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G M Waites

Publications and source records attributed to G M Waites.

At least 19 recordsLinked to original sources
PubMed1995

A non-human primate study (baboon; Papio hamadryas) to determine if a long-acting progestogen, levonorgestrel butanoate, combined with a long-acting androgen, testosterone buciclate, can suppress spermatogenesis: I. Dose-finding study.

This study in adult male baboons was conducted to establish the dose of a long-acting progestogen, levonorgestrel butanoate, and that of a long-acting androgen, testosterone buciclate, which, when combined, would achieve optimal and prolonged suppression of spermatogenesis. Two intramuscular injections of levonorgestrel butanoate at 3-month intervals and in the dose range 1-8 mg/kg reduced sperm production and plasma concentrations of testosterone, LH and FSH for periods of up to 6 months. The suppression of sperm production was greatest and most prolonged in the 4 mg/kg group. Two intramuscular injections of testosterone buciclate at 3-month intervals, and at doses of 4 and 8 mg/kg, induced variable changes in circulating levels of testosterone, elevated by the higher dose, and caused sperm suppression, in some animals to azoospermia. It was concluded that 8 mg/kg testosterone buciclate would provide adequate androgen replacement when combined with 4 mg/kg levonorgestrel butanoate as a putative male contraceptive regimen.

Adrenal Cortex Hormones↗
PubMed1995

A non-human primate study (baboon; Papio hamadryas) to determine if a long-acting progestogen, levonorgestrel butanoate, combined with a long-acting androgen, testosterone buciclate, can suppress spermatogenesis: II. Efficacy study.

Two combined injections of levonorgestrel butanoate (4 mg/kg) and testosterone buciclate (8 mg/kg) at 3-month intervals to adult male baboons initiated a decrease in sperm concentration from baseline values of 490x10(6)/ml to minimum values of 17x10(6/ml. This suppression was sustained until week 32, during which time between one and three azoospermic samples were collected from each of four out of five treated baboons in the period 10-24 weeks. Circulating plasma levels of LH and testosterone decreased to approximately 20-75% of baseline values. Plasma levels of cortisol declined to significantly reduced levels at weeks 22 and 36-44. All values returned to the baseline range by week 48. The combined administration of progestogen and androgen induced a more marked and sustained suppression to severe oligozoospermia or azoospermia than did the equivalent dose of progestogen alone (Goncharov et al., 1995). Although the dose of testosterone buciclate used did not maintain peripheral levels of testosterone in the normal range, it did not restimulate spermatogenesis. It was concluded that a combination drug regimen based on the novel long-acting levonorgestrel and testosterone esters could provide a contraceptive option for men.

Animals↗
PubMed1995

Factors in nonuniform induction of azoospermia by testosterone enanthate in normal men. World Health Organization Task Force on Methods for the Regulation of Male Fertility.

OBJECTIVE: To identify factors differentiating men becoming azoospermic from those remaining oligozoospermic within 6 months of T treatment. DESIGN: Prospective, open, noncomparative contraceptive efficacy study. SETTING: International multicenter study of 271 men in 10 centers in seven countries. PATIENTS: Data from 157 achieving azoospermia and 68 remaining oligozoospermic after 6 months of treatment were analyzed. The remaining 46 men were excluded as having unclassifiable suppression status due to discontinuation before completion of suppression. INTERVENTIONS: Weekly IM injections of 200 mg T enanthate. MAIN OUTCOME MEASURES: Anthropometric, seminal, hormonal, and biochemical data obtained before, during, and after treatment as potential predictors of consistent azoospermia. RESULTS: Azoospermic men had [1] faster rates of fall in sperm output and, after a delay of 75 +/- 4 days (mean +/- SE) for sperm to reappear in the ejaculate, exhibited a faster rate of recovery of sperm output; [2] higher pretreatment levels of FSH (mean +/- SE; 3.7 +/- 0.3 versus 2.7 +/- 0.4 mIU/mL [conversion factor to SI units, 1.00]); and [3] (if treated for > 15 months) a prolonged after treatment rebound in gonadotropins compared with nonazoospermic men. There were no other differences in pretreatment variables or plasma T levels and changes in androgen-sensitive markers during treatment. None of the variables explained the higher rates of azoospermia among men in Chinese (91%, n = 3) compared with non-Chinese centers (60%, n = 7). CONCLUSION: Nonuniformity of T-induced azoospermia among healthy fertile men is not due to anthropometric or ethnic differences, to variations in androgen effects, or to poor compliance with treatment. The heterogeneity in individual susceptibility to T-induced azoospermia is most consistent with quantitative differences in the hormonal regulation of spermatogenesis and is likely to be evident with other hormonal methods for male contraception.

Adult↗
PubMed1991

Thermoregulation of the scrotum and testis: studies in animals and significance for man.

This article reviews the extensive information available from experiments on animals concerning the thermal monitoring provided by the scrotum. Cutaneous temperature receptors initiate responses which follow unique pathways and undergo "switching" processing within the central nervous system. These pathways evoke reflex responses which are subject to control from receptors in other regions of the body, including the skin and temperature sensitive neurones in the brain and spinal cord. The local thermoregulatory responses of the scrotum, e.g., sweating and vasomotor changes, clearly have a role to play in the protection of the testis against temperature elevation in both man and animals. It is as yet more difficult to propose how general reflex responses may be of benefit in the protection of spermatogenesis against heat damage. This meeting should provide the stimulus for further work. The need is urgent since it may also provide a means to apply this knowledge to a better understanding of male infertility and possibly to speed the development of male methods of fertility regulation.

Animals↗
PubMed1986

Effects of passive immunization against oestradiol-17 beta on some endocrine values of the male lamb.

Passive immunization of male lambs against oestradiol-17 beta from 2 to 16 weeks of age significantly elevated androgen concentrations in plasma and depressed the median eminence content of dopamine. Removal of endogenous oestrogens had no significant effects on plasma FSH, LH or prolactin concentrations or on testicular growth and hypothalamic content of GnRH. These results suggest that endogenous oestrogens may indirectly suppress testicular androgen secretion by exerting a stimulatory influence on hypothalamic dopaminergic neurones, which in turn may inhibit GnRH secretion by the median eminence.

Androgens↗
PubMed1986

Male fertility regulation: recent advances.

Acceptable antifertility drugs for men are proving difficult to produce. Such drugs must aim to achieve complete azoospermia over a long period. This requirement may be relaxed only if it can be shown that the residual sperm produced by men whose spermatogenesis has been suppressed by antifertility drugs to oligospermia are incapable of fertilizing ova. Hormonal methods involving suppression of the secretion of gonadotrophin hormones by the pituitary gland invariably require androgen supplementation, and the use of steroids either alone or in combination requires careful monitoring for their side-effects. A chemical (non-hormonal) approach involving the incapacitation of sperm in the epididymis has been shown to be feasible in animal studies using alpha-chlorohydrin and 6-chloro-6-deoxy sugars, although such compounds cannot be developed for human use because of their toxicity. Immunological approaches have the inherent problem of delivery of the antibody to the target. While the search for new and safer chemical and hormonal approaches goes on, the recent evidence that vasectomy offers a safe surgical option leaves responsible men with some choice to add to the condom.

Androgens↗
PubMed1983

Rapid compensatory hypertrophy of the lamb testis after neonatal hemiorchidectomy: endocrine and light microscopical morphometric analyses.

The testis mass of lambs hemiorchidectomized (HO) within 1 week of birth exceeded that of control testes by 23%, 67%, and 114% at 4, 8, and 12 weeks; the epididymis was 39% heavier than control epididymides by 12 weeks. The seminiferous tubular mass in HO testes grew at a faster rate than in control testes to achieve full compensation by about 10 weeks; Sertoli cell division was augmented in the 1- to 4 week phase and Sertoli cell cytoplasm increased throughout. The major growth response of the interstitium of HO testes occurred in the 1- to 4 week period but did not obtain full compensation by 12 weeks; the vascular component responded to HO by rapid growth in the 8- to 12 week period. There was a low incidence of division amongst gonocytes (prespermatogonia) in both groups of lambs but at 12 weeks spermatogonial mitoses, spermatocytes, and tubular lumina were present in four out of four HO tests but only one of three control testes. In the same lambs, HO induced an immediate increase in circulating plasma concentrations of FSH to 3-4 x control values at 8 weeks, which were then suppressed to near control values by 10 weeks. Apart from transient increases in LH (at 4-5 weeks) and testosterone (6-7 weeks) above control values, there were no differences between HO and control lambs in the circulating concentrations of any other hormone measured (LH, GH, TSH, PRL, and testosterone). The evidence suggests that the major prepubertal influence on testicular development and growth in lambs is the FSH-provoked response of the Sertoli cells.

Animals↗
PubMed1983

Effects of hemicastration at various ages and of oestradiol-17 beta on plasma concentrations of gonadotrophins and androgens, testicular growth and interstitial cell responses in prepubertal lambs.

The effect of the removal of one testis from cross-bred lambs at 1, 4, 8 or 12 weeks of age on plasma FSH, LH and testosterone was studied until 16 weeks of age. Hemicastration at all ages elicited a significant increase in plasma FSH compared to controls without a corresponding change in plasma LH or testosterone. The raised FSH after hemicastration at 1 or 4 weeks of age was suppressed to control levels between weeks 7 and 8; such a suppression was not observed in the 4 weeks following hemicastration at 8 or 12 weeks of age. The weight of the remaining testis had increased compared with the control by 12 weeks of age after hemicastration at 1 week (+ 69%), 4 weeks (+ 13%) and 8 weeks (+ 40%); hemicastration at 12 weeks of age also resulted in growth of the remaining testis at 16 weeks (+ 82%). The total androgen production of interstitial cells in response to ovine LH stimulation in vitro did not differ significantly between lambs of 1 and 12 weeks of age, or in animals of 4, 8 and 12 weeks of age after hemicastration at 1 week of age. Subdermal implantation of oestradiol-17 beta into 1-week hemicastrated lambs at the time of operation or at 6 weeks of age increased plasma oestradiol concentrations by approximately 2-4-fold, prevented the FSH and testicular growth responses to hemicastration and suppressed plasma LH and testosterone to levels lower than those in control lambs. The total androgen response of interstitial cells from the remaining testis of oestradiol-implanted lambs at 12 weeks of age was significantly reduced. We suggest that the pituitary-testis axis varies in sensitivity during the prepubertal period although the interstitial cellular response of the testis to LH stimulation remains constant.

Animals↗
PubMed1982

Immunocytochemical evidence for the specific localization of aldose reductase in rat Sertoli cells.

Evidence that the enzyme aldose reductase (AR) is specifically located in Sertoli cells is presented by means of an established immunocytochemical technique and with a variety of approaches. By staining tissue sections, the enzyme was shown to be present in Sertoli cells at birth and the intensity of the immunocytochemical stain increased by 5 days of age to that found in the testes of older rats. By means of enzyme dispersion of mature testes; the culture of enriched Sertoli cell preparations from the testes of immature rats; and the collection of newly released testicular spermatozoa in rete testis fluid, it was shown that immunoreactive AR was not present in any testicular cell type except the Sertoli cell. The significance of the specific localization in Sertoli cells of a principal enzyme concerned in the sorbitol or polyol pathway for the conversion of aldose sugars to their corresponding ketoses is discussed.

Aging↗
PubMed1982

Activities of various 6-chloro-6-deoxysugars and (S) alpha-chlorohydrin in producing spermatocoeles in rats and paralysis in mice and in inhibiting glucose metabolism in bull spermatozoa in vitro.

6-Chloro-6-deoxyglucose, 6-chloro-6-deoxymannose, 6-chloro-6-deoxy-fructose, 6-chloro-6-deoxyglucitol, 6-chloro-6-deoxygalactose and (S) alpha-chlorohydrin all produced spermatocoeles in the ductuli efferentes and epididymis of the rat and were neurotoxic in the mouse, but only alpha-chlorohydrin caused substantial inhibition of glucose metabolism in bull spermatozoa in vitro. The relative potencies of the compounds in producing spermatocoeles reflected their activities as reversible antifertility agents in the rat but compared to the others 6-chloro-6-deoxymannose was considerably less neurotoxic to mice than might have been anticipated from its contraceptive dose. Thus different metabolites may be responsible for causing the antifertility and the neurotoxic effects.

Animals↗
PubMed1981

The effect of high doses of 6-chloro-6-deoxyglucose on the rat.

Male rats given 6-chloro-6-deoxyglucose (240 mg/kg/day for 28 days) developed spermatocoeles in their ductuli efferentes or caput epididymides. They had a lower serum triglyceride content than controls (0.87 +/- 0.19 vs 1.84 +/- 0.19 mM, Mean +/- SEM; n = 6) and gained less weight (2.55 +/- 0.37 vs 4.1 +/- 0.96 g/day, Mean +/- SEM; n = 6). There was no effect on female rats which received the same treatment. Spermatocoeles could also be produced by a single dose of 6-chloro-6-deoxyglucose, the threshold dose was between 180 and 240 mg/kg. Glucose oxidation by liver, brain, kidney and diaphragm from rats given 6-chloro-6-deoxyglucose (240 mg/kg/day for 14 days) was the same as in controls but was decreased in seminiferous tubules (0.32 +/- 0.06 vs 0.74 +/- 0.02 mumol [U-14C]glucose oxidised to 14CO2/g fresh wt/h, Mean +/- SEM; n = 3). The activity of glyceraldehyde-3-phosphate dehydrogenase [E.C. 1.2.1.12] in liver, brain, testis or muscle from rats given 6-chloro-6-deoxyglucose (24 mg/kg/day for 14 days) showed little change although its activity in spermatozoa was dramatically decreased.

Animals↗
PubMed1981

Effects of 6-chloro-6-deoxysugars on glucose oxidation in rat spermatozoa.

6-Chloro-6-deoxyfructose or 6-chloro-6-deoxyglucitol (greater than 90 mumol/kg/day), 6-chloro-6-deoxyglucose or 6-chloro-6-deoxymannose (greater than 120 mumol/kg/day) and 6-chloro-6-deoxygalactose (greater than 300 mumol/kg/day) all had an antifertility action in the male rat when given by mouth. Spermatozoa from the infertile rats were unable to oxidize glucose. This effect was always produced by a lower dose than the antifertility effect and the threshold dose for the 2 effects varied in a parallel fashion between the different 6-chloro-6-deoxysugars. Glucose oxidation appeared to be inhibited at the triose phosphate isomerase or glyceraldehyde 3-phosphate dehydrogenase reaction. These effects of 6-chloro-6-deoxysugars are similar to those of alpha-chlorohydrin. The activities of the glycolytic enzymes were greatly in excess of the observed flux through the pathway and high concentrations of glucose 6-phosphate and triose phosphate accumulated in rat spermatozoa incubated with 2 mM-D-glucose.

Animals↗
PubMed1980

The control of male fertility by 6-chloro-6-deoxysugars.

1. 6-Chloro-6-deoxyglucose (24 mg/kg/day) produces a rapid and reversible antifertility effect in the male rat but high doses (greater than 200 mg/kg/day) produce spermatocoeles. In the mouse repeated high doses (480 mg/kg/day) cause paralysis of the hind limbs but there is no effect on fertility. 2. Spermatozoa from rats treated with 6-chloro-6-deoxyglucose (24 mg/kg/day) are unable to metabolize glucose and rapidly become exhausted when glucose is the only substrate supplied. Glycolysis is inhibited at the glyceraldehyde 3-phosphate dehydrogenase reaction. These spermatozoa can obtain energy by oxidizing pyruvate or lactate. 3. The side effects prevent the use of 6-chloro-6-deoxyglucose by humans but a fuller understanding of their mode of action may lead to the development of compounds with a more selective attack on spermatozoa.

Animals↗
PubMed1980

Functional relationships of the mammalian testis and epididymis.

The development of knowledge in four areas of research in male reproductive physiology of particular interest is reviewed. The concept of the blood-testis barrier (BTB), which arose following dye exclusion from the seminiferous tubules, has now been established as the differential transfer from interstitial fluid to tubular and rete testis fluids of molecules of physiological importance. The composition of fluid collected mostly from the rete testis of several species, not only reflects the nature of the barrier, but also the secretory capacity of the Sertoli cell. The functional significance of the transfer of molecules into testicular fluid and the composition of the fluid flowing into the epididymis are discussed. Sertoli cells establish the structural basis of the BTB during puberty and divide the seminiferous epitheliuym into basal and adluminal compartments. The Sertoli cell is the prime target for follicle stimulating hormone (FSH). The responses evoked by FSH are discussed, including special mention of androgen binding protein (ABP) and the protein hormone, 'inhibin', with FSH-suppressing properties. The control of FSH in the lamb is mentioned including new evidence to support a tubular source of a feedback agent with significance during the impuberal stage. Finally, some of the biochemical properties of the epididymis and its fluid contents are reviewed and the epididymal sperm are identified as the site of the antifertility action of the 6-chloro-6-deoxy sugars.

Animals↗