Showing papers by "Christina Wang published in 2001"

Effects of transdermal testosterone gel on bone turnover markers and bone mineral density in hypogonadal men.

Abstract: OBJECTIVE Androgen replacement has been reported to increase bone mineral density (BMD) in hypogonadal men. We studied the effects of 6 months of treatment with a new transdermal testosterone (T) gel preparation on bone turnover markers and BMD. DESIGN This was a prospective, randomized, multicentre, parallel clinical trial where 227 hypogonadal men, mean age 51 years (range: 19–68 years) were studied in 16 academic and research institutions in the USA. Subjects were randomized to apply 1% T gel containing 50 or 100 mg T (delivering approximately 5–10 mg T/day) or two T patches (delivering 5 mg T/day) transdermally for 90 days. At day 91, depending on the serum T concentration, the T gel dose was adjusted upward or downward to 75 mg T/day until day 180. No dose adjustment occurred in the T patch group. MEASUREMENTS Serum T, free T and oestradiol, bone turnover markers and BMD were measured on days 0, 30, 90 and 180 before and after treatment. RESULTS Application of T gel 100 mg/day resulted in serum T concentrations 1·4 and 1·9-fold higher than in the T gel 50 mg/day and the T patch groups, respectively. Proportional increases occurred in serum oestradiol. Urine N-telopeptide/creatinine ratio, a marker for bone resorption, decreased significantly (P = 0·0019) only in the T gel 100 mg/day group. Serum bone osteoblastic activity markers (osteocalcin, procollagen and skeletal alkaline phosphatase) increased significantly during the first 90 days of treatment without intergroup differences but declined to baseline thereafter. BMD increased significantly both in the hip (+1·1 ± 0·3%) and spine (+2·2 ± 0·5%) only in the T gel 100 mg/day group (P = 0·0001). CONCLUSIONS Transdermal testosterone gel application for 6 months decreased bone resorption markers and increased osteoblastic activity markers for a short period, which resulted in a small but significant increase in BMD. Ongoing long-term studies should answer whether the observed increases in BMD are sustained or continue to be dependent on the dose of testosterone administered.

Semen quality and male reproductive health: the controversy about human sperm concentration decline

Abstract: Concern about the effect of environmental changes on male reproductive health has grown in recent years to become a major preoccupation in some developed countries A possible decline in human sperm concentration was suggested in the early seventies following studies in the US In 1992 a meta-analysis of 61 articles published by Carlsen et al concluded that the mean sperm count of healthy men had declined by 1% per year over the previous 50 years From 1995 and onwards, some retrospective, longitudinal analyses of the sperm count of fertile or infertile men contradicted this while others did not The demonstration of a geographical variation in sperm concentration, between and within countries or regions, appears to be less controversial The amplitude of the difference observed cannot only be explained by methodological or confounding factors, and must to some extent be attributed to ethnic, genetic or environmental factors As many of the published studies suffer from imprecision regarding the description of population characteristics and confounding factors, and were not designed with controlled and standardised methodology, the debate remains open Prospective studies in well-defined cohorts of men in various populations are required to evaluate the potential effect of external factors on male reproductive health These studies should not be limited to the analysis of sperm concentration, as this may not be the best biomarker of testis function and human fertility

Aging-Related Increased Expression of Inducible Nitric Oxide Synthase and Cytotoxicity Markers in Rat Hypothalamic Regions Associated with Male Reproductive Function

Abstract: We have previously demonstrated that the inducible nitric oxide synthase (iNOS) protein and total NOS activity increase in the hypothalamus and other regions of the male rat brain during aging. We hav

XXY male mice: an experimental model for Klinefelter syndrome.

Abstract: Klinefelter syndrome (47,XXY) is the most common sex chromosome aneuploidy in men. Thus, it is important to establish an experimental animal model to explore its underlying molecular mechanisms. Mice with a 41,XXY karyotype were produced by mating wild-type male mice with chimeric female mice carrying male embryonic stem cells. The objectives of the present study were to characterize the testicular phenotype of adult XXY mice and to examine the ontogeny of loss of germ cells in juvenile XXY mice. In the first experiment the testicular phenotypes of four adult XXY mice and four littermate controls (40,XY) were studied. XXY mice were identified by either Southern hybridization or karyotyping and were further confirmed by fluorescence in situ hybridization. The results showed that the testis weights of adult XXY mice (0.02 +/- 0.01 g) were dramatically decreased compared with those of the controls (0.11 +/- 0.01 g). Although no significant differences were apparent in plasma testosterone levels, the mean plasma LH and FSH levels were elevated in adult XXY mice compared with controls. The testicular histology of adult XXY mice showed small seminiferous tubules with varying degrees of intraepithelial vacuolization and a complete absence of germ cells. Hypertrophy and hyperplasia of Leydig cells were observed in the interstitium. Electron microscopic examination showed Sertoli cells containing scanty amounts of cytoplasm and irregular nuclei with prominent nucleoli. The junctional region between Sertoli cells appeared normal. In some tubules, nests of apparently degenerating Sertoli cells were found. In the second experiment the ontogeny of germ cell loss in juvenile XXY mice and their littermate controls was studied. Spermatogonia were found and appeared to be morphologically normal in juvenile XXY mice. Progressive loss of germ cells occurred within 10 days after birth. This resulted in the absence of germ cells in the adult XXY mice. We conclude that a progressive loss of germ cells occurring in early postnatal life results in the complete absence of germ cells in adult XXY mice. The XXY mouse provides an experimental model for its human XXY counterpart, Klinefelter syndrome.

Impairment of spermatogenesis in transgenic mice with selective overexpression of Bcl-2 in the somatic cells of the testis.

Abstract: To explore the functional role of Bcl-2 in germ cell development, transgenic mice carrying 6 kilobases of the inhibin-α promoter were generated to express human bcl-2 gene product in the gonads. Although female transgenic mice demonstrated decreased follicle apoptosis, enhanced folliculogenesis, and increased germ cell tumorigenesis, the adult males exhibited variable impairment of spermatogenesis. The degree of damage ranged from tubules with intraepithelial vacuoles of varying sizes to near atrophied tubules consisting of Sertoli cells and a few spermatogonia. Although there was no significant change in body weight, an approximately 34% decrease in testicular weights was noted in transgenic animals compared with wild-type mice. Gamete maturation, assessed by determining the percentage of tubules with advanced (steps 13–16) spermatids, was decreased to 44.4% of the values measured in the wild-type animals. The incidence of germ cell apoptosis increased 3.8-fold in the transgenic animals and was associated with a marked loss of germ cells. Electron microscopy of the testes further revealed large vacuoles in the Sertoli cell cytoplasm and dilations of the intracellular spaces between adjacent Sertoli cells, spermatid malformations, and increased germ cell apoptosis in the transgenic animals. There was no evidence of Sertoli cell death either by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay or electron microscopy. Leydig cell ultrastructure, cell size and numbers, and plasma levels of testosterone were not different between normal and the transgenic animals. Collectively, these results support the critical role of Bcl-2 in male germ cell development and are consistent with the gender-specific role of the Bcl-2 family members in reproduction.

Reproductive Technologies for Male Infertility

Abstract: The introduction of intracytoplasmic sperm injection (ICSI) in 1992 has revolutionized the treatment of male infertility (1) and has allowed couples whose only prior options were donor insemination to achieve pregnancies or adoption. Although in vitro fertilization (IVF) and related procedures have been used in the past for the treatment of male infertility, most assisted reproductive technology centers are using ICSI as the primary treatment for male infertility. Table 1 lists the cause of male factor infertility. Only a small minority of such patients are amenable to specific hormonal or pharmacologic therapy. Of these, the most probable candidates are the 1–2% of men with male infertility secondary to hypothalamic-pituitary (gonadotropin) insufficiency. These patients respond well to gonadotropin or GnRH therapy. Specific medical treatment is not available for most patients with testicular or idiopathic causes of male infertility. These patients are candidates for assisted reproductive technologies using oocytes from their spouses or partners. This article reviews the ICSI procedure, its indications, and techniques used to retrieve sperm and the risks and concerns that have been raised in regard to its safety, including the genetic risks to the fetus.