The acrosome reaction (AR) is a central event of mammalian fertilization involving the fusion and fenestration of sperm head membranes. The molecular events that initiate this exocytotic process are not completely understood. The goal of this research is to increase our knowledge of those events in human sperm. These studies will be carried out with an in vitro human sperm incubation system. My laboratory has found that progesterone, a steroid hormone present in follicular fluid and secreted by granulosa cells and cells of the cumulus oophorus, can initiate the human sperm AR by increasing sperm [Ca2+]. This is of particular interest because: 1) sperm have to pass through the cumulus extracellular matrix during in vivo human fertilization; 2) the [Ca2+] increase is so fast (< 1 min) that a sperm steroid surface receptor may be involved. These studies will include: 1) whether steroids increase [Ca2+] in the human sperm head; 2) determination of the steroid structure necessary for the increase in [Ca2+] and the AR; 3) experiments to help determine whether or not there is a plasma membrane steroid receptor; 4) investigation of the possible role of steroid inhibition of Na+, K+ -ATPase and [Ca2+ + Mg2+] -ATPase in increasing sperm head [Ca2+] and thereby the AR. Methods to be used include: in vitro incubation of human sperm, computerized fluorescence image analysis, transmission electron microscopy,immunofluorescent assay of the AR, HPLC, (45)Ca-efflux studies and ATPase assays with (32)P-substrate. It is hoped that these studies will result in a greater understanding of the molecular basis of human fertilization and thereby lead in the future to new methods of contraception and of treatment for infertility. In addition, the increasing of intracellular [Ca2+] by a steroid via a cell surface-mediated mechanism might have relevance to Ca2+-requiring events in somatic cells. Thus, these studies may also be of importance outside the field of fertilization.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD023098-05
Application #
2198764
Study Section
Reproductive Biology Study Section (REB)
Project Start
1990-08-01
Project End
1995-03-31
Budget Start
1994-04-01
Budget End
1995-03-31
Support Year
5
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of California Davis
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
Bray, Christopher; Son, Jung-Ho; Meizel, Stanley (2002) A nicotinic acetylcholine receptor is involved in the arosome reaction of human sperm initiated by recombinant human ZP3. Biol Reprod 67:782-8
Harrison, D A; Carr, D W; Meizel, S (2000) Involvement of protein kinase A and A kinase anchoring protein in the progesterone-initiated human sperm acrosome reaction. Biol Reprod 62:811-20
Buddhikot, M; Falkenstein, E; Wehling, M et al. (1999) Recognition of a human sperm surface protein involved in the progesterone-initiated acrosome reaction by antisera against an endomembrane progesterone binding protein from porcine liver. Mol Cell Endocrinol 158:187-93
Garcia, M A; Meizel, S (1999) Progesterone-mediated calcium influx and acrosome reaction of human spermatozoa: pharmacological investigation of T-type calcium channels. Biol Reprod 60:102-9
Garcia, M A; Meizel, S (1999) Determination of the steady-state intracellular chloride concentration in capacitated human spermatozoa. J Androl 20:88-93
Garcia, M A; Meizel, S (1999) Regulation of intracellular pH in capacitated human spermatozoa by a Na+/H+ exchanger. Mol Reprod Dev 52:189-95
Falkenstein, E; Heck, M; Gerdes, D et al. (1999) Specific progesterone binding to a membrane protein and related nongenomic effects on Ca2+-fluxes in sperm. Endocrinology 140:5999-6002
Meizel, S (1997) Amino acid neurotransmitter receptor/chloride channels of mammalian sperm and the acrosome reaction. Biol Reprod 56:569-74
Turner, K O; Syvanen, M; Meizel, S (1997) The human acrosome reaction is highly sensitive to inhibition by cyclodiene insecticides. J Androl 18:571-5
Meizel, S; Turner, K O; Nuccitelli, R (1997) Progesterone triggers a wave of increased free calcium during the human sperm acrosome reaction. Dev Biol 182:67-75

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