he central theme of our research is idiopathic or unexplained male infertility which affects about 1.5 million American men. For the present proposal we have identified a fertIle control population. and five groups of men with idiopathic male infertility: (a) Husbands of Infertile couples referred to our Sperm Physiology Laboratory (about 650 men/1000 samples per year); (b) Unexplained male infertility (already identified normospermic men with diminished sperm CK-M ratios); (c) Fertile and infertile patients with varicocele; (d) Husbands of 1300 infertile couples in which a detailed data base was developed, including their reproductive history. lifestyle, drug use and other epidemiological characteristics; and (e) Patients who receive medications that affect sperm function. In order to develop improved methods for the diagnosis and treatment of men with idiopathic infertility in the physician's office and in the Andrology laboratory we propose to study: 1) Sperm creatine kinase (CK) activity and CK-M isoform ratios, objective biochemical markers of sperm cellular maturity and fertilizing potential. Within this aim, we will: (a) Isolate the CK-M isoform of human sperm and will generate CK-M specific antibodies for the assessment of maturity rather than morphology of ejaculated sperm. (b) Develop sperm CK antibodies which will not react with seminal fluid CK, in order to directly measure sperm Ck in semen samples by immunotechnology already present in clinical laboratories and in doctors' offices. 2) In line with our hypothesis, which assumes that idiopathic infertility may be caused by isolated deficiencies of acrosome activation in mature sperm, and that in vitro enhancement of sperm function may correct this problem, we will (a) study the rate of both capacitation and acrosome reaction in fertile men and in men with idiopathic infertility; (b) study acrosome activation and the CK parameters in the same sample and (c) examine the possible correlation between sperm CK parameters and acrosome function in the paradigms of the hamster oocyte penetration assay and (ARIC). the Ca- ionophore mediated acrosome response test. 3) Following up on our discovery that hyaluronic acid increases sperm velocity, we will: (a) Study sperm velocity response in a hyaluronic acid """"""""challenge test""""""""; (b) Compare, in a kit available in doctors' offices, sperm progress In cervical mucus with and without hyaluronic acid; and (c) Develop hyaluronic acid beads for the selection of mature, viable sperm for intracytoplasmic injection. 4) Because idiopathic male infertility may arise due to various pathomechanisms, we will compare the diagnostic efficiency of sperm CK-parameters with """"""""strict"""""""" sperm morphology, with anilin blue staining, which probes sperm chromatin maturity, and with the hyaluronic acid velocity response test.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD032902-05
Application #
2889165
Study Section
Special Emphasis Panel (SRC (15))
Program Officer
Vogel, Donna L
Project Start
1995-05-05
Project End
2001-04-30
Budget Start
1999-05-01
Budget End
2001-04-30
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Yale University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
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Huszar, Gabor; Ozkavukcu, Sinan; Jakab, Attila et al. (2006) Hyaluronic acid binding ability of human sperm reflects cellular maturity and fertilizing potential: selection of sperm for intracytoplasmic sperm injection. Curr Opin Obstet Gynecol 18:260-7
Jakab Jr, Attila; Kovacs, Tamas; Kovanci, Ertug et al. (2003) [Numerical chromosome anomalies in human sperm at low sperm concentration] Orv Hetil 144:1473-80
Celik-Ozenci, Ciler; Catalanotti, Jillian; Jakab, Attila et al. (2003) Human sperm maintain their shape following decondensation and denaturation for fluorescent in situ hybridization: shape analysis and objective morphometry. Biol Reprod 69:1347-55
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Huszar, G; Stone, K; Dix, D et al. (2000) Putative creatine kinase M-isoform in human sperm is identifiedas the 70-kilodalton heat shock protein HspA2. Biol Reprod 63:925-32
Gergely, A; Kovanci, E; Senturk, L et al. (1999) Morphometric assessment of mature and diminished-maturity human spermatozoa: sperm regions that reflect differences in maturity. Hum Reprod 14:2007-14
Polcz, T E; Stronk, J; Xiong, C et al. (1998) Optimal utilization of cryopreserved human semen for assisted reproduction: recovery and maintenance of sperm motility and viability. J Assist Reprod Genet 15:504-12
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