stallion.

The objective of this study was to investigate seasonal changes in stallion semen quality and to determine the best time for semen cryopreservation. Experiments were performed using 10 Warmblood stallions from the National Stud Farm in Avenches (Switzerland). Ejaculates were collected and frozen every other week during 1 year from January to December 1999. Volume, concentration, and motility, and the number of morphologically normal sperm and sperm with major defects (abnormal heads, acrosome defects, nuclear vacuoles, proximal droplets, abnormal midpieces) were evaluated. For all frozen-thawed semen samples motility as well as viability (SYBR-14/PI) was tested, and the hypoosmotic swelling test (HOS) was performed. To analyze seasonal differences 4 periods of 3 months each were defined: autumn (September, October, November), winter (December, January, February), spring (March, April, May) and summer (June, July, August). During the 1 year experiment all semen quality parameters showed a clear seasonal pattern. The volume, total sperm count and motility in fresh semen were significantly higher (P<0.05) in summer than in winter, while sperm concentration was significantly lower in summer compared to the other seasons. Regarding morphology, normal sperm was significantly lower (P<0.05) in summer than at any other time of the year and higher values (P<0.05) were found for major defects in summer than in spring and autumn. In frozen-thawed semen motility was significantly (P<0.05) improved in autumn when compared to spring and summer. Viability was lowest in summer and differed significantly (P<0.05) from other seasons. The HOS test revealed significantly more (P<0.05) membrane damaged spermatozoa in winter than in spring, summer and autumn. Our results demonstrate that in our climatic conditions clear seasonal differences occur in semen quality of fresh and frozen-thawed semen and that cryopreservation of stallion semen should preferably be performed in autumn.

Acrosome↗

[Male subfertility and conventional in vitro fertilization in Germany 1990 to 1993].

A retrospective study was carried out to compare the results of in vitro fertilisation (IVF) in 20936 patients with different sperm parameters who underwent IVF in Germany between 1990 and 1993. The study was designed to evaluate prognostic factors for IVF outcome, such as sperm parameters and pre-treatment diagnosis. The percentage of subfertile sperm parameters ( < 10 millions sperm per ml and/or < 30% progressive mobility and/or < 30% normal morphology) increased from 31.4% in 1990 to 51.1% in 1993. The fertilisation rate per puncture varied between 87.9% in patients with normozoospermia and 38.7% in patients with severe oligo-astheno-teratozoospermia (OAT). The fertilisation rate in patients with tubal indication was significantly higher than in patients with male indication and comparable spermatozoa. The pregnancy rate per embryo transfer was 23% in patients with normozoospermia and 13.8% in patients with "severe OAT syndrome" in the IVF semen parameters. On the other hand, patients with male sterility as pre-treatment diagnosis showed significantly higher chances of pregnancy than patients with a tubal factor (24% versus 20%, p < 0.05). Comparing percoll and swim-up preparation techniques, we found significantly higher fertilisation rates in normozoospermia and significantly higher pregnancy rates in subfertile patients after percoll sperm preparation. The results of the study demonstrated that patients with moderate subfertile sperm parameters have good chances of fertilisation and pregnancy following conventional IVE. It seems reasonable to set the boundary at a sperm count of 10 millions sperm/ml with 30% progressive motility and 30% normal morphology. Below these limits intracytoplasmic sperm injection shows better IVF outcome.

Adult↗

Insulin-like growth factor-I and alpha 2-macroglobulin in seminal plasma correlate with semen quality.

Insulin-like growth factor-I (IGF-I) and alpha 2-macroglobulin (alpha 2-M) are believed to be involved in the development of germ cells. IGF-I is mainly controlled by concentrations of human growth hormone (HGH), influences cell proliferation and differentiation and its action is mediated by insulin-like growth factor-binding proteins (IGFBP), placental protein 14 (PP14) and prostate-specific antigen (PSA). alpha 2-M acts as a broad spectrum proteinase inhibitor and a binding protein for many cytokines and hormones, e.g. inhibin and activin. This study was designed to identify concentrations of these molecules in seminal plasma in normal semen samples of healthy men, correlations with semen quality, the relationship of IGF-I and alpha 2-M with factors affecting male fertility, and whether vasectomy influences the concentrations of these molecules. Concentrations of IGF-I and alpha 2-M in human seminal plasma were related to semen quality, basal concentrations of HGH, testosterone, IGFBP-3, soluble fibronectin receptor (sFNR), PSA and PP14 in seminal plasma and to serum concentrations of luteinizing hormone (LH) and follicle stimulating hormone (FSH). Commercially available assays were used to analyse 69 semen samples of various quality and 11 post-vasectomy samples. IGF-I concentrations in seminal plasma were significantly correlated with the percentage of morphologically normal spermatozoa (r = 0.748, P = 0.00001) and sperm concentration (r = 0.301, P = 0.011), but negatively correlated with serum FSH (r = -0.506, P = 0.00006) and PSA in seminal plasma (r = -0.388, P = 0.00009). Total alpha 2-M was significantly correlated with sperm count (r = 0.423, P = 0.0005), percentage of progressively motile spermatozoa (r = 0.444, P = 0.00019), quality of motility (sperm motile efficiency, r = 802, P = 0.00001) and straight line velocity (r = 0.411, P = 0.0013). Correlation between the sperm concentration and HGH in seminal plasma was weak (r = 0.287, P = 0.015). Vasectomy reduced the concentration of total alpha 2-M (P = 0.00008) and HGH (P = 0.0068) in the seminal plasma; IGF-I was also reduced after vasectomy when the total ejaculate amount was considered. Thus IGF-I and alpha 2-M are significant for the germ cell development: IGF-I in the maturation of spermatozoa and alpha 2-M in progressive motility.

Follicle Stimulating Hormone↗

Effect of chronic administration of Tamoxifen on fertility in male bonnet monkeys (Macaca radiata).

Administration of Tamoxifen via the Alzet pump at a rate of 50 micrograms hr-1 for 90 days in the adult male bonnet monkeys Macaca radiata had no effect on the serum testosterone concentration determined at 10 AM and 10 PM as well as total sperm count determined at 15-day intervals over a period of 260 days. However, a significant reduction in sperm motility was observed beyond 90 days up until the 225th day. Breeding studies conducted from day 90 to 260 revealed that these males were infertile.

Animals↗

Factors affecting fertility after varicocelectomy.

We performed high ligation of the internal spermatic vein in 27 cases of left varicocele with disturbance of spermatogenesis, and studied postoperative fertility. The results indicated that the cases were divided into three groups, namely group I in which pregnancy occurred after ligation: group II in which the sperm count increased but no pregnancy occurred, and group III in which there was no improvement in the sperm count. The age, size of varicocele, preoperative volume of bilateral testicle, bilateral testicular histologies, serum LH, serum FSH, peak responded value after LH-RH administration, plasma testosterone and response after HCG administration were evaluated. We detected that the volume of bilateral testicles, bilateral testicular histologies, serum FSH and the response after LH-RH administration served as good indicators for postoperative evaluation of fertility.

Adult↗

Depressed semen quality: a study over two decades.

One hundred-eighty-five consecutive spermiograms from men of infertile couples in 1980-1981 were compared with as many spermiograms of age-matched controls from 1960-1961. The semen parameters analyzed were: volume, sperm density, and sperm morphology. The following significant changes were noted over the time period: the mean seminal volume decreased from 3.79 ml to 3.42 ml (p less than 0.05), the mean sperm count decreased from 125.4 mill/ml to 78.0 mill/ml (p less than 0.001) and the proportion of double sperm heads increased from 0.52% to 1.51% (p less than 0.001). Further analysis showed even more pronounced changes in these parameters for men living in the urban area compared those from the surrounding rural areas.

Adult↗

Improvement in sperm quality and function with French maritime pine tree bark extract.

OBJECTIVE: To determine the effects of Pycnogenol (French maritime pine tree bark extract) on sperm parameters and function in subfertile men. STUDY DESIGN: Prospective, nonrandomized, clinical study in a private infertility practice. Nineteen subfertile men were given 200 mg Pycnogenol daily orally for 90 days. Semen samples were analyzed before and after treatment for sperm count, motility score and strict morphology before and after capacitation, and mannose receptor binding. RESULTS: The mean sperm morphology following Ham's F-10 capacitation increased by 38% following Pycnogenol treatment, and the mannose receptor binding assay scores improved by 19%. CONCLUSION: Pycnogenol therapy resulted in improved capacitated sperm morphology and mannose receptor binding. The increase in morphologically and functionally normal sperm may allow couples diagnosed with teratozoospermia to forgo in vitro fertilization and either experience improved natural fertility or undergo less invasive and less expensive fertility-promoting procedures, such as intrauterine insemination.

Administration, Oral↗

A hypothesis on the declining dizygotic twinning rates in developed countries.

1) There has been an unexplained drop in dizygotic twinning rates during the past 15--20 years in all the developed countries for which data are available. In this note an explanation is offered for this decline. 2) There has been a decline in birth rates in almost all developed countries over much of the same period. 3) There is good evidence that in recent years there has been a decline in sperm counts--at any rate in the United States. 4) It is suggested here that this decline in sperm counts has been responsible for a decline in the probability that coitus in the fertile period will result in fertilization of the ovum. It is hypothesized that this decline is responsible for the decline in dizygotic twinning rates and--partially--for the decline in birth rates.

Birth Rate↗

Gestational and lactational exposure of male mice to diethylstilbestrol causes long-term effects on the testis, sperm fertilizing ability in vitro, and testicular gene expression.

The objective of the study was to determine the long-term effects of gestational and lactational exposure to diethylstilbestrol (DES; 0, 0.1, 1, and 10 microg/kg maternal body weight) on mouse testicular growth, epididymal sperm count, in vitro fertilizing ability, and testicular gene expression using cDNA microarrays and real-time PCR in mice on postnatal day (PND) 21, 105, and 315. In the high dose group there was a persistent decrease in the number of Sertoli cells, and sperm count was decreased on PND315 (P < 0.05). Sperm motion was unaffected; however, the in vitro fertilizing ability of epididymal sperm was decreased in the high dose group on both PND105 (P < 0.001) and PND315 (P < 0.05). Early and latent alterations in the expression of genes involved in estrogen signaling (estrogen receptor alpha), steroidogenesis (steroidogenic factor 1, 17alpha-hydroxylase/C17,20-lyase, P450 side chain cleavage, steroidogenic acute regulatory protein, and scavenger receptor class B1), lysosomal function (LGP85 and prosaposin), and regulation of testicular development (testicular receptor 2, inhibin/activin beta C, and Hoxa10) were confirmed by real-time PCR. The results demonstrate that early exposure to DES causes long-term adverse effects on testicular development and sperm function, and these effects are associated with changes in testicular gene expression, even long after the cessation of DES exposure.

Animals↗

Demonstration of the reversibility of spermatozoa suppression by testosterone oenanthate.

Long-term treatment with testosterone oenanthate in seven healthy young men was conducted with the aim of inducing reversible inhibition of spermatogenesis. During the observation period following discontinuation of the therapy spermatogenesis showed a gradual recovery. In three cases, however, the sperm counts did not reach pre-treatment levels. The subjects were re-examined 3 years after the start of the study, i.e. 2.5 years after the last injection of testosterone oenanthate. This examination confirmed that the testosterone treatment had had no recognizable negative influence on testicular function--on the contrary, in three cases analysis of the seminal fluid yielded higher sperm counts than previously.

Cell Count↗

Perfect anatomical reconstruction of vas deferens with a new microscopic surgical technique.

Early results with a new, two-layer microscopic technique for anastomosis of the vas deferens, using an operating microscope and ultrafine suture, reveal that patency of the vas deferens can be achieved in virtually every case. Normal sperm counts can be achieved in up to 95% of patients. Failure with conventional techniques is usually due to continuing partial obstruction. A poor sperm count after this technique is most likely due to an inherent inability of the patient to produce normal sperm, a likely sequela of chronic obstruction. Thus, while success is also good 10 years after vasectomy, it is not as predictable. Previous failure with a conventional operation does not limit success with a reoperation using the microscopic two-layer tehcnique. Operations on 200 patients since this original study are confirming these early results.

Antibodies↗

Flow cytometric analysis for sperm viability and counts in rats treated with trimethylphosphate or pyridoxine.

Six-week old SD-Slc male rats were treated for 4 weeks with compounds known to induce toxicological changes in male reproductive organs (pyridoxine in saline, 500 mg/kg/day, i.p.) or sperm (trimethylphosphate in distilled water, 100 mg/kg/day, p.o.). Each sperm sample taken from the cauda epididymis was analyzed with flow cytometry for the evaluation of sperm viability and counts. Sperm motility and morphology by microscopical observation, and histopathological examination of reproductive organs were also performed for estimating the adverse effects of each compound on spermatogenesis and sperm. While a decrease in sperm motility was noted for the trimethylphosphate group, the low motile sperm was evaluated as being viable sperm, not moribund, with flow cytometry. In the pyridoxine group, microscopical observation revealed morphological changes of sperm and a decrease of motility. The present sperm analysis with flow cytometry also suggested morphological changes reflected by dot plot as well as decrease of sperm viability and counts. These results indicated that this procedure led to profound findings in the compound-treated animals, with evaluation as viable sperm, not moribund, in a low motile sperm sample, and suggesting morphological changes in the dot plot of flow cytometry.

Animals↗