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Biomedical subjects

J J Tarín

Publications and source records attributed to J J Tarín.

At least 19 recordsLinked to original sources
PubMed2006

Alterations in the phenotype and function of immune cells in ovariectomy-induced osteopenic mice.

BACKGROUND: Within the last few years, much evidence has been presented on the involvement of the immune system in certain types of bone loss, such as activated T cells in rheumatoid arthritis and in periodontitis. Estrogen deficiency induces bone loss; however, how this deficiency affects the immune system has not been sufficiently studied. METHODS: To evaluate the effects of estrogen withdrawal on the status and functionality of the immune system, mice were ovariectomized or sham-operated, and 5 weeks after surgery, when osteopenia had developed, several parameters were analysed in spleen and in bone marrow. We analysed bone turnover, cell phenotype by flow cytometry, cell function by cell proliferation assays, and the expression of several genes related to the process. RESULTS: Five weeks after ovariectomy, augmented osteoclastogenesis persisted in the bone marrow. In addition, the ovariectomized mice had more B-cells and CD3+ T-cells expressing the receptor activator of NF-kappaB ligand (CD3+/RANKL+). The ovariectomized mice had lower serum alkaline phosphatase activity, a normal amount of T cells, lower percentages of CD11b+ and CD51+ cells in the bone marrow, and a lower serum interferon-gamma level compared with sham-operated controls. CONCLUSIONS: The data suggest that, 5 weeks after ovariectomy, bone turnover remains imbalanced, with increased osteoclastogenesis and a decreased rate of bone formation. Moreover, there is an increase in B-cell formation, with normal and decreased percentages of T cells and myelomonocytic cells (CD11b+), respectively, in the bone marrow. Decreased serum interferon-gamma levels could be involved in the increased osteoclastogenesis found in the present work.

Alkaline Phosphatase↗
PubMed2005

Progestogens stimulate prostacyclin production by human endothelial cells.

BACKGROUND: The effects of progestogens on endothelial physiology are poorly studied. Prostacyclin is a potent vasodilator synthesized by two isoforms of cyclooxygenase (COX) in endothelium. We examined the effects of two clinically used progestogens, progesterone and medroxyprogesterone acetate (MPA), on prostacyclin production by cultured human umbilical vein endothelial cells (HUVEC) and the possible role of progesterone receptors and both COX enzymes. METHODS: Cells were exposed to 1-100 nmol/l of either progesterone or MPA and prostacyclin production was measured in culture medium. RESULTS: Both progestogens significantly increased prostacyclin release in a time- and dose-dependent manner, being higher than control after 24 h. Progesterone and MPA, both at 10 nmol/l, increased mRNA expression and protein content of both COX. All these effects were mediated through progesterone receptor activation, since they were abolished by treatment of cells with the progesterone receptor antagonist RU-486. Selective inhibitors of COX-1 and -2 (SC-560 and NS-398 respectively) reduced basal prostacyclin release, and eliminated increased production in response to progestogens. In combination with estradiol, progestogens had an additive effect without eliminating estradiol-induced prostacyclin production. CONCLUSIONS: Our results support the hypothesis that progesterone and MPA increased HUVEC prostacyclin production in a progesterone receptor-dependent manner, by enhancing COX-1 and COX-2 expression and activities.

Cells, Cultured↗
PubMed2004

Effect of delayed breeding on the reproductive performance of female mice.

The aim of the present study was to determine, in the mouse, whether maintaining females as virgins until an advanced reproductive age was associated with decreased reproductive performance and reproductive lifespan compared with females of the same age that were first mated with males at an earlier reproductive age. Randomly selected virgin hybrid (C57BL/6JIco female x CBA/JIco male) female mice were housed individually with a randomly selected 12- to 14-week-old hybrid male either at the age of 28 weeks (normal breeding group; n = 20) or 51 weeks (delayed breeding group; n = 23) for the rest of their reproductive life. Females were checked once daily to determine the day of parturition and to record the litter size and gender of pups at birth for each consecutive litter. At weaning, offspring were weighed and killed. Delayed breeding was associated with smaller litter sizes, both at birth and at weaning, a higher bodyweight of pups at weaning, a higher percentage of litters with at least one newborn pup cannibalised, earlier cessation of female reproductive life and a higher mortality rate of dams during the breeding period. These results show that delayed breeding in the mouse is associated with decreased reproductive performance and a shorter reproductive lifespan compared with females bred at an earlier reproductive age.

Age Factors↗
PubMed2003

Bone turnover markers and PTH levels in surgical versus natural menopause.

In order to assess similarities and differences in women that suffer surgical versus natural menopause, a series of bone, clinical, and biochemical parameters was assayed in a clinical sample of 35 women with surgical menopause and 112 women with natural menopause. Biochemical parameters included hormones [parathyroid hormone (PTH) and the sex steroids estradiol and testosterone] and several markers of bone turnover measured in urine (N-telopeptide and calcium/creatinine ratio) or serum (osteocalcin, total alkaline phosphatase, total and ionic calcium, phosphate, and magnesium). In addition to type of menopause, women were divided by years since menopause (ysm </= 2 or >2). To detect differences and relationships between variables, ANOVA, ANCOVA, and linear regression analyses were used. Only N-telopeptide, one resorption marker, was significantly affected by the variable years since menopause </=2 or >2 ( P <0.01), but not by type of menopause. The age-corrected level of PTH was significantly decreased in the surgical menopause group ( P < 0.05). In conclusion, type of menopause did not impose significant differences in bone turnover markers. PTH, one powerful resorption hormone, was diminished in surgical menopause.

Absorptiometry, Photon↗
PubMed2002

Oral administration of pharmacological doses of vitamins C and E reduces reproductive fitness and impairs the ovarian and uterine functions of female mice.

This study aims to ascertain whether oral administration of pharmacological doses of Vitamins C and E has any detrimental effect on reproductive fitness of female mice. We fed hybrid female mice from the first day of weaning a standard diet supplemented or not supplemented with pharmacological doses of Vitamins C and E. At the age of 28 weeks, we individually caged females with a male for the rest of their reproductive life. We performed a series of mating experiments to ascertain the number of oocytes ovulated and the potential for embryo development in vitro to the blastocyst stage and in vivo to Day 12 of gestation. The antioxidant diet decreased the frequency of litters, litter size, total number of offspring born and survival of male pups to weaning. This effect was associated with lower number of corpora lutea in the left ovary, decreased percentage of viable fetuses, and higher number of fetal resorptions in the left uterine horn when compared to the control group. The strategy of supplementing the diet with antioxidant vitamins to prevent the age associated decrease in reproductive potential should not be implemented in human beings until a safe and efficient diet is designed.

Animals↗
PubMed2002

Effect of dietary supplementation with a mixture of Vitamins C and E on fertilization of tertiary butyl hydroperoxide-treated oocytes and parthenogenetic activation in the mouse.

The present study aims to analyze the effect of dietary supplementation with a mixture of Vitamins C and E on fertilization and later development of tertiary butyl hydroperoxide (tBH)-treated mouse oocytes and on parthenogenetic activation of freshly ovulated mouse oocytes. We fed hybrid mice a standard diet supplemented or not supplemented with Vitamins C and E from the first day of weaning until the age of 12 weeks. We noted no significant effect of diet on fertilization rate, percentage of total and hatching blastocysts, total number of cells, mitotic index and percentage of apoptotic nuclei at 120 h post-insemination of oocytes incubated for 15 min in the presence of 0, 1, 5 and 10 microM tBH. Furthermore, diet did not affect the percentage of activated oocytes after treatment with Ca2+ ionophore, acid Tyrode's solution or ethanol. The percentage of parthenogenetically activated oocytes that progressed to the pronuclear stage was significantly higher in the antioxidant group. Oocytes from antioxidant females exhibited a significantly lower mitogen-activated protein kinase (MAPK) activity than oocytes from control females. We detected no significant differences between groups in M-phase-promoting factor (MPF) activity. These results show that oral administration of antioxidants decreases MAPK activity and increases the probability of reaching the pronuclear stage after parthenogenetic activation.

Animals↗
PubMed2001

The effect of oral hormone replacement therapy on lipoprotein profile, resistance of LDL to oxidation and LDL particle size.

OBJECTIVES: To disclose if oral estradiol (E(2)), alone or in combination with natural progesterone (P) or medroxyprogesterone acetate (MPA), may modify the oxidizability of low density lipoprotein (LDL), and if the effect is achieved at physiological dosages. LDL oxidizability was assessed by the resistance to oxidation by copper and by the particle size profile, since small particles have increased oxidation susceptibility. METHODS: Thirty-three women received two consecutive, two-month length doses of 1 and 2 mg/day of oral E(2). They were then randomly assigned to a fourteen-day treatment of 2 mg/day E(2) plus either 300 mg/day P or 5 mg/day MPA. A parallel group of experiments was performed on a pool of baseline plasma, where hormones were added at the desired concentration. Lipoprotein levels, resistance of LDL to oxidation, and LDL particle diameter, were measured at baseline and after each treatment. RESULTS: Estradiol reduced LDL levels and increased high density lipoprotein (HDL) and triglycerides. P abolished these changes, whereas MPA only reversed the increase of HDL. Estradiol protected LDL from oxidation in a dose-dependent manner, although only at pharmacological concentrations (1 microM or higher). Both P and MPA were inert at either physiological or pharmacological concentrations. The size of the LDL particles remained unaffected except under MPA, in which it was reduced. CONCLUSIONS: Estradiol has a protective effect against LDL oxidation, although only at pharmacological dosages. P and MPA did not limit the E(2) action. The size of the LDL particles remained unaltered after each E(2) dose, but MPA, and not P, was associated with a diminution.

Administration, Oral↗
PubMed2001

Delayed motherhood increases the probability of sons to be infertile.

PURPOSE: To ascertain whether advanced maternal age at birth is associated with offspring infertility. METHODS: A written questionnaire was completed by infertile couples attending our clinic in the presence of a researcher. RESULTS: Maternal age at birth (odds ratio 1.236, 95% CI 1.100-1.388) and birth order of all respondents and their respective siblings (odds ratio 0.551, 95% CI 0.351-0.865) were significant predictors of male infertility. The probability of a man being infertile increased as mother's age at birth increased (regression coefficient +/- standard error 0.212 +/- 0.059; P < 0.001), but decreased as birth order increased (regression coefficient +/- standard error -0.596 +/- 0.230; P = 0.010). CONCLUSIONS: Delayed motherhood may enhance the probability of sons to be infertile. The probability of a man being infertile would be greater if he comes from a small family than if he comes from a large family.

Female↗
PubMed2001

Cellular and morphological traits of oocytes retrieved from aging mice after exogenous ovarian stimulation.

The present study aims to shed light on the origin of abnormal oocytes ovulated by aged females. In order to reach this goal, cellular and morphological traits of ovulated oocytes from hybrid (C57Bl/6JIco female x CBA/JIco male) female mice retrieved after exogenous ovarian stimulation at the age of 12, 40-42, 50-52, or 57-62 wk were analyzed. Aging of female mice was associated with 1) decreased number of ovulated oocytes; 2) increased percentage of cumulus-free oocytes; 3) raised percentage of oocytes with intracellular mitochondrial aggregates; 4) reduced percentage of oocytes displaying a normal distribution of chromosomes in the metaphase-II plate; 5) increased percentage of normal oocytes exhibiting a DNA-containing polar body (PB); 6) higher percentage of oocytes with chromosome scattering; 7) increased percentage of chromosome-scattered oocytes without a DNA-containing PB and with intracytoplasmic mitochondrial aggregates; 8) raised percentage of oocytes exhibiting chromosome decondensation; 9) lower percentage of chromosome-decondensed oocytes lacking both a DNA-containing PB and intracytoplasmic mitochondrial aggregates; 10) increased percentage of abnormal/degenerated oocytes; 11) reduced percentage of abnormal/degenerated oocytes displaying cellular fragmentation; and 12) higher percentage of abnormal/degenerated oocytes with mitochondrial aggregates exhibiting no nuclear/chromosomal DNA fluorescence, cellular fragmentation, milky or dark cytoplasm, or cellular remains enclosed by the zona pellucida. Although several studies suggest aging females may ovulate aged or overripened oocytes, these data support the hypothesis that old females ovulate an increased percentage of atretic/apoptotic oocytes coming from rescued follicles that would have become atretic earlier in life.

Aging↗
PubMed1999

Two-year prospective, randomized trial comparing an innovative twice-a-week progestin regimen with a continuous combined regimen as postmenopausal hormone therapy.

OBJECTIVE: To compare compliance, symptom control, bleeding patterns, endometrial response, and lipid changes in postmenopausal women treated with transdermal E2 and a regimen of either intermittent or continuous dosing of progestin. DESIGN: Randomized, prospective study. SETTING: Menopausal Outpatient Clinic at an academic tertiary care hospital. PATIENT(S): One hundred women who had reached menopause naturally and had been amenorrheic for at least 1 year. Fifty women were randomly assigned to receive each regimen. INTERVENTION(S): All patients received 50-microg E2 patches and medroxyprogesterone acetate, either 5 mg twice per week or 2.5 mg daily. The bleeding pattern was registered in diary cards. Endometrial status was assessed by vaginal ultrasound and endometrial biopsy. Lipid levels were measured by ELISA. MAIN OUTCOME MEASURE(S): The number of patients who dropped out of the study and the number of days each patient reported spotting or bleeding were recorded. Endometrial thickness was measured and histologic examination of the endometrial tissue was performed. Plasma levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were measured. RESULT(S): Fourteen women dropped out of the intermittent dosing group and 13 dropped out of the continuous dosing group. Irregular spotting or bleeding occurred at a similar rate in both groups. Biopsies performed at the end of the study showed adequate endometrial stabilization in both groups. No significant changes in lipid levels were detected with either regimen. CONCLUSION(S): Both regimens were similarly effective. The high rate of atrophic endometria suggests the possibility of further reduction of the progestin dose.

Administration, Cutaneous↗
PubMed1999

Effect of menopause and different combined estradiol-progestin regimens on basal and growth hormone-releasing hormone-stimulated serum growth hormone, insulin-like growth factor-1, insulin-like growth factor binding protein (IGFBP)-1, and IGFBP-3 levels.

OBJECTIVE: To determine the effects of menopause and three different formulations of E2 plus medroxyprogesterone acetate on serum concentrations of basal and growth hormone-releasing hormone (GHRH)-stimulated growth hormone (GH), insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein (IGFBP)-1, IGFBP-3, insulin, and C peptide. DESIGN: Prospective, controlled trial. SETTING: Menopausal outpatient clinic at an academic tertiary care hospital. PATIENT(S): Nineteen postmenopausal women with different menopausal ages. Seventeen premenopausal women were included as controls. INTERVENTION(S): Oral estrogen (E2 valerate, 2 mg/d) or transdermal estrogen (50-microg or 100-microg E2 patch) was administered for 8 weeks. Medroxyprogesterone acetate (5 mg/d) was administered during weeks 3, 4, 7, and 8 of each protocol. Blood samples were collected before treatment and after the completion of each protocol from postmenopausal women, and on cycle days 6-8 from premenopausal women. MAIN OUTCOME MEASURE(S): Levels of GH, IGF-1, IGFBP-1, IGFBP-3, insulin, and C peptide. RESULT(S): Basal GH levels were negatively correlated with age in premenopausal women but not in postmenopausal women. The area under the GHRH-induced GH curve decreased in older postmenopausal women after the oral estrogen protocol. Levels of IGF-1 diminished after the oral E2 protocol in postmenopausal women. CONCLUSION(S): The administration of oral, but not transdermal, E2 plus medroxyprogesterone acetate at the usual clinical doses used in postmenopausal women decreased IGF-1 levels and the response of GH to GHRH in older women. No substantial changes were detected in IGFBP-1, IGFBP-3, insulin, or C peptide levels.

Adult↗
PubMed1999

Do human concepti have the potential to enter into diapause?

Although there is no direct evidence as to whether human concepti have the potential to enter into diapause before implantation, the possibility that human concepti may be capable of following this developmental pathway if exposed to an appropriate environment cannot be ruled out. Direct evidence remains elusive because of the ethical restraints associated with research activities within this area of knowledge. If conceptus diapause has evolved in primates and persists at the present time despite its apparent limited or no adaptive advantage, artificial induction of diapause in humans may have clinical implications for increasing: (i) the viability of concepti after biopsy, freezing-thawing or any other experimental procedure that tends to decrease cell numbers or division rate of concepti; and (ii) the relatively low implantation rates obtained at the present time after uterine transfer of human concepti fertilized in vitro. Furthermore, conceptus diapause may be a good paradigm to understand the interplay between the different genetic/molecular components of both the conceptus and endometrium at implantation.

Adaptation, Physiological↗
PubMed1999

Long-term effects of postovulatory aging of mouse oocytes on offspring: a two-generational study.

Aims of this study were to analyze the long-term effects of postovulatory aging of mouse oocytes on 1) reproductive traits of parental (F(0)) and first (F(1))-generation females (pregnancy rate, gestation length, litter size, perinatal death, and sex ratio of offspring) and 2) developmental and behavioral variables of F(1) and second-generation (F(2)) offspring (birth weight and weight gain during preweaning development, postnatal day of attainment of immediate righting, spontaneous motor activity, and passive and active conditioned learning ability). Hybrid (C57BL/6JIco x CBA/JIco) females were artificially inseminated at 13 h (control group) or 22 h (oocyte-aged group) after GnRH injection. Experimental (oocyte-aged group) F(0) females exhibited lower pregnancy rate, shortened gestation length, decreased litter size, higher perinatal death of their pups, and increased percentage of male offspring compared to control F(0) females. Postovulatory aging of oocytes was also associated with increased number of growth-retarded pups, delayed development of the righting reflex, and higher spontaneous motor activity and emotionality of F(1) offspring. Postovulatory aging of F(0) oocytes did not affect birth weight, weight gain during preweaning development, passive and active conditioned learning ability of F(1) offspring, or reproductive traits of F(1) females or developmental and behavior variables of F(2) offspring.

Animals↗
PubMed1998

The heparin-glutathione test: an alternative to the hypo-osmotic swelling test to select viable sperm for intracytoplasmic sperm injection.

OBJECTIVE: To evaluate the heparin-glutathione test (HEGLUT) for the selection of viable sperm for intracytoplasmic sperm injection (ICSI). DESIGN: A prospective study. SETTING: Department of Pediatrics, Obstetrics and Gynecology, University of Valencia and Instituto Valenciano de Infertilidad. PATIENT(S): Semen samples from healthy donors and patients with infertility. INTERVENTION(S): Sperm samples were kept in culture for different periods in Ham's F-10 medium supplemented or not supplemented with heparin, reduced glutathione (GSH), or a heparin-GSH mixture. Control and heparin-GSH-treated spermatozoa were injected into hamster oocytes. The HEGLUT and ICSI were performed. MAIN OUTCOME MEASURE(S): Sperm nuclear decondensation, progressive and nonprogressive motility, and male pronucleus formation. RESULT(S): The maximum proportion of sperm nuclear decondensation (28.7%+/-2.1% versus 2.6%+/-0.5% in the control group) was reached after 60 minutes of incubation in the presence of a heparin-GSH mixture. Differences in the percentages of progressive and nonprogressive motility among treatments and times of incubation, although statistically significant, were biologically negligible. No statistically significant differences were observed in the rate of sperm head decondensation (8.2% [4/49] versus 11.1% [6/54]) and male pronucleus formation (18.4% [9/49] versus 22.2% [12/541) after the injection of control and treated spermatozoa into hamster oocytes. CONCLUSION(S): The HEGLUT may offer an alternative to the hypo-osmotic swelling test for the selection of viable sperm for ICSI.

Animals↗
PubMed1998

Dithiothreitol prevents age-associated decrease in oocyte/conceptus viability in vitro.

The present study was designed to ascertain whether the negative effects on reproductive potential of post-ovulatory ageing in vitro of oocytes can be prevented by antioxidant therapy. Mouse metaphase II (MII) oocytes were aged in vitro for 12 h prior to insemination in the presence of varying concentrations of L-ascorbic acid, 6-methoxy-2,5,7,8-tetramethylchromane-2-carboxylic acid (Trolox), L-cystine dihydrochloride, ethylenediaminetetraacetic acid (EDTA), beta-mercaptoethanol and DL-dithiothreitol (DTT). In-vitro ageing of oocytes was associated with lower fertilization rate, higher proportion of concepti exhibiting cellular fragmentation at 24 h post-insemination and lower percentage of concepti reaching the blastocyst stage. Ascorbic acid, Trolox and EDTA had no effect on cellular fragmentation or potential of oocytes for development. However, the probability of an oocyte reaching the blastocyst stage was decreased (P < or = or = 0.05) in oocytes incubated in the presence of L-cystine (50 and 500 microM) and beta-mercaptoethanol (5, 50 and 500 microM) when compared to control aged oocytes. Age-associated cellular fragmentation at 24 h post-insemination was partially prevented (P < or = 0.05) by incubating oocytes in the presence of beta-mercaptoethanol (500 microM). DTT (50 and 500 microM) increased (P < or = 0.05) fertilization rate and number of cells at 81 h post-insemination to levels similar to those exhibited by control oocytes. Furthermore, both age-associated fragmentation at 24 h post-insemination (P < or = 0.05) and decreased potential of oocytes for development to the blastocyst stage (P < or = 0.05) were prevented, at least in part, by culturing oocytes in the presence of DTT (50 microM). Although the mechanism by which DTT exerts its beneficial effects on aged oocytes remains to be elucidated, it may protect oocytes by preventing oxidation of free thiol groups and/or altering a redox-independent signalling pathway that mediates cellular fragmentation and death.

Animals↗
PubMed1998

Two distinct two-step ranks of progesterone stimulation after three different levels of oestrogen priming. Effect on induction of luteinizing hormone surges in young and climacteric women.

Age and menopausal status were evaluated as potential modulators of the progesterone action in the initiation of the mid-cycle luteinizing hormone (LH) surge in women. Three distinct levels of oestradiol priming were used, in combination with two different two-step ranks of progesterone stimulation (10/25 mg and 25/50 mg i.m. injections of progesterone in oil, over 2 consecutive days) in two groups of women, ten premenopausals, aged between 18 and 25 years, and 14 postmenopausals, aged between 48 and 57 years. The low, moderate and high levels of oestradiol priming were defined in the premenopausal group by days 5 and 9 of the cycle, and 0.4 mg transdermal oestradiol applied in the early follicular phase respectively. The corresponding situation in the postmenopausal women was defined by the absence of treatment, 0.1 mg transdermal oestradiol, and 0.4 mg transdermal oestradiol respectively. The oestradiol patches were maintained for 5 days, and the first progesterone dose administered on day 3 of treatment. Unambiguous LH surges, detected in serum and urine, were restricted to the protocols using 0.4 mg oestradiol in both groups, with an onset soon after progesterone administration. The surge was higher in the postmenopausal group in serum and urine. The percentage LH increase above baseline, however, was higher in the premenopausal women. The dose of progesterone did not result in any changes in pituitary LH release. Therefore, the oestradiol threshold for the progesterone stimulatory effect on LH release was similar in both groups. The postmenopausal women did not yield defective LH surges when adequately primed with oestradiol and progesterone.

Adult↗
PubMed1998

Long-term effects of delayed parenthood.

The present study aims to define, characterize and compare the long-term effects on offspring of delayed parenthood. Data published so far on this topic show that maternal and paternal ageing may affect offspring by different mechanisms. Delayed motherhood is characterized by increased probability of obstetric complications and/or fetal and perinatal problems which, in turn, may increase the risks of mortality and morbidity in newborns and later life. Furthermore, maternal ageing is distinguished by a decreased ratio of male to female infants and higher odds of conceiving a trisomic child and/or an individual suffering from mitochondrial DNA disorders. In contrast, delayed fatherhood is associated with higher risks of conceiving an individual suffering from new inheritable-mutation disorders. The different pattern of disease in offspring associated with maternal and paternal ageing may be explained, among other factors, by the fact that (i) oocytes of middle-aged women may suffer oxidative stress because their mitochondria produce higher amounts of reactive oxygen species; (ii) diplotene oocytes and to a lesser extent metaphase I and II oocytes have an efficient DNA repair system which is essentially independent of maternal age; and (iii) mitochondria are transmitted to the next generation along the matrilineal line. Moreover, (i) the activities of antioxidant enzymes within the seminal plasma and spermatozoa from older men may be reduced and so spermatozoa may be more vulnerable to mutational changes than spermatozoa from younger men; and (ii) late spermatids, and immature and mature spermatozoa do not have a DNA repair system.

DNA Repair↗