The production of lactate and pyruvate as sensitive indices of altered rat Sertoli cell function in vitro following the addition of various testicular toxicants

Williams, Joseph F.; Foster, Paul M.D.

doi:10.1016/0041-008x(88)90346-8

Cited by 49 publications

(9 citation statements)

References 27 publications

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“…The fairly marked stage-dependent differences in COX II mRNA in pachytene spermatocytes may also have some significance with regard to the mechanism of action of MAA. This toxicant is thought to act on the spermatocytes themselves, rather than on the Sertoli cells, and there is a suggestion that MAA may exert its effect by interfering in some way with energy metabolism [48]. In this respect, MAA treatment has been shown to cause mitochondrial swelling in pachytene spermatocytes prior to their degeneration [49] and to cause a change in the mitochondrial mass distribution of the round spermatids that survive MAA treatment [50].…”

Section: Discussionmentioning

confidence: 98%

Mitochondrial Cytochrome C Oxidase II Messenger Ribonucleic Acid is Expressed in Pachytene Spermatocytes at High Levels and in a Stage-Dependent Manner during Spermatogenesis in the Rat

Saunders

Millar

West

et al. 1993

Biology of Reproduction

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Screening of a rat seminiferous tubule library (stages VI-VIII) resulted in isolation of several clones to the same abundant mRNA. Sequencing revealed that these encoded all or part of the second subunit of cytochrome C oxidase (COX II), the terminal enzyme in the electron transport chain located in mitochondria. The pattern of expression of the COX II mRNA in the testis was examined by Northern blot and in situ hybridisation combined with specific depletion of pachytene spermatocytes or Leydig cells by treatment with methoxyacetic acid (MAA) or ethane dimethane sulphonate (EDS), respectively. COX II mRNA was found to be strongly expressed in pachytene spermatocytes in adult and prepubertal rats, with the highest levels of expression at stages VII-VIII of the spermatogenic cycle. Although this is the androgen-dependent stage, Northern analysis of total testicular RNA showed that expression of COX II mRNA was not altered detectably by EDS-induced androgen withdrawal nor was expression altered detectably by 24-h treatment with high doses of FSH. Treatment of rats with MAA, which selectively depletes seminiferous tubules at most stages of pachytene spermatocytes, resulted in a marked reduction in COX II mRNA. In the absence of pachytene spermatocytes, COX II mRNA was visualized in preleptotene spermatocytes and in Sertoli cell cytoplasm. The expression of COX II in Sertoli cells was confirmed by examination in situ of a testis devoid of most germ cells and by Northern analysis of RNA from an adult Sertoli cell-enriched preparation. However, using either approach the amount of mRNA in Sertoli cells was considerably lower than that in pachytene spermatocytes. Cytochrome C oxidase has thirteen subunits, three of which (I-III) are encoded on the mitochondrial genome. The physiological significance of the high levels of expression of COX II mRNA in pachytene spermatocytes and its stage-dependent changes is unknown but they presumably reflect requirements for alterations in energy demand as these cells enter the final stages of meiosis. The stage-dependent differences in expression of COX II mRNA in pachytene spermatocytes may also explain differences in the susceptibility of these cells to depletion by MAA.

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Section: Discussionmentioning

confidence: 98%

Mitochondrial Cytochrome C Oxidase II Messenger Ribonucleic Acid is Expressed in Pachytene Spermatocytes at High Levels and in a Stage-Dependent Manner during Spermatogenesis in the Rat

Saunders

Millar

West

et al. 1993

Biology of Reproduction

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“…The Sertoli cell is considered the primary target of phthalate monoester toxicity. Phthalate monoesters affect the normal nurse function of the Sertoli cell and its ability to produce lactate and pyruvate from glucose, an essential function of the Sertoli cell in the sustenance of germ cells, which cannot use glucose as an energy substrate (Williams and Foster 1988). Studies have also shown that select phthalate monoesters may interfere with the ability of Sertoli cells to respond to their normal endogenous ligand, follicle-stimulating hormone (FSH).…”

Section: Discussionmentioning

confidence: 99%

Evidence of Interaction between Polychlorinated Biphenyls and Phthalates in Relation to Human Sperm Motility

Hauser

Williams

Altshul³

et al. 2005

Environ Health Perspect

152

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Previously, we reported evidence of inverse associations between exposure to some polychlorinated biphenyls (PCBs) and some phthalate monoesters in relation to semen parameters, specifically sperm motility. Because humans are exposed to both phthalates and PCBs and because experimental studies suggest that PCBs may interact with glucuronidative enzymes that are responsible for phthalate metabolism, we explored the potential interaction between phthalates and PCBs in relation to human semen quality. We studied 303 men who were partners in subfertile couples seeking infertility diagnosis from the andrology laboratory at Massachusetts General Hospital. Semen parameters were dichotomized based on World Health Organization reference values, and phthalate and PCB levels were dichotomized at their respective medians. After adjusting for age and abstinence time, for below reference sperm motility there was a greater than additive interaction between monobenzyl phthalate and PCB-153 [relative excess risk due to interaction (RERI) = 1.40; 95% confidence interval (CI), 0.41–3.22], sum of PCBs (RERI = 1.24; 95% CI, 0.15–2.94), and cytochrome P450 (CYP450)-inducing PCBs (RERI = 1.30; 95% CI, 0.21–3.06). For below-reference sperm motility, there was also a greater than additive interaction between monobutyl phthalate (MBP) and PCB-153 (RERI = 1.42; 95% CI, 0.09–3.76) and CYP450-inducing PCBs (RERI = 1.87; 95% CI, 0.56–4.52) and a suggestive interaction between MBP and sum of PCBs (RERI = 1.35; 95% CI, −0.11 to 3.48). In conclusion, because there are important risk assessment and public health implications of interactions between these two ubiquitous classes of compounds, further studies need to be conducted to confirm these results and identify potential mechanisms of interactions.

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“…Therefore increased lactate production seems to be a sensitive and specific response to toxin exposure, at least for the proven Sertoli cell toxicants 1,3‐dinitrobenzene (1,3‐DNB) and mono‐(2‐ethylhexyl)phthalate (MEHP). Their derivatives 1,2‐DNB, 1,4‐DNB, di‐(2‐ethylhexyl)phthalate, and the metabolite 2‐ethylhexanol, which did not affect male reproduction in vivo , also failed to cause any significant alteration of lactate levels when exposed to Sertoli cells in vitro ( Williams & Foster, 1988). Toxicants that primarily target spermatocytes, e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Toxicants that primarily target spermatocytes, e.g. ethylene glycol monomethyl ether ( Foster et al ., 1984 ) and its major metabolite, methoxyacetic acid (MAA), also had no effect on lactate production by cultured Sertoli cells ( Williams & Foster, 1988).…”

Section: Discussionmentioning

confidence: 99%

Sertoli cells as a target for reproductive hazards

et al. 2000

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Male fertility can be impaired by various toxicants. Some of them are known to target mainly Sertoli cells, which play an essential role in spermatogenesis. In this study, the in vitro response of immature rat Sertoli cells to various environmental pollutants, including pesticides, oestrogenic compounds and heavy metals, has been investigated. Mitochondrial dehydrogenase activity has been used to measure Sertoli cell viability, while production of lactate and secretion of inhibin B have been used as general and specific cell markers. Sertoli cell viability was not affected after 24-h exposure to lindane, DDT, ethinyloestradiol or bisphenol A in the concentration range analysed (up to 100, 25 or 50 microM, respectively). In contrast, mercury(II) (EC50 = 31 microM) and cisplatin (15% decrease in viability at 100 microM) induced some cytotoxic effect. With the exception of the pesticide DDT, all chemicals investigated induced a significant dose-dependent increase in lactate production after 24-h exposure to Sertoli cells. Owing to the cytotoxic effect of mercury(II), lactate levels dropped again at concentrations above 20 microM. The pesticide lindane (but not DDT) and both oestrogens significantly increased the production of the Sertoli cell specific hormone inhibin B without affecting cell viability. In contrast, the heavy metals mercury(II) and platinum(II) markedly decreased inhibin B levels. This sharp decrease was already significant at metal concentrations that reduced Sertoli cell viability only moderately (10-15%). In conclusion, the secretion of lactate and inhibin B by immature rat Sertoli cells seems to be a useful and sensitive marker with which to explore potential Sertoli cell toxicants.

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The production of lactate and pyruvate as sensitive indices of altered rat Sertoli cell function in vitro following the addition of various testicular toxicants

Cited by 49 publications

References 27 publications

Mitochondrial Cytochrome C Oxidase II Messenger Ribonucleic Acid is Expressed in Pachytene Spermatocytes at High Levels and in a Stage-Dependent Manner during Spermatogenesis in the Rat

Mitochondrial Cytochrome C Oxidase II Messenger Ribonucleic Acid is Expressed in Pachytene Spermatocytes at High Levels and in a Stage-Dependent Manner during Spermatogenesis in the Rat

Evidence of Interaction between Polychlorinated Biphenyls and Phthalates in Relation to Human Sperm Motility

Sertoli cells as a target for reproductive hazards

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