Disruption of the Metabolism, Motility and Morphology of Spermatozoa by Injection of a-Chlorohydrin Into Rams

Pd, Brown-Woodman; White, I. G.

doi:10.1071/bi9760545

Cited by 9 publications

(11 citation statements)

References 26 publications

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“…a-Chlorohydrin significant reduction in all the metabolic parameters of the ram spermatozoa, ie, oxygen consumption, C 0 2 production, fructose utilization, lactic acid accumulation, and dpm C14 0 2 . The total absence of lactate accumulation clearly demonstrated the extent of the inhibition of glycolysis, and a similar effect was seen with spermatoza collected from rams after administration of a-chlorohydrin [Brown-Woodman and White, 1976;Brown-Woodman et al, 19781.…”

Section: Results a N D Discussionsupporting

confidence: 54%

“…This value was substantially reduced as the concentration of a-chlorohydrin increased. When a-chlorohydrin is injected into rats at a daily dose of 5 mg/kg, fertility is lost completely [Brown-Woodman et al, 1976;19791. Assuming even distribution of a-chlorohydrin over 80% of the body, spermatozoa in the epididymis would be exposed to an a-chlorohydrin concentration of 0.04 mM. However, the levels could be higher, since a-chlorohydrin has been shown to be concentrated in the cauda epididymis [Crabo and Appelgren, 19701. Compound I reduced at a concentration of compound I below 10 mM (Table 2).…”

Section: Results a N D Discussionmentioning

confidence: 99%

“…However, the fact that compound I was less effective than a-chlorohydrin in depres-Apart from a-chlorohydrin, compound I1 was one of the most potent inhibitors of ram sperm metabolism; oxidative metabolism was inhibited by 1 .O mM and glycolysis by 0.1 mM (Table 3). This compound also produced infertility in male rats at a concentration equivalent, on a molar basis, to 5 mg of a-chlorohydrin/kg, injected daily for 14 days and it was not toxic at this dose [Brown-Woodman et al, 1976;19791. Compound I1 appears to have potential as a male antifertility agent, but further work is required to determine whether it has any of the toxic side effects of a-chlorohydrin at higher doses.…”

Section: Compound IImentioning

confidence: 90%

“…This compound inhibited the oxidative metabolism of ram spermatozoa at 10 mM and glycolysis at 1 mM (Table 4). Obviously, the compound is not as active as a-chlorohydrin in suppressing the metabolism of ram spermatozoa in vitro or reducing the fertility of male rats [Brown-Woodman et al, 1976;19791. Compound I V metabolism of ram spermatozoa and 1 .O mM was required for a significant effect ( Table 5). Fructose utilization was reduced at 0.1 mM, but some lactic acid still accumulated at this concentration, presumably because its oxidation was not suppressed as much as with achlorohydrin.…”

Section: Compound Illmentioning

confidence: 99%

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Inhibition of the metabolism of ram spermatozoa by derivatives of α‐chlorohydrin

1981

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The effects of the male antifertility agent, α‐chlorohydrin, six of its derivatives, and glycidol were studied on the metabolism of washed ram spermatozoa in vitro with fructose as substrate. The α‐chlorohydrin derivatives were the amino, the phosphorylated, and four glycol‐bridge (ketal) compounds. All compounds except glycidol, in a concentration between 0.1 and 100 mM, reduced the aerobic glycolsis and/or oxidation of fructose. However, there was not a high correlation between the ability of these compounds to inhibit the metabolism of ram spermatozoa in vitro and their antifertility activity when administered to male rats. Other factors are clearly involved in their antifertility activity, eg, the concentration of the compounds in the epididymis and their conversion of either more or less spermicidal compounds in the body.

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Section: Results a N D Discussionsupporting

confidence: 54%

Section: Results a N D Discussionmentioning

confidence: 99%

Section: Compound IImentioning

confidence: 90%

Section: Compound Illmentioning

confidence: 99%

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Inhibition of the metabolism of ram spermatozoa by derivatives of α‐chlorohydrin

1981

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“…These analogs are metabolized to (S)-3-chlorolactaldehyde, a competitive substrate inhibitor of GAPD activity in mammalian sperm (Stevenson and Jones, 1985). They caused dose-dependent inhibition of sperm glycolysis and motility at concentrations that did not inhibit GAPD activity in other tissues (Brown-Woodman et al, 1978;Brown-Woodman and White, 1976;Ford and Harrison, 1983). These studies provide additional evidence that glycolysis is necessary for sperm motility and fertilization, and further suggest that GAPDS serves a pivotal role in this process.…”

Section: Glycolysismentioning

confidence: 83%

Fibrous sheath of mammalian spermatozoa

Eddy

Toshimori

O’Brien

2003

Microscopy Res & Technique

337

253

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The fibrous sheath is a unique cytoskeletal structure surrounding the axoneme and outer dense fibers and defines the extent of the principal piece region of the sperm flagellum. It consists of two longitudinal columns connected by closely arrayed semicircular ribs that assemble from distal to proximal throughout spermiogenesis. The fibrous sheath is believed to influence the degree of flexibility, plane of flagellar motion, and the shape of the flagellar beat. Nearly half of the protein in fibrous sheaths isolated from mouse sperm is AKAP4. This protein and two others, AKAP3 and TAKAP-80, have anchoring sites for cAMP-dependent protein kinase. AKAP3 also anchors ropporin, a spermatogenic cell-specific protein that is linked through rhophilin to the small GTPase Rho. Other proteins associated with the fibrous sheath include two enzymes in the glycolytic pathway. Glyceraldehyde 3-phosphate dehydrogenase-s (GAPDS) is the product of a gene expressed only in spermatogenic cells, while hexokinase type 1-s (HK1-S) is derived from alternative transcripts present only in spermatogenic cells. Most of the other glycolytic enzymes in sperm have unique structural or functional properties. The fibrous sheath also contains a spermatogenic cell-specific member of the mu-class glutathione S-transferase family (GSTM5) and an intermediate filament-like protein (FS39). These and other observations indicate that the fibrous sheath functions as a scaffold for proteins in signaling pathways that might be involved in regulating sperm maturation, motility, capacitation, hyperactivation, and/or acrosome reaction and for enzymes in the glycolytic pathway that provide energy for the hyperactivated motility of sperm that allows them to penetrate the zona pellucida.

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Synchronous Assessment of Sperm Motility and Fertilizing Ability in the Hamster Following Treatment With α‐Chlorohydrin

SLOTT,

JEFFAY,

SUAREZ

et al. 1995

Journal of Andrology

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To Investigate the relationship between sperm motion parameters and fertilizing ability, a model was developed to assess both of these endpoints synchronously using a toxicant that inhibits sperm motion. α‐Chlorohydrin (ACH) was administered daily for 4 days to male hamsters at 0,33,49,66, and 83 mg/kg body weight. These males were then allowed a 45‐minute breeding period with untreated estrus females on the morning of day 5. One hour after breeding, sperm samples were surgically recovered from the uteri of the females for motility analysis. Six hours later, eggs were flushed from the oviducts and evaluated for fertilization. Cauda epididymal sperm were also collected from the males shortly after breeding. Proportions of motile and progressively motile sperm were manually quantified, and overall sperm velocity and the velocity of representative vigorously swimming sperm in both the uterine and epididymal samples were measured by computer‐aided sperm analysis. Significant decreases in in vivo fertilization rates and epididymal sperm motion parameters were observed at 66 and 83 mg/kg ACH, whereas uterine sperm motion was adversely affected at all ACH dosages used. All sperm motion parameters except the percentage of motile sperm in the epididymis were significantly correlated with fertilization rates by both linear and logistic regression. Overall, uterine and epididymal sperm endpoints predicted fertilizing ability comparably well. Stepwise multiple linear regression gave a model containing epididymal sperm velocity (EVCL) and uterine sperm percent motility (UMOT) with an R2 value of 0.649. Stepwise multiple logistic regression gave models containing EVCL alone and EVCL and UMOT in binary (fertile/infertile) and quantal models, respectively.

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Disruption of the Metabolism, Motility and Morphology of Spermatozoa by Injection of a-Chlorohydrin Into Rams

Abstract: Aust. J. Bioi. Sci., 1976, 29, 545-55 Ejaculated spermatozoa from rams given intramuscular injections of Show more

Cited by 9 publications

References 26 publications

Inhibition of the metabolism of ram spermatozoa by derivatives of α‐chlorohydrin

Inhibition of the metabolism of ram spermatozoa by derivatives of α‐chlorohydrin

Fibrous sheath of mammalian spermatozoa

Synchronous Assessment of Sperm Motility and Fertilizing Ability in the Hamster Following Treatment With α‐Chlorohydrin

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