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Biomedical subjects

L I Lipshultz

Publications and source records attributed to L I Lipshultz.

At least 109 records · Page 6Linked to original sources
PubMed1987

Medical treatment of male infertility.

After an appropriate clinical and laboratory assessment of a patient's fertility status, the clinician must often decide whether specific and empiric treatment is indicated. Specific treatment may take the form of replacement therapy (exogenous gonadotropins or GnRH) for pituitary or hypothalamic failure, inhibition of prolactin secretion, antimicrobial therapy, or immunosuppressive therapy for demonstrable immunologic infertility. Finally, ejaculatory dysfunction often requires sympathomimetic agents. Alternatively, in the normogonadotropic oligospermic patient, the major form of empiric therapy relies on the enhancement of physiologic hormone levels that influence spermatogenesis. Such "stimulation" therapy may be achieved by GnRH analogues, antiestrogens, exogenous gonadotropins, or androgens.

Autoimmune Diseases↗
PubMed1987

Functional tests of spermatozoa. Sperm penetration assay.

Optimization of each step in the standard protocol of the sperm penetration assay has increased the sensitivity of the traditional assay, and this increased sensitivity has allowed us to avoid the production of false-positive results. Development and use of routine quality control methods now enable us to compare different samples from a given individual and monitor with confidence biological variation and response to medical or surgical treatment. Although our test is extremely predictive of how well a patient's specimen may do as a result of normal intercourse, artificial insemination, and human in-vitro fertilization, it must be stressed that the sperm penetration assay and the sperm capacitation index reported by our laboratory only measure the ability of a sperm to capacitate and fuse with zona-free hamster ovum. How well spermatozoa disperse the cumulus and bind to and penetrate the human zona pellucida is not measured by this test. This would be reflected by an apparent "false-positive" outcome in the sperm penetration assay. However, our data from 138 patients suggest that this occurs only on rare occasions (in 2 of the 138). The test can be used only as a supplement to a conventional semen analysis because other factors, such as motile concentration and motility characteristics, clearly are also of importance particularly in vivo. The results obtained by our laboratory using the optimized assay described herein demonstrate that this test can play an important role in the evaluation of an infertile man.

Animals↗
PubMed1987

Testicular biopsy. Its use and limitations.

The need to distinguish ductal obstruction from ablative testicular pathology in the azoospermic patient is the primary indication for testis biopsy. Correct surgical technique and proper tissue processing are crucial to gaining the maximum amount of information from the biopsy specimen. The authors discuss the indications and techniques of testis biopsy and then review the major pathologic entities encountered clinically. Quantitative methods for describing the abnormal states of spermatogenesis are considered.

Adult↗
PubMed1986

Delta-9-tetrahydrocannabinol stimulates ABP secretion from rat Sertoli cells in vitro.

The effect of delta-9-tetrahydrocannabinol (THC) on rat Sertoli cell function was investigated. THC significantly increased ABP secretion by 1.5- to 2.1-fold but did not consistently enhance the stimulation of ABP induced by FSH, testosterone or dibutyryl cyclic AMP. ABP was measured by steady-state polyacrylamide gel electrophoresis, DEAE Bio-Gel and immunoassay; all three methods gave similar results. The minimal concentration of THC that stimulated ABP was 10 ng/ml; maximal stimulation was observed with 100-200 ng/ml. This effect was specific since THC did not affect gamma glutamyl transpeptidase activity or the secretion of plasminogen activator, lactate and transferrin. This observation that THC affects ABP secretion specifically is the first report of any differential effect of a drug on Sertoli cell secretion.

Androgen-Binding Protein↗
PubMed1986

In vitro fertilization in couples with male factor infertility.

The data from 83 consecutive in vitro fertilization-embryo transfer cycles were examined with emphasis on the presence of subfertile male parameters, including abnormal sperm density, motility, morphologic features, or an abnormal result in the sperm penetration assay (zona-free hamster ova penetration). There were 25 cycles (21 couples) in which there was a solitary or coexistent abnormal male factor. The presence of a male factor was associated with a lower fertilization rate and fewer embryos transferred. Statistically important reductions in the fertilization rate occurred with reduced sperm density and abnormal motility, but not with abnormal morphologic features. The parameter that was most significantly associated with human ova fertilizability was the ability to exceed two penetrations per egg in the sperm penetration assay.

Animals↗
PubMed1986

Predictive parameters of successful varicocele repair.

A total of 130 men presenting with oligospermia and clinically identifiable scrotal varicoceles was evaluated, treated surgically and followed for 1 year for pregnancy rate. The treatment outcome was compared to an age-matched cohort of 83 oligospermic men who had received empirical medical therapy with clomiphene citrate (25 mg. per day) for the same 1-year interval. This study was done to contrast treatment modalities in infertility and not as a strict control. Only eugonadotropic patients in both groups were used for comparison. In the varicocele group the over-all pregnancy rate was 38.5 per cent. Four variables (a lack of testicular atrophy, sperm density greater than 50 million per ejaculate, sperm motility 60 per cent or more and serum follicle-stimulating hormone values less than 300 ng. per ml.) proved to be accurate preoperative predictors of postoperative pregnancy success. Four other variables (varicocele size and laterality, sperm forward progression greater than 2 and normal sperm morphology 60 per cent or more) did not yield statistically significant rates of improvement in pregnancy postoperatively. The pregnancy rate of the eugonadotropic patients undergoing varicocele repair was 45.8 per cent. Despite statistical similarity in patient age, sperm density and mean gonadotropin levels the medically treated patients had a pregnancy rate of only 25.5 per cent, significantly lower than the surgically treated patients. In summary, patients with an identifiable varicocele had a greater chance of achieving a pregnancy following surgical correction than did those treated with empirical drug therapy. In addition, certain preoperative variables in the physical and laboratory analyses appeared to portend a greater surgical response.

Adult↗
PubMed1985

Rapid method for quantitation of androgen binding protein in Sertoli cell cultures and its use for measurement of binding kinetics.

The accurate measurement of the kinetics of binding of 5 alpha-dihydrotestosterone to the Sertoli cell specific protein, androgen binding protein (ABP), has been frustrated by the extremely rapid rate of dissociation of the ABP-dihydrotestosterone complex. We describe a rapid and highly sensitive assay suitable for ABP quantitation which utilizes DEAE Bio-Gel and [3H]dihydrotestosterone. The assay has been used to accurately measure the rate of dissociation (8.25 X 10(-4) s-1, t1/2 14 min) and the rate of association (2.04 X 10(5) M s-1) of the binding of [3H]dihydrotestosterone to rat ABP. The ratio of these rate constants is in perfect agreement with the equilibrium dissociation constant determined by Scatchard analysis (4.0 nM). This multipoint assay is extremely rapid such that binding can be measured at equilibrium, it has high precision (coefficient of variation 3%), and is particularly useful at low protein concentrations (50 ng/ml); furthermore, the assay background of nonspecific 3H-binding is extremely low (0.2%). Since at such low protein concentrations a 10 point Scatchard analysis can be performed on 1 ml culture medium containing as little as 3 fmol ABP, the assay is suitable for monitoring changes in ABP secretion resulting from manipulations of cells in culture. The assay which utilizes DEAE Bio-Gel A is compared to five alternative methods: the standard method of steady state gel electrophoresis, Dextran-coated charcoal assay, hydroxylapatite assay, DEAE filter assay, and radioimmunoassay. The DEAE Bio-Gel assay has advantages over all of these alternative methods. In summary, this new assay is particularly useful for monitoring temporal changes in the secretion of ABP, and the method is equally effective in quantitating ABP in rat, rabbit and hamster Sertoli cell cultures.

Adsorption↗
PubMed1985

Effect of aging and cold temperature storage of hamster ova as assessed in the sperm penetration assay.

The penetration of zona pellucida-free hamster ova by human spermatozoa has been used to quantitate sperm penetration potential. However, since mammalian eggs in vitro have limited viability, the effect of in vitro aging on the ability of hamster ova to be penetrated by human spermatozoa was examined. Zona-free ova maintained at room temperature (25 degrees C) lost their ability to be subsequently penetrated with a half-life of 50.1 +/- 8.8 minutes. This was partly the result of removing the zona pellucida by trypsin digestion, since zona-free oocytes in the presence of trypsin inhibitor or zona pellucida-intact oocytes had half-lives of 99.1 +/- 15.2 and 120.5 +/- 17.4 minutes, respectively. Reduction in penetration rates associated with ovum aging did not appear to be due to loss of viability and could be completely prevented by maintaining the ova on ice (4 degrees C). In the presence of TEST-yolk buffer at 4 degrees C, ova retained (100%) their ability to be penetrated for up to 24 hours and were morphologically indistinguishable from fresh ova. These observations show that ovum aging in vitro at 25 degrees C is much greater than previously anticipated. This may result in artifactually low and variable scores in the penetration bioassay.

Animals↗
PubMed1984

Conditions influencing human sperm capacitation and penetration of zona-free hamster ova.

The ability of human spermatozoa to penetrate zona-free hamster ova was examined following low-temperature capacitation (4 degrees C) in TES-Tris (TEST)-yolk buffer for periods of up to 66 hours. Results obtained from 66 individuals demonstrated that the number of penetrations per ova were increased by an average of 2.5-fold when spermatozoa were capacitated for 42 hours, as compared with 18 hours. Furthermore sperm with extremely poor penetration rates after 18-hour capacitation was often improved by longer capacitation periods. Patients from our infertility clinic with less than 20 X 10(6) spermatozoa/ml of ejaculate had significantly lower penetration rates when compared with patients and donors with greater than 20 X 10(6) spermatozoa/ml (P less than or equal to 0.001). The observed effects of TEST-yolk buffer appear to be related to its ability to preserve sperm motility over prolonged periods, during which increased capacitation of the total sperm population is achieved.

Animals↗
PubMed1984

Frequency of varicocele in black adolescents.

To determine the incidence of varicocele among blacks, 423 black adolescent males were examined. Fifty-eight (13.7%) had varicocele compared to a 14-15% incidence among white teenage males. The close to 10% of adolescents with a varicocele who develop subnormal fertility cannot be predicted, nor has it been shown that early varicocelectomy prevents the problem. There is a need for prospective evaluation of early varicocelectomy in adolescent males to determine if subnormal fertility can be avoided.

Adolescent↗
PubMed1984

Regulation of transferrin secretion by human Sertoli cells cultured in the presence or absence of human peritubular cells.

Transferrin represents 1-4% of the total proteins secreted by human Sertoli cells, and the amount secreted by the cells was maximal after a 4- to 5-day period in culture, the time chosen for each medium change. During this first 4- to 5-day period, the addition of FSH, insulin, (Bu)2cAMP, and isobutylmethylxanthine had no effect on transferrin secretion; however, from days 4-5 to 8-10, each of the above compounds significantly stimulated transferrin secretion compared to control values. Testosterone (in the absence or presence of insulin) had no effect. Transferrin secretion increased for the first 5 days in culture, with a similar magnitude in the presence or absence of the above stimulators, and thereafter declined, more so in untreated cultures. These results suggest that these agents do not stimulate, but, rather, limit the decline in transferrin secretion. When human peritubular cells were cocultured with Sertoli cells, transferrin secretion was significantly elevated compared to that by Sertoli cells alone. Interestingly, in the cocultures (Bu)2cAMP stimulated transferrin secretion when added for the first 4- to 5-day culture period. Human fibroblasts or spent medium from the peritubular cell cultures did not mimic the effect found when peritubular and Sertoli cells were cocultured. These results provide evidence that peritubular cells play a critical role in regulating human Sertoli cell function.

1-Methyl-3-isobutylxanthine↗
PubMed1984

Studies on human spermatozoa with round head syndrome.

The ability of spermatozoa with round head syndrome to penetrate zona pellucida-free hamster ova and to undergo nuclear decondensation was studied in three infertile patients. Whereas spermatozoa from pregnancy-proven donors bound to hamster ova and achieved a penetration rate of 100%, those with round heads did not bind to or penetrate any ova. While spermatozoa nuclear decondensation occurs after ovum penetration and indicates a positive result, it has now been demonstrated that this phenomenon can also be induced by incubating spermatozoa with crushed hamster ova. In addition, nuclei from normal and round-headed spermatozoa decondense in the presence of these ova to a similar degree. These observations suggest that infertility related to round head sperm morphology is associated with an inability to interact with and penetrate the oolemma, rathern than dysfunctional spermatozoan changes following penetration.

Animals↗
PubMed1983

Transferrin binds specifically to pachytene spermatocytes.

We have examined the secretion and binding of transferrin to rat testicular cells. The only testicular cells found to secrete transferrin were the Sertoli cells (control 549 +/- 6; FSH 1020 +/- 17 ng/day X 10(6) cells, mean +/- SEM). The Sertoli cells also contained specific binding sites for transferrin with a Kd of 2.0 X 10(-9)M. Of the other testicular cells examined only fractions rich in pachytene spermatocytes possessed specific transferrin-binding sites. Late pachytene spermatocytes (97% pure) bound [125I]iodotransferrin with a similar affinity as Sertoli cells (Kd 1.7 X 10(-9)M). Fractions of early and mid pachytene spermatocytes contained transferrin-binding sites with a higher affinity (Kd 0.3 X 10(-9)M). This is the first report of a protein that has specific binding sites on germ cells.

Animals↗
PubMed1983

Effect of cannabinoids on human Sertoli cell function in vitro.

Exposure to marijuana adversely affects spermatogenesis in humans and rodents. Since the Sertoli cell interfaces between changes in the serum hormonal milieu and the adluminal compartment and acts in various ways to support the germinal epithelium, this adverse marijuana mediated effect might be transmitted locally in the testes of humans by interference with Sertoli cell function. This report describes the effect of three active marijuana components: delta-9-tetrahydrocannabinol (THC), cannabidiol (CD) and cannabinol (CN) on various human Sertoli cell markers: transferrin, protein secretion and gamma glutamyl transpeptidase activity utilizing cultured human Sertoli cells. THC, CD, and CN tested in concentrations up to 200 ng/ml did not change transferrin secretion by these human Sertoli cells. Transferrin represents 1-4% of the total newly synthesized proteins of human Sertoli cells in culture. Even when the Sertoli cells were incubated for 30 days with THC there was no effect on transferrin secretion. The presence or absence of follicle-stimulating hormone, testosterone (T) or Fe3+ in the culture media did not modify the effect of THC. THC, CD, and CN also did not alter total protein secretion by Sertoli cells nor affect the level of gamma glutamyl transpeptidase activity.

Acyltransferases↗
PubMed1982

The effect of estrogen on Sertoli cell function.

This study describes the use of adult rats as a model to determine whether chronic estrogen treatment irreversibly alters the capacity of Sertoli cells to secrete androgen binding protein (ABP). Twenty-five adult rats were implanted with silastic tubing containing 17 beta-estradiol. After 1 month of estradiol the epididymides had regressed to 47 per cent of the weight of the epididymides in a control group. The amount of ABP in control epididymides was 9.9 fmol./mg. protein, whereas no ABP was detectable in those from rats treated with estradiol for 1 month. Serum testosterone levels had been depressed by 90 per cent. Estradiol treatment for 8 months resulted in a 60 per cent lower body weight and a 91 per cent decrease in testicular weight compared to control animals. During this period the epididymides regressed significantly. When Sertoli cells were cultured from the testes of the estradiol implanted rats, in spite of the dramatic changes which had occurred in the testes, within 4 days the cultured cells synthesized ABP in response to FSH and testosterone. Furthermore, the direct addition of estrogen at a concentration of 200 ng./ml. to rat Sertoli cell cultures failed to depress ABP below control levels. Thus, although estradiol depresses ABP synthesis in vivo, probably through its depression of both gonadotrophin secretion and testosterone biosynthesis, it has no direct effect on the Sertoli cells, and its long-term inhibition of ABP synthesis by an indirect mechanism is reversible.

Androgen-Binding Protein↗