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PubMed2006

Sperm DNA damage: importance in the era of assisted reproduction.

PURPOSE OF REVIEW: With the proliferation of assisted reproductive technologies, there is an increasing awareness of the importance of sperm DNA damage. With the recent advent of in-vitro fertilization/intracytoplasmic sperm injection, we are bypassing the normal natural selection barriers and potentially introducing sperm with damaged DNA. To date, these consequences are still largely unknown. RECENT FINDINGS: Infertile men possess substantially more DNA-damaged sperm than fertile men, and this DNA damage may adversely affect reproductive outcomes. There may be a threshold level of DNA damage beyond which embryo development and subsequent pregnancy are impaired. Protamine deficiency and the effect of reactive oxygen species have been implicated in the etiology of sperm DNA damage. Assays of DNA damage are being used clinically to quantify objectively the degree of DNA damage in the sperm of infertile men in the hope of identifying more accurate ways of gauging fertility potential. SUMMARY: There now exists clinical evidence to show that sperm DNA damage is detrimental to reproductive outcomes. Tests for DNA damage may provide better prognostic information and may allow for better decision-making than standard semen parameters when evaluating the infertile couple. The etiology of the DNA damage and the full extent of the damage on reproductive outcomes need further study.

Chromatin↗

PubMed1997

Bioavailability and pharmacokinetics of intravenously and orally administered allopurinol in healthy beagles.

OBJECTIVES: To determine bioavailability and pharmacokinetic parameters for allopurinol and its active metabolite, oxypurinol. ANIMALS: 6 healthy, reproductively intact female Beagles, 4.9 to 5.2 years old, and weighing 9.5 to 11.5 kg. PROCEDURE: In the first part of the study, allopurinol was administered IV at a dosage of 10 mg/kg of body weight to 3 dogs and 5 mg/kg to 3 dogs; the sequence was then reversed. In the second part of the study, allopurinol was administered orally at a dosage of 15 mg/kg to 3 dogs and 7.5 mg/kg to 3 dogs; the sequence was then reversed. In the third part of the study, allopurinol was administered IV (10 mg/kg), orally (15 mg/kg) with food, and orally (15 mg/kg) without food. Plasma samples were obtained at timed intervals, and concentrations of allopurinol and oxypurinol were determined. RESULTS: Maximal plasma allopurinol concentration and area under plasma allopurinol and oxypurinol concentration-time curves were 2 times greater when dogs were given 10 mg of allopurinol/kg IV, compared with 5 mg/kg, and when dogs were given 15 mg of allopurinol/kg orally, compared with 7.5 mg/kg. Allopurinol elimination half-life, time to reach maximal plasma oxypurinol concentration, and oxypurinol elimination half-life were significantly greater when dogs received 10 mg of allopurinol/kg IV, compared with 5 mg/kg, and when dogs received 15 mg of allopurinol/kg orally, compared with 7.5 mg/kg. CONCLUSIONS: Elimination of allopurinol is dependent on nonlinear enzyme kinetics. The bioavailability of allopurinol, and pharmacokinetic parameters of allopurinol and oxypurinol after oral administration of allopurinol, are not affected by administration with food. CLINICAL RELEVANCE: A dose threshold exists beyond which additional allopurinol would not substantially further inhibit xanthine oxidase activity. Oral administration of > 15 mg of allopurinol/kg to dogs would not be expected to result in greater reduction of plasma and urine uric acid concentrations. Also, allopurinol may be administered to dogs for dissolution or prevention of urate uroliths without regard to time of feeding.

Administration, Oral↗

PubMed1998

Ofloxacin: the next generation of antibiotic in sperm and embryo cultures for assisted reproductive technologies.

OBJECTIVE: To analyze the effect of different concentrations of ofloxacin on sperm kinematic parameters and to determine the embryotoxicity of ofloxacin at physiologic and at 100x concentrations. DESIGN: Prospective comparative study. SETTING: Clinical and academic research environment. PATIENT(S): Pooled cryopreserved donor sperm (n = 7). INTERVENTION(S): Human sperm were processed through two-layer discontinuous Percoll gradients, and the resultant pellet was resuspended in either HEPES-buffered human tubal fluid medium containing different concentrations of ofloxacin or the control medium. After measuring the kinematic parameters, the percentages of apoptosis and viability were obtained. Next, the sperm DNA was extracted and polymerase chain reaction of beta-globin gene was performed followed by denaturing gradient gel electrophoresis. Mouse embryos recovered at the one-cell pronuclear or zygote stages were cultured in the presence or absence of ofloxacin up to the hatched blastocyst stage and differences in development were recorded. MAIN OUTCOME MEASURE(S): Sperm kinematic parameters, sperm beta-globin gene, and number of embryos reaching the hatched blastocyst stage. RESULT(S): The number of embryos exposed to control and physiologic ofloxacin concentrations showed comparable excellent growth. However, the 100x concentration significantly arrested development. Rates of sperm viability and apoptosis measured 48 hours after exposure to the above concentrations were not different from controls. No differences were noted in the sperm kinematic parameters of sperm exposed to ofloxacin concentrations (1x, 10x, and 100x) or control medium after 0, 4, and 48 hours of incubation. Denaturing gradient gel electrophoresis of beta-globin genes from DNA exposed to varying ofloxacin concentrations failed to show any point mutations. CONCLUSION(S): Ofloxacin was embryotoxic at pharmacologic concentrations (100x). At physiologic or higher concentrations, ofloxacin appears to be safe and does not affect sperm kinematic parameters when compared with controls. This may indicate that sperm motility parameters alone cannot be relied on to evaluate the effects of drugs on fertility and that in vitro embryologic studies are essential. Ofloxacin at any concentration did not alter the rates of sperm apoptosis or viability. Ofloxacin does not appear to be mutagenic as evidenced by the beta-globin gene analysis.

Analysis of Variance↗

PubMed1985

Cross-sectional study of semen parameters in a large group of normal Chinese men.

Testicular size, semen characteristics and serum reproductive hormone levels were studied in 1239 normal Chinese men. The mean testicular size of 17 ml in this group of subjects was similar to other reports in Orientals but was smaller than that reported in Caucasians. Semen volume, and the sperm count, motility and morphology were comparable to those described for Caucasian subjects. The cervical mucus penetration test (Kremer's test) and the zona-free hamster egg penetration test were also studied in some of the subjects. Age showed a positive correlation with the serum levels of FSH and LH, which were highly correlated with each other. Sperm concentration and the total sperm count were positively correlated with testicular volume, the length of abstinence, the % of sperm with an oval head, and the zona-free hamster egg penetration test, but were negatively correlated with serum FSH. Sperm motility was negatively correlated with the duration of abstinence but was positively correlated with the % normal sperm. The results constitute a normal data base from Chinese men for comparison with studies in male infertility and fertility regulation.

Adult↗

PubMedDate not supplied

Comparison of a discontinuous Percoll gradient method versus a swim-up method: effects on sperm morphology and other semen parameters.

Increasing the proportion of motile and normal spermatozoa is an important objective for assisted reproductive procedures. The aim of this study was to compare the results of a Percoll and swim-up-method, especially on the sperm morphology. The Percoll technique gave a recovery rate of 81.3% of motile spermatozoa against a recovery rate of 28.98% for the swim-up technique. When the percentage of normal spermatozoa was also brought into calculation the recovery rate with the Percoll technique decreased to 62.03% and increased to 31.81% for the swim-up technique. This was due to a decrease in the resultant morphology of the Percoll technique to a median of 8.0% and an increase to 11.5% for the swim-up technique from a median of 10.5% of the original samples.

Centrifugation, Zonal↗

PubMedDate not supplied

Reproductive biology of the slender loris (Loris lydekkerianus lydekkerianus).

The slender loris (Loris lydekkerianus lydekkerianus), a nocturnal prosimian, was studied for 21 months in its natural habitat of scrub jungle in Dindigul, south India. Here we report on its reproductive biology. Identified and unidentified lorises were observed for a total of 2,656 h. Reproductive seasonality was seen, with births and oestrus observed to be highest in April-June and October-December. The mating system was promiscuous with 1 female mating successively with 3-4 males. A gestation period of 5.5 months and an inter-birth interval of 7 months were recorded. Adult females had a reproductive potential of 4 infants per year. The findings presented in this paper constitute the first information on the life history parameters of wild slender lorises.

Animals↗

PubMed2002

The influence of simultaneous whole body exposure to cigarette smoke and low-protein diet feeding on fertility, reproduction, and progeny of rats.

The aim of the present study was to evaluate the toxicological influence of different concentrations of tobacco smoke and low-protein diet on fertility, reproduction, and survival of offspring of Wistar female rats. We studied three generations, two litters in each. There were 192 animals in parent generation. Animals were exposed to three different concentrations of tobacco smoke that were reflected by the carbon monoxide (CO) concentration (500, 1000, and 1500 mg CO/m3 air) during 11 weeks (six before and two weeks during mating, and three weeks of pregnancy). Additionally, animals were divided into two subgroups that were fed normal or low-protein diet. In the present study, we concentrated on the indices describing the reproduction ability, fertility, and rearing of pups of mothers exposed to tobacco smoke. The parameters of newborns survival were estimated also. We concluded that neither tobacco smoke exposure nor the low-protein diet changed the duration of pregnancy. The tobacco smoke in all doses and low-protein diet had a negative influence on fertility, reproduction, and survival of newborns from exposed mothers. This influence was mainly attributed to the tobacco smoke exposure. The levels of carboxyhaemoglobin were increasing with increasing tobacco smoke concentration.

Administration, Inhalation↗

PubMed1988

[Assessment of the parameters of the growth kinetics of an experimental tumor].

A model of the Markov stochastic reproduction and death process is studied as applied to the analysis of time intervals necessary for the experimental tumours to achieve the fixed size. The analysis results have shown nonstationarity of the tumour growth processes during early stages of the tumour development. The presence of such a nonstationarity makes the experimental data interpretation difficult when applying the traditional approach to the tumour cell population kinetics.

Animals↗

PubMed1982

Genetic polymorphisms and human reproduction: a study of phosphoglucomutase in spontaneous abortion.

Theoretical arguments suggest that variation of metabolic parameters due to genetically determined enzyme polymorphisms may exert important effects on implantation and zygote development. The polymorphic enzyme phosphoglucomutase controlled by locus 1 (PGM1) is a phosphotransferase which plays a key role in carbohydrate metabolism and it is present in high concentrations in placental tissue. The enzyme has been studied in 47 couples with habitual abortion, in 36 women with single episodes of spontaneous abortion, in 48 women with induced abortion, and in control samples of normal individuals from the same population. Among couples with habitual abortion a significant increase of mean survival time of fetuses was observed in PGM1-heterozygote mothers as compared to homozygotes. An increased proportion of couples which may produce the hypothetical PGM1-null phenotype was also observed in habitual abortion, which suggests that homozygosity for PGM10 allele may contribute to fetal loss. Investigations on polymorphic enzymes involved in placental and fetal metabolism may contribute significantly to the problem of genetic etiology of spontaneous abortion.

Abortion, Habitual↗

PubMed1983

[Pathology among breeding does. Evolution of several plasma parameters among primiparous rabbit does].

One of the most important limiting factors of rabbit production is reproductive pathology. This pathology has two aspects: livestock reduction (elimination and death of rabbit does) and mortality of young rabbits before weaning. We studied alterations of hematocrit and of plasma Na, K, Ca, Mg, Pi, total proteins, prolactin, during gestation and lactation of primiparous rabbit does. In females which were going to die the first results showed a fall in plasma NaK, Ca concentrations and a rise in plasma Mg. We think that these alterations are only consequences of anterior metabolic alterations and are indicators or secondary causes of the animal's proximate death. We noticed a deep fall in plasma prolactin concentration before death; its signification is discussed. In the females which did not wean their whole litter, average prolacting levels during gestation and at the beginning of lactation were lower than in females weaning their whole litter. These first results would confirm the hypothesis that youngs' mortality is a pathology linked with dams' state.

Animal Diseases↗

PubMed1997

[Separation techniques ro achieve vital and reproduction competent equine spermatozoa populations--a survey].

Equine ejaculates are significantly characterized by widely varying parameters especially in those of practical relevance for equine Al. Therefore it is of interest for practical purposes to get subpopulations of concentrated, vital, and competent spermatozoa from the origin ejaculates. Special preparation of the donor stallions will stabilize sperm output. Fractionated semen collection from stallions supplies sperm enriched seminal fractions very useful to work with further in semen preservation. Most important to achieve a concentrated sperm subpopulation are semen manipulations post ejaculation represented conventionally in semen centrifugation. In the last decade alternative measurements have been introduced. Above all semen filtration using glasswool-sephadex and more recently membrane techniques gave good results indicating that these new techniques may replace semen centrifugation in the future. This article gives a survey of the different starting points and methods for separation of vital and concentrated sperm subpopulations of equine semen.

Animals↗

PubMed2005

Growth discrepancy in twins in the first trimester of pregnancy.

OBJECTIVE: The prevalence and significance of intertwin growth discrepancy in the first trimester of pregnancy are controversial. The aim of this study was to refine the incidence and outcome of this discrepancy in relation to dating of the pregnancy and other biometric parameters. METHODS: This prospective study of twin pregnancies initially evaluated at 11-14 weeks' gestation was conducted between 2001 and 2004. Differences in crown-rump length (CRL) and estimated gestational age (GA) were calculated for each twin pair and their distribution was analyzed according to chorionicity and mode of conception (spontaneous or following assisted reproductive technologies). CRL-based GA and actual GA were compared. Other biometric parameters were also compared for each twin pair. The distribution of discrepancies was analyzed according to pregnancy outcome. RESULTS: A total of 182 twin pregnancies was included. The mean+/-SD discrepancy in CRL was 3.4+/-3.18 mm or 5.1+/-4.69% and the 95th centile was 9.8 mm or 14.3%. There was no influence of chorionicity (P=0.44), mode of conception (P=0.18) and no relation with outcome (P=0.54). In conceptions resulting from assisted technology, the measured CRL of the smaller twin was closer to the actual GA. Cephalic and abdominal biometric measurements were significantly greater in the twin with the smaller CRL (P<0.05). The two cases with a discrepancy>15 mm were affected by trisomy 18 and triploidy, respectively. CONCLUSIONS: CRL discrepancy in twin pregnancies in the first trimester is a frequent finding. Discrepancy>95th centile indicates major growth delay of one twin, which could indicate the presence of aneuploidy. For milder degrees of discordance the CRL of the smaller fetus is a more accurate estimate of the actual GA.

Adult↗

PubMedDate not supplied

Reproductive hazards of lead exposure among urban Egyptian men.

Fifty-five urban Egyptian males, aged 20-40, were assigned to two main groups to study the effects of their exposure to lead (Pb). Group I, infertile men (INF, n = 30), was divided into environmentally exposed (INF-E, n = 15) and environmentally and occupationally exposed (INF-EO, n = 15). A matching group (II) of fertile men (F, n = 25) was divided into fertile, environmentally exposed (F-E, n = 10), which was the control group, and fertile, environmentally and occupationally exposed (F-EO, n = 15). Semen parameters (i.e., count, morphology, motility, and volume), blood and semen Pb levels, and reproductive hormonal indices (i.e., serum testosterone, FSH, and LH) were measured in all subjects. Lead levels were always higher in blood than semen. Semen lead levels were significantly higher in all groups vs. the control (F-E) group. While no changes were observed in testosterone levels across groups, variable effects on LH and FSH levels were observed. Infertile-EO subjects showed a definite pattern of impaired semen parameters in comparison with infertile-E. No abnormalities were detected in hematologic, hepatic or renal function.

Adult↗

PubMed2004

Limited pollen dispersal and biparental inbreeding in Symphonia globulifera in French Guiana.

In this paper, we report a study of the mating system and gene flow of Symphonia globulifera, a hermaphroditic, mainly bird-pollinated tree species with a large geographic distribution in the tropical Americas and Africa. Using three microsatellites, we analysed 534 seeds of 28 open pollinated families and 164 adults at the experimental site 'Paracou' in French Guiana. We observed, compared to other tropical tree species, relatively high values for the effective number of alleles. Significant spatial genetic structure was detected, with trees at distances up to 150 m more genetically similar than expected at random. We estimated parameters of the mating system and gene flow by using the mixed mating model and the TwoGener approach. The estimated multilocus outcrossing rate, tm, was 0.920. A significant level of biparental inbreeding and a high proportion of full-sibs were estimated for the 28 seed arrays. We estimated mean pollen dispersal distances between 27 and 53 m according to the dispersal models used. Although the adult population density of S. globulifera in Paracou was relatively high, the joint estimation of pollen dispersal and density of reproductive trees gave effective density estimates of 1.6 and 1.3 trees/ha. The parameters of the mating system and gene flow are discussed in the context of spatial genetic and demographic structures, flowering phenology and pollinator composition and behaviour.

French Guiana↗

PubMed1975

Reproductive capacity of the mentally retarded.

Ninety-seven mentally retarded females were studied to evaluate parameters of growth and development of secondary sex characteristics and the incidence of ovulation. These patients were selected on the basis of age and etiological classification. Patients were classified as Down's syndrome, brain damaged, or undifferentiated. The following parameters of growth and development were studied: anthropometric, bone age, and sexual maturation. Sexual maturation studies consisted of breast development, pubic hair, axillary hair, menarche, menstrual pattern, and ovulatory patterns. The following observations were made from this study: 1. Physical growth and secondary sexual development were retarded in all parameters. 2. The undifferentiated and brain damaged groups showed almost identical patterns of growth and development of secondary sexual characteristics. 3. The Down's syndrome group was the most retarded in physical growth and in secondary sexual development. 4. Skeletal age was a better guide than chronological age or height and body weight to the prediction of development of secondary sex characteristics and age at onset of menarche. 5. In 26 mentally retarded females who had achieved menarche the incidence of ovulation was approximately 60 percent.

Adolescent↗

PubMed2003

The effect of endometrial thickness on IVF/ICSI outcome.

BACKGROUND: During the menstrual cycle the endometrium undergoes cyclic proliferative and secretory changes in preparation for implantation. If this preparation is not sufficient, then implantation will fail. The impact of endometrial thickness on the day of embryo transfer on IVF outcome was investigated in the present study. METHODS: A retrospective analysis was conducted of 1228 IVF/ICSI cycles. Stimulation was with clomiphene citrate (CC) + hMG in one-third of the cycles, and ultrashort GnRH agonist stimulation in two-thirds. Cycle parameters were compared between pregnant and non-pregnant patients. A similar comparison was made between ongoing pregnancies and those that resulted in a loss. RESULTS: There were more follicles, oocytes and embryos, the endometrium was thicker and the embryo quality was higher among women who became pregnant when compared with non-pregnant women after assisted reproduction. The pregnancy rate improved as endometrial thickness increased. No difference in cycle parameters and endometrial thickness was found between ongoing pregnancies and pregnancies that resulted in a first-trimester loss. CC had no measurable adverse endometrial effect, but the pregnancy rate was lower in CC+hMG cycles. CONCLUSIONS: Increased endometrial thickness is associated with higher pregnancy rates. However, neither attainment of pregnancy nor pregnancy outcome was predicted by endometrial thickness alone.

Abortion, Spontaneous↗

PubMed1998

Effects of Great Lakes fish consumption on the immune system of Sprague-Dawley rats investigated during a two-generation reproductive study.

The effects of Great Lakes fish on food consumption, body and organ weights, and hematological parameters were investigated in the first- (F1) and second- (F2) generation Sprague-Dawley rats assigned to immunological studies. The parent- (F0) generation rats were fed either a control diet or diets containing 5 or 20% lyophilized chinook salmon from Credit River (Lake Ontario, LO) or Owen Sound (Lake Huron, LH). The F1 and F2 pups were exposed to the fish diet in utero, through the dam's milk to 21 days of age and through the respective diets to 13 weeks of age. The study included an F1-reversibility (F1-R) phase in which rats at 13 weeks of exposure to fish or control diets were switched to the control diet for 3 months. Statistically significant effects included increased growth rates in the F1 male rats fed the LH fish diets compared to those fed the LO fish diets; increased liver weights in the F2-generation male rats fed the LH-20% and LO-20% diets compared to those fed the 5% fish diets; reduced thymus weights in the F1-R female rats fed the LO-20% fish diet compared to those fed the LO-5% or LH-20% fish diets and in the F2 male rats fed the LO diets compared to those fed the LH diets; increased kidney weights in the F2 male rats fed the LH-20% diet compared to those fed the LH-5% or LO-20% diets; reduced but reversible effects on red blood cell (RBC), white blood cell (WBC), neutrophil, lymphocyte, and monocyte numbers in the F1-generation female rats fed the fish diets; reduced red blood cell (RBC), white blood cell (WBC), and lymphocyte numbers in the F2 male rats fed the LO diets compared to those fed the LH diets; and reduced WBC and lymphocyte numbers in the F2 female rats fed the LO-20% diet compared to those fed the LH-20% fish diet. These results suggested that long-term exposure to Great Lakes fish contaminants may have adverse effects on some immune-related parameters. The impact of such changes on the functional aspects of the immune system of rats and consequently on human health needs to be further investigated.

Animal Feed↗

PubMed1995

[Toxicology of reproduction and development. Changes in the male reproductive function caused by drugs and pollutants: potential effects on offspring].

Published clinical observations underline the difficulty of defining with epidemiological studies the effects that chemicals such as drugs, illicit substances environmental and workplace pollutants might have on the offspring through the male parent. The Authors highlight how defining this issue might help both guide preclinical research and evaluate correctly clinical observations which are often difficult to interpret based only on observations in the female parent. Clinical research already available shows that some chemicals are able to modify fertility by acting either at the neuroendocrine level or on the testis. However, it is more difficult to identify and quantify the potential damage to the offsprings during the different phases of pregnancy and postnatal life. Finally, the Authors discuss the parameters that should be considered to obtain an algorithm for evaluating the reproductive risk in males, along the lines of the risk for the embryo and fetus due to the use of drugs during pregnancy. Moreover, it is suggested that among the unwanted effects of drugs and pollutants, those related to the different components and phases of the male reproductive function be reported also in relation to the patient's age.

Environmental Pollutants↗