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Seasonality in twin and triplet births.

A study has been made of the twin births in England and Wales 1952-59 and 1963-75. There is good evidence that the incidence of opposite-sexed (and by inference, dizygotic) twin births is seasonal, being about 5% higher in December than June. Triplet births seen to show a seasonal variation at about the same location and with double the amplitude. It seems likely that this seasonal variation of polyzygotic maternities is due to seasonal variation in the rates of multiple ovulation rather than to seasonal variation in any of the other reproductive parameters which could, in principle, be responsible (coital rate, spontaneous abortion, probability of fertilization). It is possible that such an hypothesized variation is due to seasonal variation in food consumption. Evidence in regard to seasonal variance in monozygotic twinning rates is equivocal but a number of considerations suggest that they too are subject to seasonal variation. If this is so, the peak incidence of MZ twin births occurs around November.

Abortion, Spontaneous↗

Dibromoacetic acid, a commonly occurring water disinfection by-product, does not affect follicular populations in neonatal rats.

To investigate whether the mechanism of dibromoacetic acid (DBA) toxicity involves disruption of primordial germ cell migration and/or follicular formation, pregnant and lactating female Sprague-Dawley rats were gavaged daily with 0, 1, 5, or 50 mg DBA/kg body weight beginning on gestation day 17 and continuing through postnatal day 7. Reproductive parameters in 4 groups (n = 10 per group) of female neonatal rats exposed to DBA were examined. Maternal weight, litter size, and gender ratio did not differ across treatment groups, and major organ weights (spleen, liver, kidneys, uterus, and ovary) did not differ from control. Ovaries were serially sectioned at 8 microm and every eighth section was used for morphometry. All healthy follicles within a section were categorized into one of five types and the area of section was measured. Follicular populations at all stages of development did not differ among treatment groups. Thus, exposure to DBA during the period of follicular formation did not affect follicular populations in neonatal rats. These data suggest that rodents may not be a useful model for DBA toxicity assessment. Further research into species differences in the mechanism and timing of DBA toxicity is warranted.

Acetates↗

Estrogen-metabolizing gene polymorphisms and age at natural menopause in Caucasian women.

BACKGROUND: Lifestyle parameters, personal history and genetic factors are thought to affect the timing of natural menopause in humans. Based on their biological function, estrogen-metabolizing gene polymorphisms have been regarded as candidate genes for early menopause. METHODS: In the present cross-sectional, multi-centre study, we analysed nine single nucleotide polymorphisms of six estrogen-metabolizing genes [three estrogen-synthesizing genes, i.e. 17-beta-hydroxysteroid dehydrogenase type 1 (17-beta HSD), cytochrome P-450 (CYP) 17 and CYP19; and three estrogen-inactivating genes, i.e. catechol-O-methyltransferase (COMT), CYP1A1 and CYP1B1] by sequencing-on-chip-technology in 1360 Caucasian women with natural menopause. Women's lifestyle parameters, reproductive and personal histories were ascertained. RESULTS: Carriage of at least one mutant allele of the CYP1B1-4 Asn453Ser A--> G polymorphism (P = 0.004) and the number of full-term pregnancies (P < 0.001) were found to be independently associated with age at natural menopause. Women with at least one polymorphic allele of CYP1B1-4 experienced natural menopause earlier than non-carriers of the polymorphism [mean (SD) 48.6 (5.0) versus 49.4 (4.3) years]. Women with no, one, two and three or more full-term pregnancies experienced natural menopause at 48.5 (5.0), 48.8 (4.8), 49.5 (4.2) and 49.6 (4.6) years, respectively. CONCLUSION: We present the most comprehensive data on estrogen-metabolizing gene polymorphisms and timing of natural menopause to date. The number of full-term pregnancies and the CYP1B1-4 polymorphism are significant predictors of timing of natural menopause in Caucasian women.

Adult↗

Metformin treatment of polycystic ovary syndrome improves health-related quality-of-life, emotional distress and sexuality.

BACKGROUND: In polycystic ovary syndrome (PCOS), changes in physical appearance, menstrual disturbances and infertility result in psychological distress and reduced quality-of-life. Metformin improves biochemical, clinical and reproductive parameters in PCOS women. In a prospective, observational study, we analysed the effects of metformin treatment on health-related quality-of-life (HRQL), emotional well-being and sexuality in PCOS. No placebo-treated control group was included. METHODS: Before, during and after 6 months of treatment, changes in clinical and endocrine parameters, quality-of-life, psychological disturbances and sexuality were assessed in 64 PCOS patients using validated questionnaires (SF-36, SCL-90-R) and visual analogue scales. Patients were also compared with published normative data for the validated questionnaires. RESULTS: During treatment, HRQL, particularly the psychosocial aspects (indicated by significant increases in SF-36 scales Vitality, Social Function, Emotional Role Function, Mental Health, Psychological Sum scale) and emotional well-being (reflected by significant lowering of SCL-90-R scales) improved. These improvements in HRQL were significantly correlated with a reduction in body weight and significantly more pronounced in patients with normalized menstrual cycles. In addition, PCOS women were significantly more satisfied with their sex life and reported higher frequencies of sexual intercourse following treatment. CONCLUSION: Treatment can improve the psychosocial, emotional and psychosexual situation of PCOS patients. Although at least some of these effects may be related to the reduction of individual clinical symptoms (i.e. weight loss, normalization of menstrual disturbances, improvement of acne), this observational study does not allow us to clearly discern the role of symptom constellation and does not preclude non-specific and/or placebo effects. Nevertheless, emotional distress and reduced quality-of-life are clearly not an inevitable consequence of PCOS and should be considered as adjunct treatment goals in future studies.

Adult↗

Effect of selection for growth on onset of sexual maturity in randombred and growth-selected lines of Japanese quail.

An experiment was conducted to determine the effect of selection for growth (BW) on the onset of reproduction (first egg) in Japanese quail hens from growth-selected (HW) and randombred (R1) lines. The HW line had undergone over 40 generations of selection for increased 4-wk BW and was originally developed from the R1 line. Data were collected over two consecutive hatches and summarized by hatch and within lines. Body weight at 35 d of age was positively correlated with BW at sexual maturity (first egg) in both the R1 and HW lines, but these correlations were not significant in both hatches for either line (Hatch 1-R1; Hatch 2-HW; P < or = 0.05). There was a negative correlation between age at sexual maturity (days to first egg) and 35 d BW in both lines with the exception of the HW hens in Hatch 2. Age at sexual maturity and BW at sexual maturity was positively correlated (P < or = 0.001) in the R1 line but did not show the same relationship in the HW line. Age at sexual maturity and weight of the abdominal fat pad were positively correlated in the R1 line (Hatch 1, P < or = 0.01; Hatch 2, P < or = 0.001), but this relationship was not significant in the HW line. Age at sexual maturity and follicle number was negatively correlated in both lines but was not significant in Hatch 2 of the HW line. Follicle size, however, was positively correlated with days to first egg in only Hatch 2 (P < or = 0.001) of the HW line. The data suggest that the relationships between the onset of sexual maturity and both reproductive parameters and carcass traits in hens from consecutive hatches of HW quail are less clear than in the R1 line.

Aging↗

Bromochloroacetic acid exerts qualitative effects on rat sperm: implications for a novel biomarker.

Disubstituted haloacid by-products of drinking water disinfection such as dibromoacetic acid and dichloroacetic acid have been shown to perturb spermatogenesis and fertility in adult male rats. In the present study we sought to establish whether equimolar exposure to bromochloroacetic acid (BCA), a prevalent by-product in finished drinking water, is also capable of disrupting these endpoints, and if so to determine whether the novel biomarker of fertility (SP22) would be correlated with subfertility induced by testicular toxicity. A dose range finding study indicated that body weight was not affected by exposure to 14 daily doses of 72 mg/kg BCA while numerous male reproductive parameters were altered, including decreases in the number and progressive motility of cauda epididymal sperm. In addition, there was an increased incidence of delayed spermiation in the testes of males exposed to 72 mg/kg BCA. In the definitive study, exposures ranged from 8 to 72 mg/kg, the fertility of cauda epididymal sperm was evaluated by in utero insemination, and the two-dimensional profile of cauda sperm membrane proteins was evaluated quantitatively. The morphology of both caput and cauda epididymal sperm was altered by 72 mg/kg BCA. The fertility of cauda epididymal sperm, the percentages of progressively motile sperm and progressive tracks, and two sperm membrane proteins (SP22 and SP9) were decreased significantly by each BCA exposure. While the two sperm proteins and the two measures of progressive motility were each significantly correlated with fertility, only one of these measures (i.e., SP22) had an r value of greater than 0.5. When data for SP22 and fertility were fit to a nonlinear model, r(2) was 0.84. Using this exposure paradigm, the no-observed-effect level for BCA is less than 8 mg/kg. Moreover, SP22 may be useful in predicting compromised fertility after exposure to by-products of drinking water disinfection.

Acetates↗

Evaluation of a 15-day screening assay using intact male rats for identifying antiandrogens.

An in vivo screening assay using intact adult male rats has been evaluated for its ability to detect six antiandrogenic compounds via oral administration. The test compounds included cyproterone acetate (CPA), flutamide (FLUT), p,p'-DDE (DDE), di-n-butyl phthalate (DBP), linuron (LIN), and vinclozolin (VCZ). Two of the test compounds (DDE and FLUT) have been previously evaluated in the 15-day intact male assay with compound administration via intraperitoneal injection (ip). For the current studies, male rats were dosed for 15 days via oral gavage and euthanized on the morning of test day 15. The endpoints evaluated included final body and organ weights (liver, thyroid gland, testes, epididymides, prostate, seminal vesicles with fluid, accessory sex gland unit [ASG]), serum hormone concentrations (testosterone [T], estradiol [E2], dihydrotestosterone [DHT], luteinizing hormone [LH], follicle stimulating hormone [FSH], prolactin [PRL], T(3), T(4), and thyroid stimulating hormone[TSH]), and histopathology of the testis, epididymis, and thyroid gland; positive results for each endpoint are described below. In addition, an evaluation of immune system endpoints (humoral immune function, spleen and thymus weights, and spleen cell number) was conducted on a subset of animals dosed with either DDE or FLUT. All six endocrine-active compounds (EACs) increased relative liver weight. FLUT and VCZ caused the typical pattern for an androgen receptor (AR) antagonist, although not all endpoints were statistically significant for VCZ: decreased ASG weights, hormonal alterations (increased T, DHT, LH, and FSH), and induced Leydig cell hypertrophy and/or hyperplasia. CPA caused effects consistent with its mixed AR antagonist/progesterone receptor agonist activity: it decreased ASG weights, caused hormonal alterations (increased T and E2; decreased FSH), and caused spermatid retention. DBP, a compound with antiandrogen-like activity via a nonreceptor mediated mechanism, caused hormonal alterations (decreased T, DHT, and E2; increased LH, FSH, and PRL) and induced general testicular degeneration. LIN, a weak AR antagonist, decreased ASG weights, caused hormonal alterations (decreased T, DHT, and LH; increased E2), and caused spermatid retention. Unlike the other AR antagonists evaluated, DDE, a weak AR antagonist, did not alter reproductive parameters. All six antiandrogens caused some effects on thyroid parameters, although only CPA, DDE, and VCZ caused results consistent with a potential thyroid-modulator. FLUT and DDE did not alter the primary humoral immune response to SRBC, spleen or thymus weights, or spleen cell number. In the current study, 5 of the six test substances were identified as endocrine-active substances consistent with their known/proposed mechanism(s) of action. The effects that were observed in the current study via oral (gavage) compound administration were similar to the responses that were observed by the ip route in previous studies for DDE and FLUT. This report, in addition to the > 20 compounds that have already been examined using the 15-day intact male assay, supports this assay as a viable screening assay for detecting EACs, and also illustrates that the ability to identify EACs using the intact male assay will be equivalent regardless of the route of compound administration.

Androgen Antagonists↗

Age-related and seasonal variation in the Sertoli cell population, daily sperm production and serum concentrations of follicle-stimulating hormone, luteinizing hormone and testosterone in stallions.

Testes and blood samples were obtained from 201 stallions aged 6 months to 20 years in either December-January (nonbreeding season) or June-July (breeding season) to study the effect of age and season on reproductive parameters. Seasonal differences in the Sertoli cell population of adult (4-20 years old) horses were characterized by a 36% larger number of Sertoli cells in the breeding season than in the nonbreeding season. Seasonal elevation in the Sertoli cell population was associated with an increase in testicular weight and daily sperm production per testis (DSP/testis). Concentrations of luteinizing hormone (LH) and testosterone in serum varied with season. Although follicle-stimulating hormone (FSH) concentrations also tended to be higher in the breeding season, this trend was not statistically significant (P less than 0.08). Sertoli cell numbers averaged over both seasons, like testicular weights, increased with age until 4-5 years of age, but were stabilized thereafter. This age-related difference was also associated with increased concentrations of FSH, LH and testosterone, and with increased DSP/testis. The Sertoli cell population was capable of increasing in the adult horse by fluctuating its size with season. The number of elongated spermatids per Sertoli cell over both seasons increased with age up to 4-5 years of age and was stabilized thereafter. Thus, seasonal and/or age-related differences in DSP/testis were associated with significant elevations in serum concentrations of FSH, LH and testosterone, testicular weights, numbers of elongated spermatids per Sertoli cell and elevation of the Sertoli cell population.

Age Factors↗

Density-dependent growth as a key mechanism in the regulation of fish populations: evidence from among-population comparisons.

It is generally assumed that fish populations are regulated primarily in the juvenile (pre-recruit) phase of the life cycle, although density dependence in growth and reproductive parameters within the recruited phase has been widely reported. Here we present evidence to suggest that density-dependent growth in the recruited phase is a key process in the regulation of many fish populations. We analyse 16 fish populations with long-term records of size-at-age and biomass data, and detect significant density-dependent growth in nine. Among-population comparisons show a close, inverse relationship between the estimated decline in asymptotic length per unit biomass density, and the long-term average biomass density of populations. A simple population model demonstrates that regulation by density-dependent growth alone is sufficient to generate the observed relationship. Density-dependent growth should be accounted for in fisheries' assessments, and the empirical relationship established here can provide indicative estimates of the density-dependent growth parameter where population-specific data are lacking.

Aging↗

The Physiological Basis for Cytokinin Induced Increases in Pod Set in IX93-100 Soybeans.

Previous investigations have shown the feasibility of increasing pod number on legumes by the application of 6-benzylaminopurine (BA) directly to the raceme. These investigations were designed to determine what reproductive parameter was affected by cytokinin application, and if these applications were overcoming a deficiency in root-produced cytokinins during late flowering. Five individual main stem racemes on greenhouse grown soybeans (Glycine max L. Merr.) were treated with 2 millimolar BA. A single application of BA when pods appeared at 25 to 50% of the proximal floral positions resulted in a 58% increase in pod set due primarily to a 33% reduction in floral abscission. Applications of BA at later intervals also resulted in significant reductions in total abscission. When three applications of BA were imposed on the upper five nodes of field grown soybeans, total pod number and seed weight were significantly increased in this section of the canopy by 27 and 18%, respectively. Throughout the flowering period, root pressure exudate was sampled for the subsequent separation and quantification of zeatin, dihydrozeatin, zeatin riboside, dihydrozeatin riboside, and isopentenyladenine. Total cytokinin flux peaked from 0 to 9 days after flowering began, and then dropped to one-half of this level by 15 days postanthesis. The probability that a flower would initiate a pod was directly related to the concentration of total cytokinins present in the exudate when the flower opened.

Journal Article↗

Congenital defects among the offspring of epileptic fathers: role of the genotype and phenytoin therapy in a mouse model.

The progeny of coisogenic C57BL/6J mice homozygous for either the tottering (tg/tg) or wildtype (+/+) allele were examined to determine the role of parental seizure disorders and paternal anticonvulsant drug therapy on the incidence of congenital malformations. Pregnancy outcomes in which one, both, or neither of the parents had an epileptic genotype were compared for various maternal and fetal reproductive parameters. In addition, the progeny from phenytoin-treated male tottering (tg/tg) mice with a spontaneous seizure disorder and from control untreated (+/+) male mice were similarly examined for evidence of congenital defects. The results of these experiments suggest that neither the parental genotype with respect to seizure disorders nor paternal anticonvulsant treatment with phenytoin is responsible for an increased incidence of congenital malformations.

Abnormalities, Drug-Induced↗

Influence of ethanol on reproductive functions of the adult male rat as a function of body weight.

Adult male rats were exposed to alcohol vapors for 3-4 weeks. Blood alcohol levels (BAL) ranged from 90 to 190 mg/100 ml. BAL of greater than or equal to 0-130 mg/100 ml were compatible with adequate body weight gains and were not associated with diminished plasma testosterone (T) levels or reduced sex organ weights. BAL greater than or equal to 180 mg/100 ml were associated with inhibition of androgen secretion only in those animals who failed to grow. From these results we conclude that in growing animals, the medium term exposure to ETOH leads to inhibition of reproductive parameters when high BALs induce weight loss, but not when adequate body growth is maintained.

Animals↗

Alcohol stimulates ACTH secretion in the rat: mechanisms of action and interactions with other stimuli.

This review discusses some of the mechanisms through which alcohol (EtOH) alters the activity of the hypothalamic-pituitary-adrenal (HPA) axis. In adult rats, acute EtOH treatment increases plasma ACTH and corticosteroids levels primarily by stimulating the release of corticotropin-releasing factor (CRF) and possibly vasopressin (VP) from nerve terminals in the median eminence. Increased CRF gene transcription in the hypothalamus may also be important. The HPA axis remains activated during chronic EtOH exposure, although habituation may take place. Changes in the responsiveness of hypothalamic neurons, a phenomenon itself dependent in part on a number of intermediate secretagogues, as well as decreased pituitary responsiveness to VP, all play a role. Finally, the activity of the HPA axis is influenced by exposure to EtOH during embryonic development, with mature offspring showing hyporesponsiveness to many stimuli. These altered responses appear to be caused in part by changes in the synthesis/release CRF, possibly under the influence of nitric oxide. CRF, VP, ACTH, and corticosteroids are important regulators of the immune system, behavior, metabolic pathways, and reproductive parameters. Alcohol therefore may influence such functions through the pathological secretion of these hormones. A better understanding of the mechanisms through which the drug alters their release thus may permit the development of therapies designed to alleviate some of the consequences of alcoholism.

Adrenocorticotropic Hormone↗

Effects of olfactory bulbectomy, melatonin, and/or pinealectomy on three sublines of the Dunning R3327 rat prostatic adenocarcinoma.

Conventional antiandrogen therapy for prostatic cancer generally results in the death of androgen-dependent cells, resulting in shrinkage of the tumor, followed by regrowth of the tumor as androgen-insensitive cells take over. Because of reported antigonadotropic and antineoplastic effects of the pineal hormone melatonin (MEL), we hypothesized that this indole might provide an effective therapy for prostate cancer, as it would be effective against both populations of tumor cells. We used three sublines of the Dunning R3327 rat prostatic adenocarcinoma to determine whether MEL could suppress the growth of these tumors and, if so, by what mechanisms this occurs. In one experiments, we compared the growth of a well-differentiated slow-growing Dunning tumor in rats given MEL combined with the potentiating procedure olfactory bulbectomy (BULBX), with that in rats pinealectomized (PINX) or untreated. Tumor growth in BULBX-MEL rats was significantly suppressed over that in the other two groups, as were the weights of the gonads and accessory sex glands. Tumor morphology, DNA concentration, and androgen receptor concentration and distribution were identical in untreated controls and in BULBX-MEL rats, suggesting that the treatment affected all populations of tumor cells equally. With another strain of well-differentiated slow-growing Dunning tumor, we examined the effects of MEL in rats with and without BULBX. Reproductive parameters were not suppressed in BULBX-MEL rats and, while there was a trend toward slower tumor growth in this group, this was not significant. Intact rats given MEL grew larger tumors than did control rats but, again, differences were not significant. In a third experiment, we examined a fast-growing androgen-insensitive anaplastic Dunning tumor. PINX was without effect on this tumor, but BULBX-MEL resulted in a significant suppression of one of the constants in the logistic equation fitted to the growth curves. This indicates that there were some direct antitumor effects of BULBX-MEL on this tumor strain. We conclude that MEL suppresses growth of some Dunning tumor strains.

Adenocarcinoma↗

Metronidazole for the treatment of bovine pyometra.

Metronidazole, an antibiotic with specific activity against anaerobic bacteria, was assessed as a treatment for bovine pyometra. A preliminary experiment with metronidazole-neomycin was followed by an experiment in which metronidazole-ampicillin was compared with povidone iodine. Each treatment was given as a single intrauterine infusion. The success of therapy was judged by clinical examination, bacteriological examination before and after treatment and, in the second experiment, by post treatment reproductive performance. Before treatment 45 of the 84 cows in both experiments were infected with a mixture of anaerobic and aerobic bacteria, 23 cows were infected with aerobes alone and significant bacteria were not isolated from 16 cows. Complete bacteriological and clinical cures were achieved in 23 of 32 cows treated with metronidazole-neomycin, 15 of 32 cows treated with metronidazole-ampicillin and 1 of 20 cows treated with iodine. When only those cows with mixed anaerobe/aerobe infections were considered, complete cures occurred in 12 of 17 cows treated with metronidazole-neomycin, and 11 of 16 cows treated with metronidazole-ampicillin, but none of the 12 cows treated with iodine. Twenty-two of 29 cows treated with metronidazole-ampicillin conceived after treatment (mean 51.4 days), while 9 of 18 cows treated with iodine conceived (mean 58.7 days). Statistically, metronidazole-ampicillin treatment produced significantly better clinical and bacteriological cure rates than iodine treatment (P less than 0.05), but the differences in reproductive parameters were not significant.

Ampicillin↗

A mathematical model of CO2 effect on cardiovascular regulation.

The effect of changes in arterial CO2 tension on the cardiovascular system is analyzed by means of a mathematical model. The model is an extension of a previous one that already incorporated the main reflex and local mechanisms triggered by O2 changes. The new aspects covered by the model are the O2-CO2 interaction at the peripheral chemoreceptors, the effect of local CO2 changes on peripheral resistances, the direct central neural system (CNS) response to CO2, and the control of central chemoreceptors on ventilation and tidal volume. A statistical comparison between model simulation results and various experimental data has been performed. This comparison suggests that the model is able to simulate the acute cardiovascular response to changes in blood gas content in a variety of conditions (normoxic hypercapnia, hypercapnia during artificial ventilation, hypocapnic hypoxia, and hypercapnic hypoxia). The model ascribes the observed responses to the complex superimposition of many mechanisms simultaneously working (baroreflex, peripheral chemoreflex, CNS response, lung-stretch receptors, local gas tension effect), which may be differently activated depending on the specific stimulus under study. However, although some experiments can be reproduced using a single basal set of parameters, reproduction of other experiments requires a different combination of the mechanism strengths (particularly, a different strength of the local CO2 mechanism on peripheral resistances and of the CNS response to CO2). Starting from these results, some assumptions to explain the striking differences reported in the literature are presented. The model may represent a valid support for the interpretation of physiological data on acute cardiovascular regulation and may favor the synthesis of contradictory results into a single theoretical setting.

Animals↗

Effect of spinal cord transection on the reproductive system in the female rat.

Cycling rats had their spinal cord transected (SCT) at the T5 vertebral level and/or were unilaterally ovariectomized (ULO) at metestrus, and allowed to cycle either for one estrous cycle or for 19 days. Estrous cycle lengths were increased following SCT in all animals. After one cycle, SCT rats showed no effect on other reproductive parameters studies. In contrast, after 19 days decreases in body and ovarian weights, and number of follicles greater than 448 micrometers and ova shed per ovary were observed. When ULO was performed in conjunction with SCT, compensatory ovarian responses occurred. The data demonstrate that an intact adrenergic system is necessary for normal ovarian function in the intact rat but not necessary for compensatory ovarian responses to occur following ULO.

Animals↗

Growth and development in the rat during sub-chronic exposure to low levels of hydrogen sulfide.

The effects of low levels of hydrogen sulfide (H2S) on mammalian growth and development are unknown although it has long been postulated that H2S can inhibit critical developmental functions through the cleavage of disulfide bonds and chelation of essential metal ions. Gravid rat dams exposed to H2S (less than or equal to 75 PPM) from day 6 of gestation until day 21 postpartum (PP) demonstrated normal reproductive parameters until parturition. At parturition, however, delivery time was extended in a dose dependent manner with a maximum increase of 42% at 75 PPM. Maternal liver cholesterol content was elevated significantly on day 21 postpartum following exposure to 75 PPM H2S each day for 6 weeks. Pups which were exposed in utero and neonatally to day 21 postpartum developed with a subtle decrease in time of ear detachment and hair development and with no other observed change in growth and development through day 21 postpartum.

Animals↗