Karen Chou

Effect of human dietary exposure levels of genistein during gestation and lactation on long-term reproductive development and sperm quality in mice.

The objective of the present study was to determine the long-term reproductive effects of gestational and lactational exposure (0, 0.1, 0.5, 2.5 and 10 mg/kg/day) to genistein on male mice at levels comparable to or greater than human dietary exposures. Testicular growth, sperm count and motility, and sperm fertilizing ability in vitro was assessed in male offspring on postnatal days (PND) 105 and 315. Selected genes were also examined by real-time PCR to determine whether genistein caused changes in gene expression similar to those previously observed with diethylstilbestrol (DES). No significant treatment-related effects on male offspring body weight, anogenital distance, seminal vesicle weight or testis weight were observed. There were also no significant effects on sperm count, the percent of motile sperm or the number of motile sperm at any age. The in vitro fertilizing ability of epididymal sperm was increased significantly in the high-dose group approximately 17% (P < 0.001) on PND 105 and 315. The results indicate that developmental exposure of mice to genistein at human exposure levels does not induce adverse effects on sperm quality or changes in testicular gene expression similar to DES.

Effects of gestational and lactational exposure to Aroclor 1242 on sperm quality and in vitro fertility in early adult and middle-aged mice.

The objective of this study was to examine the effects of gestational and lactational exposure to Aroclor 1242 (0, 10, 25, 50, and 100 mg/kg-bw) on male fertility. Doses were administered to C57BL6 female mice orally every two days from two weeks before mating, during mating, and through gestation until postnatal day 21. Male B6D2F1 offspring were examined for anogenital distance, organ development, epididymal sperm count, sperm motility, and in vitro fertility at 16 and 45 weeks of age. Stomach samples of pups nursing from PCB-treated mothers in the 50 mg/kg dose group were analyzed for PCBs and chlorobiphenylols by high resolution gas chromatography coupled with low resolution mass spectrometry. It was estimated that the nursing pups were exposed to 0.2, 0.6, 1.2, and 2.4 mg/kg/day total PCBs in the 10, 25, 50, and 100 mg/kg dose groups, respectively. This exposure level approaches the maximum FDA recommended levels for PCBs in food and breast milk. The composition of the PCBs in the stomach samples was different from the parent mixture, as there was a higher proportion of heavily chlorinated congeners, as well as chlorobiphenylols. Anogenital distance at weaning, and liver, thymus, and testes weight at 16 and 45 weeks of age were not affected by PCB exposure. Epididymal sperm velocity and linearity were significantly increased in the 25 mg/kg dose group at 16 weeks of age. Sperm count was increased by 36% in this dose group (P = 0.06). By 45 weeks of age, average sperm count in this dose group was similar to that of controls. With the exception of the 50 mg/kg dose group at 16 weeks of age, sperm fertilizing ability in vitro was significantly decreased in all PCB-exposed groups at 16 and 45 weeks of age. These results suggest that fertility in the adult mouse is susceptible to developmental exposure to Aroclor 1242 and is independent of testis weight or epididymal sperm count.

Phthalates in Food and Medical Devices

SummaryPhthalates are ubiquitous environmental chemicals with a broad range of potential adverse health effects. Exposure pathways include air, water, packaged food and household products. Biological effects include disruption of the balance of sex hormones, allergic reactions, and enzyme inhibition. Carcinogenicity is seen in animals. In human studies, phthalates have been associated with poorer sperm quality, the symptomatology of asthma, and shortened AGD. Given the widespread use of phthalates in industrialized countries, further research, particularly on birth outcomes, endocrine disruption and child development are greatly needed.

Changes in intracellular calcium of porcine sperm during in vitro incubation with seminal plasma and a capacitating medium.

The intracellular free Ca2+ concentration in ejaculated, porcine sperm was determined with a fluorescent, Ca2(+)-specific probe, Fura 2. Following suspension of sperm in a medium capable of sustaining capacitation and the acrosome reaction, the intracellular [Ca2+] increased from an initial value of about 75 nM to a peak value of 130 nM, after about 4 to 5 h of incubation. Within this period of time, a peak value of 246 nM was attained when sperm was incubated in seminal plasma. Ca2+ uptake is presumably not associated with membrane potential-dependent channels. The results indicate that a pronounced increase in intracellular free Ca2+ occurs towards the end of the incubation period when rather synchronous acrosome reactions take place in the sperm population, either in capacitating medium or in seminal plasma.

Aluminium impacts elements of the phosphoinositide signalling pathway in neuroblastoma cells

Inositol phosphate formation was examined in aluminium-treated murine neuroblastoma cells labelled with [3H]-myoinositol. Employing fluoride-stimulated intact cells, aluminium (0.2μM to 1 mM) reduced inositol phosphate formation in a dose-dependent manner. In digitonin-permeabilized cells, stimulated with nonhydrolyzable GTP[S], inositol phosphate formation was also inhibited by increasing aluminium doses; the IC50 value was about 20μM aluminium, while the inositol phosphate level was reduced 2.5 to 3 fold by 50μM aluminium. The inhibitory effect of aluminium (50μM) could not be reversed by increasing GTP[S] concentrations up to 500μM. Prechelation of aluminium to citrate or EGTA completely abolished the aluminium-triggered inhibition of fluoride-stimulated inositol phosphate formation in intact cells, but had little effect on the inhibition of permeabilized cells stimulated with GTP[S]. In neuroblastoma cells phosphoinositide hydrolysis could be evoked either through a pathway involving the Mg2+/guanine nucleotide binding (Gp) protein, or via a pathway operative in the presence of high intracellular Ca2+ concentrations. In the Mg2+/Gp protein-mediated pathway, formation of inositol triphosphate, IP3, inositol diphosphate, IP2, and inositol monophosphate, IP, was apparently inhibited by aluminium in an interdependent manner. As to the Ca2+-mediated pathway, aluminium application mainly diminished the release of IP3. Following interiorization, aluminium thus acts upon elements critical for phosphoinositide-associated signal transduction. An aluminium target apparently resides on the Gp protein. Phosphatidylinositol-4,5-diphosphate-specific phospholipase C probably harbours a second aluminium target.

The membrane potential changes polarity during capacitation of murine epididymal sperm.

The membrane potential in murine epididymal sperm was determined with a voltage-sensitive, fluorescent probe. In freshly collected sperm, the potential was inside-negative, viz., -13 mV, and was associated with an intracellular K+ concentration of about 122 mM. Following incubation of sperm in a medium capable of sustaining capacitation and fertilization efficacy, the potential became gradually positive. An inside-positive potential, +24 mV, was obtained after 40 min of incubation, concomitant with an intracellular K+ concentration of approximately 30 mM. At this time, about 70 percent of sperm had capacitated. An inside-positive membrane potential may play a role in facilitating the acrosome reaction.

Paraoxon inhibits fertilization of mouse gametes in vitro

Potential exposure of mammals to organophosphate pesticides and their metabolites is recognized (Frank et al. 1991). Organophosphates have been implicated frequently in suboptimal reproductive performance in males and females of various species. Studies have shown that altered androgen metabolism (Krause, 1977), pathological changes in testes and adrenals (Chapin et al. 1988; Oishi et al. 1982; Dunnick et al. 1984), and chromosome aberrations (Kiraly et al. 1979) may be responsible for decreased reproductive performance in animals exposed to organophosphates. Also, organophosphates may have direct effects on sperm fertilizing ability without producing organic changes or altering spermatogenesis (Beck 1953; Harbison et al. 1976). This effect on sperm may occur in the epididymides, seminal plasma, or female reproductive tract.

Elevation of intracellular free calcium levels in sperm in response to long-term feeding of fungicides to mice

Abstract Cored samples of the Kubanni River sediments were analysed for their elemental composition using Neutron Activation Analysis(HAA). Long‐lived reactor irradiation of the samples at thermal and epithermal neutron fluxes of 2.15 × 1010 n cm‐2 s‐1 and 1.78 × 1011 n cm‐2 s‐1 respectively revealed the presence of 18 elements (Sc, Cr, Fe, As, Co, Rb, Y. Cs, Ba, Ce, Nd, Eu, Tb, Lu, Hf, Ta, U and Th) with varying concentrations for each core level. The CLUSTAN statistical package was used in studying the relative clustering of these elements for all the core levels. The resulting dendrograms from Vards nethod is suggestive of segregation and possible enrichments at some of the cores, due to contamination of the river bed. It is suspected that the contamination of some of the cores of the the river bed by primordial elements like uranium and thorium could be attributed to the high use of phosphate fertilizers by farmers cultivating the river banks. Data from this work strongly shows a disparity between th...

Speciation of arsenic and chromium in the leachate from chromated copper arsenate (CCA) type C treated southern pine (Pinus spp.)

Abstract A 558-h laboratory leaching test (AWPA E-11) was carried out on both commercially and laboratory chromated copper arsenate (CCA) type C-treated southern pine. Arsenic, chromium, and copper concentrations in the leachate collected were examined. Leaching of chromium and copper from CCA-treated wood cubes were nearly undetectable using flame atomic absorption spectroscopy after 174 and 366 h, respectively. Less than 10% of the total chromium in the leachate was present as hexavalent chromium [Cr(VI)] after leaching for 30 h. Selective ion-exchange chromatography was used to speciate arsenic in the leachate. In the first 270 h, approximately 70–90% of the total arsenic in the leachate was inorganic pentavalent arsenic [As(V)] and 10–30% was inorganic trivalent arsenic [As(III)].

Target Sites: Endocrine

Publisher Summary Many environmental factors, including the light cycle, temperature, naturally occurring ingredients in food, and anthropogenic pollutants, interact with the endocrine system and influence hormone production. Substances with the ability to interfere with hormone levels in the endocrine system, however, do not necessarily pose any health risk for humans and other organisms. The endocrine system has the capacity to tolerate moderate external challenges by evoking the adaptable control/feedback mechanisms, thus maintaining functional homeostasis of the body. However, deleterious health effects could occur when the control mechanisms of equilibrium are overwhelmed by excessive amounts of exposure to endocrine disruptors. Endocrine dysfunction could result from having either an excessive or insufficient amount of hormone production or failure to induce proper cellular responses. Excessive amounts of hormones may be caused by overproduction, rapid release from storage, decreased rate of metabolism or decreased excretion, while insufficient amount of hormone production may be caused by decreases in hormone synthesis or release, increased rate of metabolism or rapid excretion. Cellular injury of endocrine organs and altered enzymatic activities of hormone synthesis and metabolism could be the underlying etiology of endocrine toxicity. Endocrine dysfunction may also result from exposure to substances with structures similar to hormones that are capable of binding to receptors, thus either mimicking the function of a hormone or inhibiting the function of the normal hormone–receptor complex.