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PubMed2004

Phthalate-induced Leydig cell hyperplasia is associated with multiple endocrine disturbances.

The possibility that exposures to environmental agents are associated with reproductive disorders in human populations has generated much public interest recently. Phthalate esters are used most commonly as plasticizers in the food and construction industry, and di-(2-ethylhexyl) phthalate (DEHP) is the most abundant phthalate in the environment. Daily human exposure to DEHP in the U.S. is significant, and occupational and clinical exposures from DEHP-plasticized medical devices, e.g., blood bags, hemodialysis tubing, and nasogastric feeding tubes, increase body burden levels. We investigated the effects of chronic exposures to low environmentally relevant DEHP levels on testicular function. Our data show that prolonged exposures to this agent induced high levels of the gonadotropin luteinizing hormone and increased the serum concentrations of sex hormones [testosterone and 17beta-estradiol (E2)] by >50%. Increased proliferative activity in Leydig cells was evidenced by enhanced expression of cell cycle proteins, as determined by RT-PCR. The numbers of Leydig cells in the testis of DEHP-treated rats were 40-60% higher than in control rats, indicating induction of Leydig cell hyperplasia. DEHP-induced elevations in serum testosterone and E2 levels suggest the possibility of multiple crosstalks between androgen, estrogen, and steroid hormone receptors, whereas the presence of estrogen receptors in nonreproductive tissues, e.g., cardiovascular system and bones, implies that the increases in serum E2 levels have implications beyond reproduction, including systemic physiology. Analysis of the effects of phthalate exposures on gonadotropin and steroid hormone levels should form part of overall risk assessment in human populations.

Animals↗
PubMed2005

Identifying the public's knowledge and intention to use human cloning in Greek urban areas.

PURPOSE: The understanding of the public's knowledge on human cloning (HC) and its acceptability are considered important for the development of evidence-based policy making. The aim of this research study was to investigate the demographic and socioeconomic variables that affect the public's knowledge and intention to use HC in urban areas of Greece. Additionally, the possible association of religiousness with the knowledge and the intention to use HC were also investigated. METHODS: Individual interviews were conducted with 1020 men and women of urban areas in Greece. Stratified random sampling was performed to select the respondents. Several scientists, experts in HC, evaluated the content of the instrument initially developed. The final questionnaire was consequently the result of a pilot study. RESULTS: Almost half of the respondents (51.5%) believed that "HC is a sort of in vitro fertilization" and 42.9% that "it has already been applied to human being." They were not aware that "the cloned fetus grows in the woman's uterus" (41.5%) and that "HC could regenerate human organs" (41.7%). The acceptability of human cloning for the cure of terminal diseases and transplantation need is very high (70.7% and 58.6%, respectively). The public's intention to have recourse to cloning on the grounds of "bringing" back to life a loved person or because of reproductive disorders was reported as desire by 35% and 32.5%, respectively. The occupational category (scientists, self-employed, and artists), the Intention to use HC, and the number of children are highly significant predictors of valid knowledge about HC. Low rates of church attendance appeared to relate with high reported Intention to use HC, and increasing scores of valid knowledge about HC increased the public's Intention to use HC. CONCLUSIONS: A number of specific demographic and socioeconomic characteristics and high scores of knowledge provide a persuasive justification in demonstrating intention toward HC. The current study suggests that these findings should receive further attention by policymakers and scientists within the Greek context.

Adult↗
PubMedDate not supplied

Interactions between endosulfan and dieldrin on estrogen-mediated processes in vitro and in vivo.

There is growing concern that estrogenic chemicals, both natural and human-made, may be causing a variety of reproductive disorders in wildlife and human populations. Recent in vitro data suggest that the interaction between some weakly estrogenic organochlorines, dieldrin, endosulfan, toxaphene, and chlordane, causes a synergistic increase in their estrogenic potency, an effect due to joint action on estrogen receptors (ER). As these studies were conducted using models of estrogen action derived from cells that are not physiologically controlled by estrogens, the relevance of these findings to human health are not clear. The present studies were conducted to examine the interaction between endosulfan and dieldrin in the activation of ER in or extracted from mammalian cells. Endosulfan and dieldrin showed no synergism in displacing 3H-E2 from rat uterine ER or in inducing the proliferation of MCF-7 breast cancer cells, an estrogen-dependent response. Furthermore, endosulfan (0.1 mg per animal per d) or dieldrin (0.1 mg), alone or in combination, injected intraperitoneally daily for 3 d, did not stimulate any uterotrophic activity nor had any effect on pituitary prolactin or other endocrine-related endpoints in immature female rats. These studies demonstrate that these weakly estrogenic compounds do not interact in a synergistic fashion in binding to ER or in activating ER-dependent responses in mammalian tissues or cells. Thus, these results suggest that coexposure to these weakly estrogenic environmental contaminants likely will not cause human reproductive toxicity related to estrogen action.

Animals↗
PubMed2002

Treatment of unobserved oestrus in a dairy cattle herd with low oestrous detection rate up to 60 days post-partum.

The efficiency of treatments for unobserved oestrus and their effect on the reproductive performance of a dairy cattle herd with low oestrous detection rate till 60 days post-partum (dpp), attributed to the declivous and slippery concrete floor were investigated. The herdsman requested advice in order to improve the mean days open of the herd, but no investments were allowed because a new unit was about to be built. Due to the low oestrus detection rate of the herd, the breeding policy was to inseminate at the first detected post-partum oestrus. Cows were examined at 20-30 dpp to assess uterine involution, ovarian activity and prevalence of reproductive disorders and, at 60 dpp if no previous oestrus was detected. Each examination included palpation per rectum, ultrasound scanning and collection of a blood sample for plasma progesterone (P4) measurement. Cows with unobserved oestrus till 60 dpp were allocated either to a treatment group (n=139) or to a control group (n=139). Three treatments were used: (a) injection of PGF(2 alpha) (PG) upon detection of a corpus luteum (CL; n = 30), cows not observed in oestrus being re-injected 11-12 days later. AI was at oestrus; (b) PRID (n=35) or Crestar (n=74) devices kept in situ for 12 and 9 days, respectively, were associated to an injection of PG and of equine chorionic gonadotrophin (eCG) at device removal. Cows were double-fixed time-inseminated at 48 and 72 h after device removal. All treated cows were examined at 48-72 h after treatment to confirm oestrus. The percentage of cows detected in oestrus up to 60 dpp remained unchanged through the trial (35 and 47% for years before intervention: 1994-95; 51 and 48% for years of intervention: 1996-97). In contrast, the oestrous detection rate was high both in treated (93%) and control (100%) cows. This possibly resulted from an improvement in the oestrous detection efficiency of the herd's personnel and from examination of cows at 48-72 h after treatment. Treated and control cows had identical conception rate (CR; 36 and 37%, respectively) and reproductive performance. However, the mean days open of the herd in 1996 was significantly improved in comparison with previous years (mean +/- SEM: 134 +/- 6, 126 +/- 5, 110 +/- 4 and 114 +/- 5 days, for years 1994, 1995, 1996 and 1997, respectively, p < 0.05, ANOVA). Conception rate to AI up to 40 dpp was significantly reduced, compared with the period between 60 and 100 dpp but, mean days open were significantly improved in cows inseminated up to 60 dpp, compared with thereafter (p < 0.05).

Animals↗
PubMed2006

Detection of chlamydiae in boar semen and genital tracts.

Chlamydiae cause abortion and reproductive disorders in sows. Although organisms can infect the male genital tract, little is known about the disease situation in boars. Hence, we examined the prevalence of chlamydial infection in semen and genital tracts of boars. Samples collected from Swiss boars (group A: n=42), and boars from Germany (group B: n=39) were examined by bacteriology, LPS-ELISA, immunohistochemistry (IHC) and polymerase chain reaction (PCR). The latter methodology involved use of three PCR assays including 16Sig rDNA, IGS-S (intergenic spacer 16S/23S-Short) and IGS-L (intergenic spacer 16S/23S-Long) PCR for comparison methods. PCR sensitivity and the presence of potential PCR inhibitors were determined by spiking semen with Chlamydophila (Cp.) abortus DNA. Detection limits of the 16Sig and IGS-S PCR were 10 templates, while the IGS-L PCR was less sensitive (100 templates). Of 25 semen samples that were collected from group A, one semen sample was positive for Cp. psittaci and two were positive for Chlamydia-like organisms by 16Sig PCR. Screening of sera from Swiss boars revealed three animals with positive reactions in the LPS-ELISA, although we failed to detect chlamydiae within organs of these or sera-negative animals by IHC or IGS-S PCR. In group B, 10 ejaculates were positive for Chlamydia (C.) suis and two were positive for Chlamydia-like organisms by 16S PCR. The identification of DNA from Chlamydia-like organisms in semen from both groups of boars was surprising and a role for these bacteria in reproductive diseases requires further assessment. In conclusion, the prevalence of chlamydial infection was low in group A animals indicating that venereal transmission may not be significant for Chlamydia-associated reproductive diseases in pigs, although rare cases may occur.

Animals↗
PubMed2002

Predictors of ovulatory failure in women with epilepsy.

Women with epilepsy (WWE) are at increased risk for reproductive disorders. This study was designed to evaluate whether WWE are more likely to have anovulatory cycles and to assess the relative association of the epilepsy syndrome category and antiepileptic drugs (AEDs) to ovulatory dysfunction. Subjects included women aged 18 to 40 years not receiving hormones. Women without epilepsy (23 controls) and women with localization-related epilepsy (LRE, n = 59) or idiopathic (primary) generalized epilepsy (IGE, n = 35) receiving either a cytochrome P450 enzyme (cP450) inducing AED (carbamazepine, phenytoin, and phenobarbital), a cP450 inhibiting AED (valproate), or an AED that does not alter cP450 enzymes (lamotrigine and gabapentin) in monotherapy for 6 months or more were followed for three menstrual cycles. A transvaginal ovarian ultrasound was obtained. Endocrine and metabolic variables were measured and luteinizing hormone sampled over 8 hours on days 2 to 5 of one cycle. Anovulatory cycles occurred in 10.9% of cycles in controls, 14.3% of cycles with LRE, and 27.1% of cycles with IGE. Of women using valproate currently or within the preceding 3 years, 38.1% had at least one anovulatory cycle in contrast with 10.7% of women not using valproate within the preceding 3 years. Predictors of ovulatory failure included IGE syndrome, use of valproate currently or within 3 years, high free testosterone, and fewer numbers of luteinizing hormone pulses, but not polycystic-appearing ovaries. WWE are more likely to experience anovulatory menstrual cycles and the effects of epilepsy syndrome, and AED therapy may be additive. Women with IGE receiving valproate were at highest risk for anovulatory cycles, polycystic-appearing ovaries, elevated body mass index, and hyperandrogynism. WWE with anovulatory cycles may have no other signs of reproductive dysfunction. Therefore, clinicians must be alert to this potential complication of epilepsy.

Adolescent↗
PubMed1996

Morphometric study on the uterine horn and thyroid gland in hypothyroid, and thyroxine treated hypothyroid rats.

A wide range of reproductive disorders such as irregular menstruation and frank infertility is found in women with hypothyroidism. Most research done on these patients has focused on steroid and gonadotropin hormone profiles, whilst there has been little work on uterine morphology. Studies on hypothyroid animals have also demonstrated increases in fetal wastage, but there have been few studies of uterine structure in the hypothyroid rat. The present study has used hypothyroid Wistar rats as a model for investigating the effects of hypothyroidism on uterine structure. Three groups of Wistar rats were studied. One was made hypothyroid with methimazole (MMI), the 2nd was also made hypothyroid with methimazole but in addition the rats were simultaneously given daily thyroxine intraperitoneally (MMI + T4), and the 3rd was an untreated euthyroid group (control). Daily vaginal smears were obtained from rats in all 3 groups. All rats were aged 6 wk at the start of treatment and were killed after a further 6 wk. Uterine horns were removed and studied. Systematic random transverse sections were obtained from the proximal, middle, and distal regions of the horn and subjected to morphometric analysis. Difference between regions was assessed using 2-way analysis of variance. Absolute volume of endometrium in the uteri of hypothyroid rats was reduced by 45.1% (P < 0.05), whilst that of the muscle layer was decreased by 33.6% (P < 0.05). The cross-sectional area and absolute volume of the uterine horns were also reduced in hypothyroid animals (P < 0.05). In hypothyroid rats given thyroxine (MMI + T4) all variables increased significantly above those of hypothyroid rats. These changes suggest that hypothyroidism has an effect on uterine structure, which demonstrably improves under exogenous thyroxine administration. The observed structural changes might well play a significant role in the reproductive difficulties observed during hypothyroidism.

Analysis of Variance↗
PubMed1990

Cytokines act within the brain to inhibit luteinizing hormone secretion and ovulation in the rat.

Alterations of immune activity are often accompanied by reproductive disorders. Because interleukins mediate the host's response to immune activation, we first examined the effect of the central injection of several lymphokines on LH secretion by gonadectomized rats. We then studied the ability of the most potent lymphokine in this system, interleukin-1 beta (Il-1 beta), to interfere with the proestrous LH surge and ovulation in the intact female rat as well as the dependence of this effect on the activation of opiate receptors. Finally, we investigated the possibility that increased brain levels of Ils, as induced by the central administration of a bacterial endotoxin, might also alter the normal ovulatory process. After intracerebroventricular (icv) injection, Il-1 beta, Il-6, and tumor necrosis factor all lowered plasma LH levels in castrated rats. On a molar basis, Il-1 beta was the most potent inhibitor of LH secretion. In gonadectomized animals, 2.5 and 10 ng Il-1 beta administered icv significantly (P less than or equal to 0.01) decreased plasma LH levels for 6 h, while the effect of 40 ng lasted up to 12 h. By contrast, FSH secretion was only measurably altered by 40 ng Il-1 beta 8 and 12 h posttreatment. In intact cycling female rats, icv injection of 40 ng Il-1 beta or 400 ng Il-1 alpha at 0830 h on the morning of proestrus significantly (P less than 0.01 and P less than 0.05, respectively) interfered with the proestrous surge of LH. In contrast, the peripheral administration of either lymphokine was without measurable effect. Centrally injected Il-1 beta (40 ng at 0830 h on proestrus) also blocked ovulation in most animals, while a dose of 25 ng injected iv was ineffective. Finally, we observed that the icv injection of endotoxin (a lipopolysaccharide), also interfered with ovulation. The possible involvement of opiate-dependent pathways in mediating the inhibitory action of Il-1 beta on reproductive processes was tested by implanting naloxone pellets 16-24 h before lymphokine treatment. The pellets, which released 200, 400, or 800 micrograms naloxone/h (corresponding to approximately 0.6, 1.32, or 2.64 mg/kg BW.h), had no effect on ovulation by themselves. When given before icv Il-1 beta, all naloxone regimens countered the effect of the cytokine, with the 800-micrograms/h dose restoring ovulation in eight of nine rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1999

Effect of porcine reproductive and respiratory syndrome virus (PRRSV) on alveolar lung macrophage survival and function.

Porcine reproductive and respiratory syndrome virus (PRRSV) recently emerged as an important cause of reproductive disorders and pneumonia in domestic pigs throughout the world. Acute cytocidal replication of PRRSV in alveolar lung macrophages causes the acute pneumonia; however, it remains largely unresolved whether there may also be a predisposition to longer-term local immunodeficiency in the PRRSV-convalescent lung. We applied various flow cytometric techniques to study the interplay between PRRSV replication and macrophage viability/function in pure cultures of porcine alveolar lung macrophages. Monitored by flow cytometric detection of intracellular PRRSV nucleocapsid protein, acute (24 h post infection) PRRSV replication did not impede the ability of alveolar macrophages to ingest fluorescently labelled Escherichia coli. At 48 h post infection, PRRSV-induced cytotoxicity (quantitated by flow analysis of cell size and membrane integrity) led to 40% reduction in the total number of phagocytozing cells. However, viable/uninfected macrophages in PRRSV-infected cultures exhibited normal phagocytic ability at 48 h, indicating that no soluble phagocytosis-suppressive mediators were induced by PRRSV infection in this system. In short, in our minimal system containing only a single cell type, phagocytosis-suppressive effects of PRRSV infection were detected, that acted at the culture level by reducing the total number of alveolar lung macrophages.

Animals↗
PubMed2005

What have we learned about gonadotropin function from gonadotropin subunit and receptor knockout mice?

A number of biochemical and physiological studies elucidated the roles of pituitary and placental glycoprotein hormones. Advances in the past two decades in manipulating the mouse genome by random or site-specific mutagenesis have heralded a new dimension to our understanding of the biology of gonadotropins. It is now possible to model many human reproductive disorders involving gonadotropins/gonadotropin-signaling in the mouse. Mutant mice selectively lacking either FSH or LH or their cognate receptors have been generated. The gonadotropin ligand and the corresponding receptor knockout mice mostly phenocopy each other. Analyses with these genetic models confirmed earlier physiological studies; in addition they also revealed novel roles for gonadotropins previously unrecognized. While FSH action seems dispensable for male but not female fertility, absence of LH causes infertility in both the sexes. While Sertoli cell number and germ cell carrying capacity of the Sertoli cells in compromised in FSH mutants, both somatic and germ cell lineages are affected in the LH mutants resulting in complete male infertility. FSH mutant females demonstrate a preantral stage block in folliculogenesis and FSH alone is not sufficient to promote full folliculogenesis in the absence of LH. Pre-ovulatory stage follicles do not form and most of the follicles undergo apoptosis in the absence of LH. Many extra-gonadal phenotypes have been described for the receptor knockout mice and whether these bear any resemblances to those in patients with similar inactivating mutations in the receptors for FSH and LH remains an open question. Thus the in vivo models will continue to have a significant impact in understanding gonadotropin physiology and pathophysiology and serve as novel genetic tools to study signaling mechanisms in the gonads.

Animals↗
PubMed1997

Neonatal treatment with tamoxifen causes immediate alterations of the sexually dimorphic nucleus of the preoptic area and medial preoptic area in male rats.

Tamoxifen is an antiestrogen widely used for the treatment of breast cancer. Current evolutions in preventive strategies to include healthy premenopausal women warrant the study of its developmental toxicity. Perinatal treatment of male rodents with tamoxifen caused reproductive tract lesions and sexual behavior deficits similar to those induced by diethylstilbestrol (DES). Those abnormalities could originate, at least in part, from lesions of the hypothalamic-pituitary axis. The initial alterations caused by tamoxifen in the hypothalamic medial preoptic area (MPOA) and sexually dimorphic nucleus of the preoptic area (SDN-POA) were studied in 6-day-old male rat pups treated with 100 micrograms tamoxifen (group 1), 1 microgram DES (group 2) or vehicle (group 3) from PN1 to 5. In situ hybridization was performed to analyze the expression of the GAP-43 gene, a marker of neuronal differentiation, and morphometry was used to study the neuronal density in the SDN-POA and MPOA and the volume and number of neurons in the SDN-POA. Tamoxifen reduced severely the volume and neuron numbers in the SDN-POA (46.1% and 47.8% of controls, respectively). The neuronal density of the MPOA was not modified. GAP-43 gene expression was decreased as demonstrated by a greater percentage of unlabeled neurons (grade 0) mirrored by a lesser percentage of intensely labeled ones (grade 2) in the SDN-POA and MPOA. In contrast to the effects of the antiestrogen, DES did not affect the above endpoints. These data indicated that developmental exposure of male rat pups to tamoxifen-induced immediate neuronal loss in one and altered differentiation in two hypothalamic areas crucial to reproduction. How those initial alterations contribute to the pathogenesis of the reproductive disorders observed in the adult male needs further investigation.

Animals↗
PubMed2000

Five meters of H(2)O: the pressure at the urinary bladder neck during human ejaculation.

BACKGROUND: There are no data in the literature on pressure changes in the prostatic urethra during ejaculation. In healthy men, it has always been postulated that there must be a pressure gradient in order to prevent retrograde ejaculation, but scientific proof for that is pending. METHODS: In five healthy male volunteers, the pressure profile in the prostatic urethra was registered during ejaculation, using a 10 French balloon catheter with 16 pressure channels. The channels were arranged in pairs at 5-mm intervals, beginning just below the balloon at the bladder neck and extending down to the external urethral sphincter. RESULTS: In the proximal part of the prostatic urethra, a pressure of up to 500 cm of H(2)O was measured in all subjects. Contrary to that, pressures did not exceed 400 cm of H(2)O distally to the verumontanum. CONCLUSIONS: A novel method to register the pressure profile in the lower urinary tract during ejaculation (ejaculomanometry) is presented. This study adds to the knowledge of the normal physiology of reproductive function and may be useful in the evaluation of male sexual and reproductive disorders.

Adult↗
PubMed2003

Effects of experimental diabetes on the structure and ultrastructure of the coagulating gland of C57BL/6J and NOD mice.

Diabetes mellitus can lead to reproductive disorders that in turn result in weakened fertility brought about by morphofunctional changes in the testes and accessory sex glands. However, doubts persist concerning the basic biology of the secretory epithelial cells and the stroma of the coagulating gland of diabetic mice. Thus, the objective of the present study was to analyze the histological and ultrastructural changes associated with stereology of the coagulating gland of mice with alloxan-induced diabetes, and of spontaneously diabetic mice. Sixteen mice of the C57BL/6J strain, and eight non-obese diabetic (NOD) mice were used. The animals were divided into three groups: 1) control (C), 2) alloxan diabetic (AD), and 3) NOD. Thirty days after the detection of diabetic status in group 2, all of the animals were killed and then perfused with Karnovsky's solution through the left cardiac ventricle. The coagulating gland was then removed and processed for morphometric study by light microscopy and electron microscopy. The results showed thickening of the stroma, atrophy of secretory epithelial cells, and disorganization of the organelles involved in the secretory process in both NOD and alloxan-induced mice. Thus, it may be concluded that the coagulating gland suffered drastic morphological changes, and consequently impaired glandular function, in the presence of diabetes mellitus type I in both NOD and AD mice.

Animals↗
PubMed2003

Estrogenic endocrine disruptive components interfere with calcium handling and differentiation of human trophoblast cells.

During development, calcium (Ca) is actively transported by placental trophoblasts to meet fetal nutritional and the skeletal mineralization needs. Maternal exposure to estrogenic pesticides, such as 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane (DDT) and methoxychlor (MTC), has been shown to result in reproductive disorders and/or abnormal fetal development. In this study, we have examined the effects of exposure of trophoblastic cells to MTC and DTT, in comparison to 17beta-estradiol (E2) and diethylstilbestrol (DES), to test the hypothesis that cellular Ca handling is a target for these endocrine disruptive components. Treatment with DDT, MTC, DES, or E2 increased cellular Ca uptake, and the expression of trophoblast-specific human Ca binding protein (HCaBP) was down-regulated by both MTC and DDT. Treatment with MTC, DDT, and DES inhibited cell proliferation, induced apoptosis, and suppressed expression of several trophoblast differentiation marker genes. These effects were reversed by overexpression of metallothionein IIa, a gene highly responsive to cadmium and other metals. These results strongly suggest that trophoblast Ca handling functions are endocrinally modulated, and that their alteration by candidate endocrine disruptors, such as MTC and DDT, constitutes a possible pathway of the harmful effects of these components on fetal development.

Adenosine Triphosphatases↗
PubMed1999

2-Bromopropane causes ovarian dysfunction by damaging primordial follicles and their oocytes in female rats.

Ovarian dysfunction induced by 2-bromopropane (2-BP) has been described in female factory workers and experimental animals. However, the underlying mechanism is still unclear. To establish the reproductive target site and define mechanisms of 2-BP toxicity in adult female rats, we examined the effects of different doses and duration of exposure to 2-BP in female rats. In the dose-dependent experiments, female rats were exposed to 2-BP at 100, 300, or 1000 ppm or fresh air (n = 9 each) in exposure chambers for 8 h/day for 9 weeks. In the time-course experiments, female rats were exposed to 2-BP at 3000 ppm for 8 h (n = 7 each). The rats were then euthanized 1, 3, 5, and 17 days after exposure. Differential follicle counts and in situ terminal deoxynucleotidyl transferase assay were used to evaluate 2-BP effect on primordial, growing, and antral follicles. Exposure to 2-BP at 300 and 1000 ppm produced a significant reduction in the percentage of primordial, growing, and antral follicles in a dose-dependent manner. Significant reduction in the percentage of primordial follicles at 17 days after exposure was observed in time-course experiments. Exposure to 2-BP at 3000 ppm for 8 h resulted in histological changes in primordial follicles complex at 5 and 17 days after exposure. These changes consisted of distortion of the symmetry of oocytes and their nuclei at Day 5 after exposure and appearance of eccentric pyknotic cells and shrinkage of oocyte nuclei at Day 17 after exposure. In situ end labeling showed increased numbers of apoptotic oocytes and granulosa cells in primordial follicles at Days 5 and 17 after exposure. Our results suggested that ovarian dysfunction induced by 2-BP was caused by the destruction of primordial follicle and its oocyte due to the induction of apoptosis. Our studies also show that the follicle differential count is a more sensitive method than the vaginal smear in monitoring the female reproductive disorders induced by 2-BP.

Animals↗
PubMed2001

Evidence for endocrine disruption in perch (Perca fluviatilis) and roach (Rutilus rutilus) in a remote Swedish lake in the vicinity of a public refuse dump.

A two-year study on perch (Perca fluviatilis) in Lake Molnbyggen, Sweden, located in a pristine area but with a public refuse dump in the vicinity, has been conducted. The mechanistic approach through a set of biomarkers during the first year included age, condition, somatic growth, liver, gonad, and spleen weights, and a number of other physiological variables, in addition to ethoxyresorufin O-deethylase, glutathione-S-transferase, glutathione reductase, catalase, and the formation of DNA adducts in the liver. Perch from the uncontaminated Lake Djursjön, located in a neighboring drainage area, were used as reference fish. The most pronounced effect was a 80% reduction in the gonadosomatic index (GSI) for females and a corresponding 36% reduction in males. Fin erosion and shallow open sores were also frequently observed. Biomarkers and later chemical analysis employed indicated that exposure to well-known environmental pollutants was low, suggesting that less well-known antrophogenic substances are responsible for the effects observed in perch from Lake Molnbyggen. During the second year, roach (Rutilus rutilus) of both sexes were also included in this study. In addition, aromatase (P450arom) activity in the brain and testosterone and 17beta-estradiol levels in blood plasma were analyzed. Only one-fourth of the female perch were found to be sexually mature, which was associated with decreased GSI, lower P450arom activity, and reduced circulating levels of steroids. The reproductive disorders observed indicates disturbed endocrine function(s), arresting the majority of the female perch in a sexually nonreproducible immature stage. This novel study is the first to report evidence for endocrine disruption in wild populations of fish living in a lake exposed to leakage water from a public refuse dump.

Animals↗
PubMed2002

Caffeine enhances the calcium-dependent cardiac mitochondrial permeability transition: relevance for caffeine toxicity.

Caffeine (1,3,7-trimethylxanthine), a compound present in beverages such as tea and coffee, is known to be toxic at high concentrations. Some of the observed clinical conditions include cardiovascular disease and reproductive disorders, among others. The possible toxic effects of caffeine on heart mitochondria are still poorly understood. The influence of caffeine on the mitochondrial permeability transition has not been clarified so far. The objective of this study was to investigate whether caffeine, at toxic concentrations, had any stimulating effect on the permeability transition of heart mitochondria isolated from Wistar rats, as well as whether it influenced mitochondrial respiratory parameters. Our results show that caffeine reduced mitochondrial ability to accumulate calcium by increasing the susceptibility of heart mitochondria to the opening of the transition pore. Caffeine not only hindered mitochondrial capacity to recover membrane potential after calcium addition but also increased the rate of calcium-dependent mitochondrial swelling and calcium-induced calcium release. The increased swelling was also observed in nonenergized mitochondria. Caffeine also showed a complex array of effects on heart mitochondrial bioenergetics, as evaluated by respiratory parameter measurements. We observed an increase in state 4 respiration and a depression in state 3 respiration, although no effect was observed on succinate-sustained mitochondrial membrane potential in the absence of calcium. Our work may be relevant to cardiovascular problems linked to caffeine toxicity and also to in vitro experiences involving caffeine-induced calcium release from the sarcoplasmic reticulum and uptake by mitochondria.

Animals↗
PubMed1988

Variables affecting toxicity of human sera in mouse embryo cultures.

It has been reported that sera from women with reproductive disorders can inhibit mouse embryo development. While performing tests on this subject in our laboratory, two unexpected variables were identified that can influence the effect of human serum on mouse embryo cultures. In a standard embryo culture system in which heat-inactivated sera (10% final concentration) were added to two-cell mouse embryos and percentage blastocyst development was scored after 4 days, sera that had been collected into standard clinical Monoject blood collection red-stopper tubes were significantly more embryotoxic than sera collected from the same subjects into 15-ml Falcon centrifuge tubes (P less than 0.005). Furthermore, we observed that sera from laboratory personnel that worked with mice often inhibited mouse embryo development. To study this effect further, sera were collected from five fertile individuals who were routinely exposed to mice and from fertile women with no previous exposure to rodents. Sera from the mouse-exposed group were significantly more inhibitory than sera from the nonexposed control group (P less than 0.005). The effect was observed in the ammonium sulfate-precipitated immunoglobulin fraction of the mouse-exposed group's sera, and high titers of antibodies reactive with mouse spleen cells were detected in sera and immunoglobulin fractions from this group by enzyme-linked immunosorbent assay (ELISA). Embryotoxic activity was neutralized by absorption with mouse lymphocytes, but not with rabbit or human lymphocytes, suggesting that a heterophilic antimouse antibody is the factor responsible for this effect. These data emphasize the importance of including extensive controls in experiments addressing toxic effects of human sera on mouse embryos.

Animals↗