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H Boettger-Tong

Publications and source records attributed to H Boettger-Tong.

11 recordsLinked to original sources
PubMed2001

Trinucleotide (CAG) repeat polymorphisms in the androgen receptor gene: molecular markers of risk for male infertility.

OBJECTIVE: To determine whether changes in the polymorphic trinucleotide (CAG) tract of the androgen receptor gene are associated with spermatogenic defects in patients with male infertility. DESIGN: Case-control study of two ethnic groups. SETTING: University referral centers for male infertility at Baylor College of Medicine, Houston, Texas, and National University Hospital, Singapore. PARTICIPANT(S): Two hundred and fifteen patients with male infertility and depressed spermatogenesis and 142 fertile controls. MAIN OUTCOME MEASURE(S): Size of androgen receptor CAG alleles according to fluorescent-labeled polymerase chain reaction and automated analysis using Genescan software (PE Biosystems Asia, Singapore), and statistical examination of its relation to clinical variables. RESULT(S): In U.S. patients, the mean androgen receptor CAG length was significantly longer in infertile patients than in fertile controls (21.95 +/- 0.31 vs. 20.72 +/- 0.52). Logistic regression showed that each unit increase in CAG length was associated with a 20% increase in the odds of being azoospermic. The odds ratio for azoospermia was sevenfold higher for patients with > or =26 CAG repeats than in those with <26 CAG repeats. Although mean CAG length in Singapore patients was longer than in the U.S. samples, long androgen receptor CAG alleles were significantly related to male infertility in both populations. CONCLUSION(S): Long (> or =26) androgen receptor CAG alleles, which are found in up to 25% of azoospermic men, are associated with male infertility and defective spermatogenesis. Conception in these men is possible with assisted reproductive technologies, as many have spermatozoa in their testes.

Biopsy↗
PubMed2001

Testosterone inhibits spermatogonial differentiation in juvenile spermatogonial depletion mice.

The juvenile spermatogonial depletion (jsd) mutation results in spermatogonial arrest after the first wave of spermatogenesis. In homozygous jsd mice in a hybrid background (C3HxB6) that were identified with microsatellite markers, the percentage of tubules showing differentiating germ cells [tubule differentiation index (TDI)] rapidly decreased after 7 weeks of age with a correlative increase in the intratesticular testosterone (ITT) levels. Treatment with a GnRH antagonist, Cetrorelix, suppressed ITT and stimulated spermatogonial differentiation at the end of treatment. When treated mice were killed 5-13.3 weeks after the end of treatment, the ITT progressively increased, and the TDI progressively declined, but there was a transient appearance of tubules with mature spermatids. To delineate the role of testosterone (T) in spermatogonial arrest, we gave 7.6-week-old jsd mice exogenous T and/or the androgen receptor antagonist flutamide with or without GnRH antagonist for 4 weeks. Flutamide alone moderately stimulated spermatogonial differentiation (TDI = 30%). GnRH antagonist increased the TDI to 73%, and the addition of flutamide to the GnRH antagonist treatment further increased it to 95%. When T was combined with GnRH antagonist treatment, ITT was increased, and the TDI was reduced to 7%. Addition of flutamide to this combination reversed the T inhibition of GnRH antagonist stimulation of spermatogonial differentiation to a TDI of 57%. ITT levels showed a good negative correlation to the TDI obtained with various treatments, but no such correlation was observed for FSH or LH levels. The results indicate that T inhibits the ability of spermatogonia to differentiate in jsd mice through an androgen receptor-mediated process.

Androgen Antagonists↗
PubMed2000

Regulation of vascular endothelial growth factor expression by estrogens and progestins.

Estrogens increase the expression of vascular endothelial growth factor (VEGF) mRNA in the rodent uterus. This regulatory effect is rapid, beginning within 1 hr after hormone treatment, dose dependent, and blocked by the pure antiestrogen ICI 182,780. The induction of the transcript is blocked by inhibitors of RNA but not of protein synthesis, and we have recently identified estrogen response elements in the VEGF gene. Collectively, these findings indicate that estrogens regulate uterine VEGF expression at the transcriptional level via the classical nuclear estrogen receptor pathway. Estrogen induction of VEGF occurs in the stromal layer of the rodent uterus, and estradiol induces expression of VEGF transcript levels in cultured human uterine stromal cells. Progestins also induce VEGF expression in the rodent uterus, although the effect is less marked and slower in onset than estrogenic effects. The effect of progestins is blocked by the antiprogestin mifepristone (RU-486), suggesting that it is also mediated by a classical nuclear receptor pathway. In addition, progestins regulate expression of VEGF mRNA and protein in cultured human T47-D breast cancer cells. The development of uterine leiomyomas is associated with exposure to ovarian sex steroids, abnormal uterine bleeding is commonly seen in patients with leiomyomas, and fibroids require an increased vascular supply for their growth. These observations suggest that VEGF and other angiogenic factors may represent potential targets for the treatment and prevention of uterine fibroids.

Breast Neoplasms↗
PubMed1998

A murine TSPY.

Sequences homologous to human and bovine TSPY were isolated from M. musculus testicular cDNA, and a nearly full-length gene was polymerase chain reaction (PCR) amplified from mouse genomic DNA. This gene is apparently non-functional. Contrary to the situation encountered in species along the primate and artiodactyl lineages, in which TSPY is moderately repetitive, murine Tspy appears to be single copy. Murine Tspy is located on Yp, i.e. in the same syntenic group as in man. Sequence comparisons of murine, human and bovine TSPY exons suggest that TSPY became non-functional during rodent evolution.

Animals↗
PubMed1998

Evolution of the DAZ gene family suggests that Y-linked DAZ plays little, or a limited, role in spermatogenesis but underlines a recent African origin for human populations.

The recent transposition to the Y chromosome of the autosomal DAZL1 gene, potentially involved in germ cell development, created a unique opportunity to study the rate of Y chromosome evolution and assess the selective forces that may act upon such genes, and provided a new estimate of the male-to-female mutation rate (alpham). Two different Y-located DAZ sequences were observed in all Old World monkeys, apes and humans. Different DAZ copies originate from independent amplification events in each primate lineage. A comparison of autosomal DAZL1 and Y-linked DAZ intron sequences gave a new figure for male-to-female mutation rates of alpham = 4. It was found that human DAZ exons and introns are evolving at the same rate, implying neutral genetic drift and the absence of any functional selective pressures. We therefore hypothesize that Y-linked DAZ plays little, or a limited, role in human spermatogenesis. The two copies of DAZ in man appear to be due to a relatively recent duplication event (55 000-200 000 years). A worldwide survey of 67 men from five continents representing 19 distinct populations showed that most males have both DAZ variants. This implies a common origin for the Y chromosome consistent with a recent 'out of Africa' origin of the human race.

Africa↗
PubMed1998

A case of a laboratory animal feed with high estrogenic activity and its impact on in vivo responses to exogenously administered estrogens.

We recently noted that immature rats failed to exhibit a normal uterine response to exogenously administered estradiol as assessed by both biochemical (induction of gene expression) and morphological (altered uterine and vaginal histology and size) end points. An initial analysis suggested that this was due to a high degree of estrogenization from a dietary source which was producing a near maximal uterotrophic response prior to hormone treatment. Subsequent chemical analysis indicated that the feed in question contained high amounts of two well-known phytoestrogens, genistein (210 mg/kg) and daidzen (14 mg/kg), and the lot of feed in question produced a large uterotrophic effect when fed to immature ovariectomized rats. These findings illustrate that, despite increased awareness of phytoestrogens, some batches of animal feed contain very high amounts of estrogenic components which have marked effects on in vivo end points of hormone action. These observations have important implications for both basic research and screening methods that utilize in vivo approaches.

Animal Feed↗
PubMed1997

Cultured human uterine smooth muscle cells are retinoid responsive.

Primary cultures of human uterine smooth muscle cells have been widely used as a model system to evaluate agents that may play a role in the regulation of both normal and abnormal proliferative responses. We have used this in vitro system to determine if human uterine smooth muscle cells are responsive to treatment with a potent natural derivative of vitamin A, all-trans retinoic acid (ATRA). These studies were also designed to determine if there is a difference in retinoid responsiveness between normal smooth muscle and adjacent leiomyoma (a benign tumor of uterine smooth muscle). When cells were cultured in the presence of ATRA, a dose-dependent inhibition in proliferation was observed. This inhibition in proliferation was accompanied by an alteration in smooth muscle cell morphology. Both the inhibition in proliferation and the altered morphology were reversible when ATRA treatment was discontinued. Responsiveness to retinoids is determined, in part, by the expression of ligand-specific receptors belonging to the steroid/thyroid superfamily (RARs and RXRs); we have therefore identified the pattern of retinoid receptor transcript expression in human uterine smooth muscle cells. The data indicate that human uterine smooth muscle cells express retinoic acid receptors RAR alpha, beta, and gamma, and retinoid X receptors RXR alpha and beta. No difference in retinoid responsiveness or in the pattern of retinoid receptor expression was observed between normal smooth muscle and adjacent leiomyoma. This is the first observation of an antiproliferative effect of ATRA in uterine smooth muscle cells and the first report of retinoid receptor expression patterns in this cell type. Since retinoids are common pharmacologic tools in the treatment of a wide variety of hyperproliferative disorders, these observations may have both therapeutic and toxicologic implications.

Cell Division↗
PubMed1992

Competition between zonae pellucidae and a proteinase inhibitor for sperm binding.

Murine sperm bind a proteinase inhibitor of seminal vesicle origin at ejaculation. The inhibitor binds in the acrosomal region of the sperm head and is removed during in utero or in vitro incubation. Adding inhibitor to sperm reduces their ability to bind zonae, while adding the purified inhibitor binding site to cumulus-free, zona-intact oocytes reduces the ability of the oocytes to bind sperm. Immuno-aggregation of the inhibitor binding site results in exocytosis of the acrosome. These observations suggest that the inhibitor binding site may participate in zona binding and the acrosome reaction. If the inhibitor binding site binds both the zona and the seminal inhibitor, then these components should compete with each other for that site on the sperm. We show that purified seminal inhibitor, as well as other proteinase inhibitors, block zona-induced acrosome reactions. Likewise, zona glycopeptides block inhibitor/anti-inhibitor-induced acrosome reactions in a concentration-dependent fashion. The inhibitor/anti-inhibitor-induced acrosome reaction is sensitive to pertussis toxin and proteinase inhibitor and thus is similar to zona-induced reactions. These findings support the suggestion that the trypsin inhibitor binding site on the head of the sperm functions to insure sperm-zona binding and induction of the acrosome reaction.

Acrosome↗
PubMed1992

Role of monoclonal antibody J-23 in inducing acrosome reactions in capacitated mouse spermatozoa.

A monoclonal antibody (J-23) to the 15 kDa component on the sperm head, the acceptor, which functions in zona binding, was shown to induce the acrosome reaction in capacitated cells, but not in fresh cells. The antibody recognized its epitope in the acrosomal cap region of fresh spermatozoa and in the equatorial region on washed and capacitated spermatozoa. However, equatorial expression did not depend on the acrosome reaction, since washing fresh spermatozoa increased the percentage with equatorial fluorescence, but did not increase the percentage with reacted acrosomes. The data indicate that the acrosome reaction can be induced in capacitated spermatozoa in the absence of zona glycoproteins.

Acrosome↗
PubMed1991

Acrosome reaction induced by immunoaggregation of a proteinase inhibitor bound to the murine sperm head.

ZP3, a glycoprotein of the murine zona pellucida, functions both to bind acrosome intact sperm and to induce the acrosome reaction. Solubilized whole zonae as well as purified ZP3 are able to induce acrosome reactions in capacitated sperm. Pronase digests of whole zonae yield glycopeptides that bind to sperm but are unable to induce acrosome reactions. However, immunoaggregation of these glycopeptides results in the exocytosis of the acrosome in the majority of treated sperm. The data suggest that ZP3 triggers the acrosome reaction by the aggregation of ZP3 binding sites on the sperm head. If aggregation of ZP3 binding sites is important in the induction of the acrosome reaction, then it may be possible to induce the acrosome reaction in the absence of zona by immunoaggregation of the sites. This presentation deals with the immunoaggregation of a proteinase inhibitor of seminal vesicle origin (SVI) that binds to a site on the sperm head known to participate in zona binding. We show that capacitated murine sperm, pretreated with the SVI, will acrosome react, as determined by Coomassie brilliant blue staining, when incubated with rabbit antiinhibitor antiserum (anti-SVI). The percentage of SVI-treated sperm displaying an acrosome reaction is dependent on the concentration of the immune serum. Sperm stain positive for intact acrosomes when anti-SVI Fab fragments or normal rabbit serum is substituted for the immune serum. However, when capacitated sperm, treated with both SVI and anti-SVI Fab fragments, are incubated with goat antirabbit IgG, the majority of sperm acrosome react. The data suggest that the aggregation of SVI bound to the sperm surface, in the absence of zona glycoproteins, is sufficient to induce the acrosome reaction.

Acrosome↗