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K van der Ven

Publications and source records attributed to K van der Ven.

At least 19 recordsLinked to original sources
PubMed2001

Association of soluble HLA-G plasma levels with HLA-G alleles.

Soluble HLA-G (sHLA-G) molecules are found in the peripheral blood of healthy females and males, in cord blood and in amniotic fluids and discussed to be a mediator in maternal-fetal tolerance. In this study we investigated whether there are allele-specific differences in expression of sHLA-G molecules. For this, the sHLA-G plasma concentrations of 94 healthy unrelated individuals were measured by ELISA and correlated to their HLA-G genotypes, as determined by sequence analysis of exon 2 and 3 of the HLA-G gene. Mean sHLA-G levels in individuals with the most common HLA-G alleles G*01011 (27.0+/-2.1 SEM ng/ml, n=66), G*01012 (28.4+/-3.2 SEM ng/ml, n=34) were very similar. In contrast, individuals carrying the HLA-G*01013 (8.1+/-1.7 SEM ng/ml, n=17) or the "null" allele HLA-G*0105N (8.2+/-3.2 SEM ng/ml, n=7) presented significantly (P(c)=0.001 and P(c)<0.01, resp.) reduced sHLA-G levels. Furthermore, individuals with the HLA-G*01041 allele had significantly (P(c)=0.004) increased sHLA-G levels (42.5+/-4.6 SEM ng/ml, n=14). These results demonstrate that the generation of sHLA-G molecules is associated to certain HLA-G alleles and imply that sHLA-G levels are under genetic control. As low and high sHLA-G plasma levels did not segregate with HLA haplotypes including the HLA-G*01013 or *01041 allele, additional mechanisms may be involved in the regulation of the individual sHLA-G levels. Nevertheless, the existence of "low" and "high secretor" HLA-G alleles further suggests different levels of functionality in immune regulation.

Alleles↗
PubMed2001

The HLA-G genotype is potentially associated with idiopathic recurrent spontaneous abortion.

The causes for recurrent spontaneous abortion (RSA) remain unknown in a large proportion of the cases. Human leukocyte antigen (HLA)-G and HLA-E are expressed on invasive trophoblast cells, and are supposed to confer to materno-fetal tolerance. A total of 14 different nucleotide sequences have been described for HLA-G, including one dysfunctional null allele (HLA-G*0105N), while five different sequences have been described for HLA-E. In this study, 78 RSA couples and 52 fertile controls were typed for HLA-G and HLA-E by direct sequencing or single strand conformational polymorphism (SSCP) respectively. The overall analysis showed no significant difference in allele frequencies for either HLA-G or HLA-E between the two groups. However, HLA-G allele frequencies in women who had suffered from five or more RSA differed significantly from fertile controls (P: = 0.001), and from women who had undergone three or four RSA (P: = 0.027). Detailed analysis demonstrated a significant increase in the proportion of the HLA-G alleles *01013 and *0105N in the whole group of RSA women compared with fertile controls (P: = 0.007). When studying the prognostic value of HLA genotyping for pregnancy outcome (n = 41), 31 patients (76%) gave birth to a living child without performing immunotherapy. Seven out of 10 (70%) couples suffering from a further RSA carried the HLA-G*01013 or *0105N allele, compared with 10 out 31 (32%) couples giving birth (P: = 0.06). This study suggests that the HLA-G genotype may be a contributing factor in RSA.

Abortion, Habitual↗
PubMed2000

Soluble HLA levels in early pregnancy after in vitro fertilization.

Intact pregnancy can be interpreted as a state of maternal immunotolerance toward an haploidentical fetus. Soluble HLA (sHLA) molecules increase during episodes of allograft rejection and are discussed as candidates to modulate immune responses. We questioned whether after in vitro fertilization (IVF) the subsequent intact pregnancy, early abortion, or tubal pregnancy influence the courses sHLA serum levels. Therefore, serum samples of 65 IVF patients were assayed by ELISA for sHLA-I, sHLA-G, and sHLA-DR concentrations preovulatorily and after a positive HCG test weekly until the 9th gestational week (GW). In 20 patients experiencing an early abortion the preovulatory sHLA-G mean level of 25.9 +/- 3.9 SEM ng/ml and the share of 4.2 +/- 0.8 SEM % on total sHLA-I were significantly (p < 0.05) reduced compared to women with intact pregnancy. The same differences (p < 0.0001) were seen during the monitoring of sHLA-G and sHLA-I levels in intact pregnancy versus early abortion until 9th GW. Twin pregnancy revealed a drastically increase of sHLA-G levels from the 8th GW compared to singleton pregnancies. Further, individual sHLA-DR levels increased during intact pregnancy but decreased in the group of early abortion. With regard to sensitivity and specificity for pregnancy outcome sHLA quantitation reached similar weight as routine HCG determinations at GW 5. Especially women with preovulatory low sHLA-G levels appear to be on risk for early abortion after IVF.

Abortion, Spontaneous↗
PubMed2000

Combination of hypospadias and maldescended testis as cardinal symptoms in gonosomal chromosome aberrations.

Intersexual genitals or distinct hypospadias in combination with maldescended testis can be caused by endocrinological as well as chromosomal abnormalities. Even in early childhood such clinical findings require specific diagnostic procedures and subsequent treatment which is often invasive but has special importance as regards the early diagnosis of gonadal tumors. We present a child with cryptorchidism on the right, inguinal testis on the left and penoscrotal hypospadias. Cytogenetic analyses revealed a mosaic karyotype 45, X/46, X, idic (Yp) with unequal distribution of the mosaic in different tissues. In consequence of this chromosomal aberration the patient had mixed gonadal dysgenesis which is associated with an increased risk of tumor development in the aberrant gonads. The principles of pediatric, urological, cytogenetic and endocrinological diagnostics and the mode of data collection in the presented case are described and discussed. Furthermore, a protocol for preventive screening is presented, which combines urological and endocrinological investigations in males with malformations of the genito-urinary tract to minimize the risk of tumor development in the aberrant gonads.

Child, Preschool↗
PubMed2000

Evidence for major histocompatibility complex-mediated effects on spermatogenesis in humans.

Studies in fertile and infertile populations suggest an influence of genes of the major histocompatibility complex (MHC) on reproduction, although it remains unresolved if MHC-mediated effects on fertility are based on direct immunological or non-immunological effects of human leukocyte antigen (HLA) genes or rather on defects in MHC-associated non-HLA genes which affect gamete quality and embryonic development. We analysed allele frequencies for HLA class II loci DQA1, DQB1 and DRB1 and HLA class II haplotype frequencies in couples with tubal and andrological infertility who were treated with assisted reproductive techniques. Males with severe andrological infertility had significantly different allele frequencies for all three HLA loci when compared to males with normozoospermia, whereas no difference was found in the females. Differences in allele frequencies were stronger when only males whose partners achieved pregnancies after assisted reproduction treatment were compared. In those subgroups, we could also observe significant differences in three locus HLA class II haplotype frequencies. In summary, patients with male factor infertility differ in their HLA class II allele constitution from males with normozoospermia, which suggests that genes identical to or located in close vicinity to HLA class II genes may influence spermatogenesis and male gamete function.

Alleles↗
PubMed2000

Cytogenetic and andrological status and ICSI-results in couples with severe male factor infertility.

AIM: To pursue whether cytogenetic aberrations correlate with specific spermatological or hormonal abnormalities. METHODS: 305 infertile couples were investigated. All male partners were referred to a complete andrological work-up with physical examination, determination of hormones, HIV testing and semen analysis. Cytogenetic analysis was carried out in both partners by means of standard techniques using cultured lymphocytes from peripheral blood. RESULTS: Among the 305 couples, 10 men (3.2%) and 10 women (3.2%) showed constitutional chromosomal aberrations, including reciprocal translocations (n = 7), Robertsonian translocations (n = 3), inversions (n = 3), other structural aberrations (n = 4) and sex chromosome aberration (n = 3). In addition to the impaired sperm count in most of the patients, a tendency to an increased proportion of spermatozoa with acrosome defect was observed. CONCLUSION: Chromosomal aberrations may contribute to the low fertilization and pregnancy rates in the infertile couples.

Chromosome Aberrations↗
PubMed1999

Characterization of testicular mouse glucosamine 6-phosphate deaminase (GNPDA).

Mammalian glucosamine 6-phosphate deaminase (GNPDA) was first detected in hamster spermatozoa. To further elucidate its role, we have cloned mouse GNPDA and produced a polyclonal rabbit anti-GNPDA antibody. This antibody recognized a 33 kDa protein in soluble extracts from mouse brain, liver, kidney, muscle, ovary, testis and sperm. Immunofluorescent analysis of the localization of GNPDA in male reproductive tissue revealed its presence in spermatids and in spermatozoa. In spermatids, GNPDA localized close to the developing acrosome vesicle and in spermatozoa close to the acrosomal region. Following the induction of the acrosome reaction, GNPDA fluorescence in spermatozoa was either reduced or GNPDA was absent. These data suggest that GNPDA might play a role in the acrosome reaction.

Acrosome↗
PubMed1998

Laser-assisted microdissection of the zona pellucida facilitates polar body biopsy.

OBJECTIVE: To investigate whether polar body biopsy can be performed after laser microdissection of the zona pellucida (ZP). DESIGN: Mouse zygotes were allocated randomly to three groups. The zygotes were subjected to laser microdissection of the ZP and polar body biopsy (group 1), laser microdissection alone (group 2), or no treatment (group 3). SETTING: University-based IVF program. PATIENT(S): Animal study. INTERVENTION(S): A hole was drilled in the ZP of mouse zygotes using a 1.48-micron noncontact diode laser. A microneedle was inserted and the polar body was aspirated. MAIN OUTCOME MEASURE(S): The efficacy of polar body biopsy after laser microdissection of the ZP was evaluated. RESULT(S): The laser diode beam allowed for precise drilling of a 14- to 18-micron hole in the ZP. Polar bodies could be aspirated without damaging the zygote and did not disintegrate during the biopsy. Zygotes developed to blastocysts and underwent the same hatching as control zygotes. Lower hatching rates were observed in untreated zygotes. CONCLUSION(S): Laser microdissection of the ZP with a noncontact laser system facilitates subsequent polar body biopsy. The use of blunt-ended micropipettes greatly reduces the risk of damage to the zygote or the polar body. This procedure makes polar body biopsy more accurate and effective for preimplantation genetic diagnosis.

Animals↗
PubMed1998

HLA-G polymorphisms and allele frequencies in Caucasians.

HLA-G, a nonclassical class I MHC molecule, is uniquely expressed on extravillous cytotrophoblasts of the maternal-fetal interface and is suggested to be essential for establishment of maternal-fetal immune tolerance. Although the level of polymorphism in HLA-G has originally been considered low, number, nature and site of polymorphisms seem to vary between different ethnic populations. We investigated HLA-G polymorphisms in a population of German and Croatian origin by SSCP-analysis and direct sequencing as well as RFLP analysis for presence of the 1597delC mutation. HLA-A alleles associated with the different HLA-G alleles were determined by SSP PCR-typing. In Caucasians, HLA-G exhibits a low degree of polymorphism on the amino-acid level and only slightly higher variability on the nucleotide level. In 264 independent chromosomes, 4 HLA-G alleles on the level of amino acid polymorphisms and an additional 6 variations of nucleotide sequences could be identified. The null-allele G*0105N was present at an allele frequency of 2.3%, which is higher than initially suggested for Caucasians but lower than in Hispanics and African-Americans. Furthermore, some HLA-G alleles exhibit strong linkage disequilibrium with HLA-A.

Adult↗
PubMed1998

Increased frequency of congenital chromosomal aberrations in female partners of couples undergoing intracytoplasmic sperm injection.

We evaluated the frequency of congenital chromosomal aberrations in a sample of 305 couples included in an intracytoplasmic sperm injection (ICSI) programme. Twenty individuals (3.3%) with congenital chromosomal abnormalities could be identified. The following types of abnormalities were observed: reciprocal translocations (n = 7), Robertsonian translocations (n = 3), inversions (n = 3), other structural aberrations (n = 4) and sex chromosome aberrations (n = 3). The rate of chromosomally abnormal males (10/305, 3.3%) lay within the expected range for patients with reduced semen quality. Surprisingly, 50% (10/20) of all abnormal karyotypes were contributed by the female partner of ICSI patients. These data confirm the higher incidence of chromosomal aberrations in infertile populations as compared with the baseline population risk. Additionally, the data imply that in some cases of male factor infertility a hidden female chromosomal factor may be present, which cannot be identified by standard clinical evaluation. In conclusion, we recommend chromosomal analysis in both partners of couples undergoing ICSI treatment.

Adult↗
PubMed1998

HLA-G polymorphisms: ethnic differences and implications for potential molecule function.

PROBLEM: Human leukocyte antigen (HLA)-G is uniquely expressed on extravillous cytotrophoblasts of the placenta and is postulated to be a mediator of maternal immune tolerance. Although it was originally considered to be nonpolymorphic, variations of the HLA-G DNA sequence have been reported, and a limited number of HLA-G alleles been defined. METHOD OF STUDY: The HLA-G wild-type sequence was compared with HLA-A2 with regard to the conservation of functionally essential parts of classical HLA-I molecules. HLA-G polymorphisms were analyzed under the aspect of ethnic differences, site, and consequences for postulated molecule functions. RESULTS: HLA-G exhibits a high degree of conservation relative to HLA-A2 in functionally relevant sites of HLA-class I molecules. However, polymorphic sites in HLA-G and classical HLA loci are not congruent. CONCLUSION: The type and localization of HLA-G polymorphisms suggest that different parts of HLA-G molecule underlie different selective constraints.

Ethnicity↗
PubMed1997

Success of intracytoplasmic sperm injection in couples with male and/or female chromosome aberrations.

This paper reports on results of intracytoplasmic sperm injection (ICSI) in patients in whom constitutional or secondary chromosome aberrations were detected in the male and/or female partner. Out of 434 couples treated by ICSI (590 cycles), 16 couples (3.7%) were affected by constitutional chromosome aberrations and 96 (22.1%) by secondary chromosome aberrations. Constitutional chromosome aberrations were found in eight male and eight female patients. Couples with the aberration in the male showed significantly lower fertilization, implantation and pregnancy rates (P < 0.05). The occurrence of female constitutional chromosome aberrations led to lower fertilization rates but implantation and pregnancy rates were similar to a control group; however, a higher abortion rate was noted. In the group with secondary chromosome aberrations, 22 males and 59 females carried an abnormality and in 15 couples, both partners. Compared to the remaining (unaffected) 322 couples, fertilization and embryo transfer rates were reduced but implantation rates and pregnancy rates were not different. In all couples where an abortion occurred, mainly parental autosomal aberrations were involved (six out of eight). Our retrospective analysis shows that an unexpectedly high number of infertile couples in an ICSI programme are affected by chromosome aberrations, which in turn may explain the reduced fertilization rates observed in this subgroup of patients.

Abortion, Spontaneous↗
PubMed1997

Combined cytogenetic and Y chromosome microdeletion screening in males undergoing intracytoplasmic sperm injection.

We evaluated the frequency of chromosomal aberrations and microdeletions of the Y chromosome in a sample of 204 patients included in an intracytoplasmic sperm injection (ICSI) programme. The prevalence of Y chromosome deletions in males with severely or only moderately reduced sparm counts is mainly unknown, so that patients were chosen with sperm counts ranging from mild oligozoospermia to azoospermia. While six out of 158 (3.8%) patients showed constitutional chromosomal aberrations, only two out of 204 (0.98%) patients were diagnosed with a microdeletion of Yq11. One had a terminal deletion in subinterval 6 of Yq11.23 which included the DAZ gene and a corresponding sperm count < 0.1 x 10(6) spermatozoa/ml. The second patient had an isolated deletion of marker Y6PH54c, a more proximal site in subinterval 5 on Yq11.23, but repeatedly showed sperm counts of 3-8 x 10(8) spermatozoa/ml. Thus, of the 158 patients who underwent a combined cytogenetic and Y-microdeletion screening, eight patients (5.1%) showed chromosomal abnormalities, either at the cytogenatic (n = 6) or the molecular level (n = 2). In conclusion, although rare in number, microdeletions of the Y chromosome can also be observed in patients with moderately reduced sperm counts. A more proximal site of the deletion breakpoint does not necessarily imply a more severe impairment of spermatogenesis than a distal deletion site. In our sample, the overall frequency of constitutional chromosomal aberrations exceeded the incidence of microdeletions of the Y chromosome even in patients with idiopathic azoo- or severe oligozoospermia.

Chromosome Deletion↗
PubMed1996

Population genetic studies of HLA-G: allele frequencies and linkage disequilibrium with HLA-A1.

HLA-G is a class I gene that is expressed in the extravillous cytotrophoblast. Although the function of this gene is still unknown, its expression at the maternal-fetal interface suggests that HLA-G may play a key role in the induction of tolerance during pregnancy. Preliminary to our studies of the effects of HLA-G polymorphisms on pregnancy outcome, we have defined HLA-G alleles in the Hutterites. We report here the presence of nine HLA-G alleles that differ with respect to nucleotide sequences, including four groups of alleles that differ with respect to amino acid sequences, and striking linkage disequilibrium between HLA-G and HLA-A alleles. The levels and sites of polymorphism in HLA-G suggest that this gene had a unique evolutionary history and may perform nonclassical functions at the maternal-fetal interface.

Adult↗
PubMed1996

Cystic fibrosis mutation screening in healthy men with reduced sperm quality.

The majority of men with cystic fibrosis (CF) are infertile due to a bilateral congenital absence of the vas deferens (CBAVD). However, clinically affected CF patients present a spectrum of genital phenotypes ranging from normal fertility to severely impaired spermatogenesis and CBAVD. Recently, it has become apparent that CF can manifest itself as isolated CBAVD in the absence of other clinical symptoms. The present study was undertaken to test the possible involvement of the CF gene in the aetiology of male infertility other than CBAVD. Semen specimens from 127 unrelated healthy males with various diagnoses of reduced sperm quality were screened for a panel of 13 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Fourteen of 80 (17.5%) healthy men with infertility due to reduced sperm quality and 3 of 21 (14.3%) men with azoospermia had at least one CF mutation (one azoospermic male was a compound heterozygote). The frequency of mutations in our sample of infertile males was significantly higher than the expected CF carrier frequency in the local population (P = 0.00139). No mutations were found in a control group of 26 individuals with normal semen parameters. This increased frequency of CF mutations in healthy men with reduced sperm quality and in men with azoospermia without CBAVD suggests that the CFTR protein may be involved in the process of spermatogenesis or sperm maturation apart from playing a critical role in the development of the epididymal glands and the vas deferens.

Case-Control Studies↗
PubMed1995

HLA-DQA1 and HLA-DQB1 haplotypes in aborted fetuses and couples with recurrent spontaneous abortion.

HLA haplotypes may be associated with spontaneous abortion through a variety of mechanisms, including maternal hyporesponsiveness to fetal alloantigens, maternal autoimmunity, and HLA-linked t-locus homologues. HLA-DQA1 and HLA-DQB1 haplotypes were determined in 37 couples with a history of recurrent spontaneous abortion (RSAB), 40 of their abortuses, and 20 fertile control couples. The distribution of haplotype frequencies did not differ between control subjects and RSAB wives, RSAB husbands, or abortuses. The frequency of the HLA-DR5-linked haplotype, DQA1*501/DQB1*301, which was considered a marker for immune hyporesponsiveness, did not differ between RSAB wives and control subjects (P = 0.353). The frequency of the autoimmune-associated HLA-DR3-linked haplotype, DQA1*0501/DQB1*0201, did not differ significantly between RSAB wives and control subjects (P = 0.103). The frequency of the DQA1*0201/DQB1*0201 haplotype in RSAB husbands was greater than the 95th percentile confidence limit of the frequency of this haplotype in control subjects. Among seven RSAB husbands who were heterozygous for this haplotype and did not share a DQA1*0201 allele with his wife, the haplotype was transmitted to 6 of 7 abortuses (3.5 expected). Although the small size of this sample precludes drawing conclusions regarding HLA transmission biases in RSAB couples, these data have generated a specific hypothesis regarding the DQA1*0201/DQB1*0201 haplotype that can be investigated in future studies.

Abortion, Habitual↗
PubMed1994

HLA-G polymorphisms in African Americans.

HLA-G is a class I MHC gene most notable for its restricted tissue distribution. The unique expression of this gene in extravillous cytotrophoblast at the maternal-fetal interface suggests that HLA-G plays a critical role in human pregnancy. Previous studies have reported that HLA-G has a limited repertoire of rare alleles, unlike the classical class I alleles, which are among the most polymorphic human genes. To determine the full extent of sequence variation in this gene, we examined the nucleotide variation in the first six exons of this gene in 45 healthy African American persons. By using sensitive techniques that detect > 95% of nucleotide substitutions, we detected two sequence variations in the alpha-1 domain (exon 2) and 24 sequence variations in the alpha-2 domain (exon 3) that result in amino acid substitutions. These data indicate that HLA-G is potentially capable of presenting a wide variety of peptides and of eliciting an allogeneic response, similar to the classical class I HLA genes.

Adult↗