PubMed Health⌕ Search

Biomedical subjects

Arthur Leader

Publications and source records attributed to Arthur Leader.

6 recordsLinked to original sources

Exposure to trichloroethylene and its metabolites causes impairment of sperm fertilizing ability in mice.

Trichloroethylene (TCE) is a prevalent occupational and environmental contaminant that has been reported to cause a variety of toxic effects. Here, we have undertaken studies to test the hypothesis that TCE exposure adversely affects sperm function and fertilization. Sperm retrieved from mice exposed to TCE (1000 ppm) by inhalation for 1 to 6 weeks were incubated in vitro with eggs isolated from superovulated female mice. The number of sperm bound per egg was significantly decreased when mice were exposed to TCE for 2 and 6 weeks but not at exposures of 1 and 4 weeks. In vivo fertilization was also determined in superovulated female mice mated with males exposed to TCE for 2 to 6 weeks. The percentages of eggs fertilized, as assessed by the presence of two pronuclei, were significantly decreased after 2 and 6 weeks of TCE exposure. A slight but insignificant decrease was observed after 4 weeks of TCE exposure. The direct effects of TCE and its metabolites, chloral hydrate (CH) and trichloroethanol (TCOH), on in vitro sperm-egg binding were also investigated. Sperm-egg binding was significantly decreased when sperm were pretreated with CH (0.1-10 microg/mL). Significantly lower levels of sperm-egg binding were also detected with TCOH (0.1-10 microg/mL), although the decreases were not as pronounced as those for CH. These results showed that TCE exposure leads to impairment of sperm fertilizing ability, which may be attributed to TCE metabolites, CH, and TCOH.

Acrosome Reaction↗

Towards a more precise assay of sperm function in egg binding.

Historically, the treatment of severe male factor infertility has relied on donor sperm insemination. A decade ago the option of treating severe male factor infertility with partner sperm became a viable alternative. With the introduction of intracytoplasmic sperm injection (ICSI) in conjunction with in vitro fertilization (IVF), only men who produce no sperm are denied the option of fathering their own children. The use of ICSI has been extended to couples with mild male factors. Despite the known genetic risks (both inherent and de novo) of ICSI to offspring, couples with male factors as part of their infertility problem often prefer ICSI to standard IVF, due to apprehension that their sperm might not otherwise succeed in fertilization. This apprehension would be alleviated if an assay for the egg binding capability of human sperm were available. We examine here the possibility that recombinant human zona pellucida 3 (rec hZP3), the primary sperm receptor sulfoglycoprotein of the egg zona pellucida (ZP), be used as a human ZP surrogate for assessing sperm ability to bind to the ZP. Unlike human eggs, which cannot be obtained for this purpose, rec hZP3 can be produced in quantity. An efficient assay can be established by incubating sperm with rec hZP3 coated to a microwell plate. Infertile men with sperm having ability to bind to rec hZP3 can be advised to select standard IVF or intrauterine insemination, which have fewer genetic and medical risks.

Adult↗

Use of atomic force microscopy for morphological and morphometric analyses of acrosome intact and acrosome-reacted human sperm.

The objective of this study was to use atomic force microscopy (AFM), with submicron resolution, for morphophologic and morphometric analyses of acrosome intact and acrosome-reacted human sperm heads. A mixed population of acrosome intact and reacted sperm was produced by treating capacitated sperm with A23187, which induced the acrosome reaction in approximately 50% of total sperm population. This A23187-treated sperm suspension was then plated onto a coverslip and acrosome reacted sperm were preidentified by their specific staining with rhodamine-conjugated Concanavalin A. The sperm coverslip was then air-dried and scanned by a Nanoscope IIIa atomic force microscope, using the contact mode. Top and side view images processed through the illuminate mode revealed three dimensional sperm head contour, with the highest point situated in the head posterior in both acrosome intact and acrosome reacted sperm. Maximum height, length, and width measured in 50 acrosome intact and 50 acrosome-reacted sperm were the same in both populations. However, head length at half maximum height was significantly decreased in acrosome reacted sperm (2.99 +/- 0.24 microm vs. 3.56 +/- 0.32 microm of acrosome intact sperm), due to the sudden change of the height contour from the maximum peak to the anterior tip of acrosome-reacted sperm. Our results described here can therefore be used to differentiate acrosome intact and reacted sperm from each other. This would allow future studies on subcellular changes, related to the acrosome reaction, at the submicron resolution level under more physiological conditions, since AFM does not require fixing or staining of the samples.

Acrosome↗