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Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 18). Comparative 4 and 2 weeks oral repeated dosing studies on male reproductive organs in rats treated with 5-fluorouracil.

Oral repeated toxicity studies were conducted to compare the effects of 5-fluorouracil (5-FU) administered for 4 or 2 weeks on male reproductive organs of Sprague-Dawley (SD) rats. In both studies, decrease of feces, abnormal fur and emaciation were observed. On gross autopsy examination, softening/atrophy of the testis as well as atrophy of accessory reproductive organs were noted, and absolute organ weights of male reproductive organs were almost all reduced in both studies. Histopathologically, degeneration of the seminiferous epithelium in the testis and desquamated cell debris in the epididymal ducts were apparent after both time periods. In the 2-week study, furthermore, exfoliation of the seminiferous epithelium, formation of multinucleated giant cells and vacuolation of Sertoli cells in the seminiferous tubules in the testis, and decrease of sperms in the epididymal ducts were observed. The present results indicated that a 2-week study is sufficient to detect effects on the male reproductive organs of 5-FU treatment. In our study, however, changes in associated parameters after 2-week treatment of 8-week-old rats were greater than those after 4 weeks in 6-week-old rats. Thus, for detection of 5-FU-induced male reproductive toxicity, we can evaluate more accurately by using maturated rats of the same age.

Animals↗

An assessment of dietary folic acid levels during gestation and lactation on reproductive and lactational performance of sows: a cooperative study. S-145 Committee on Nutritional Systems for Swine to Increase Reproductive Efficiency.

Crossbred female swine (n = 393) were used in a multiparity study at five experiment stations to evaluate the effects of dietary supplementation of folic acid (FA) on serum folates status and reproductive performance. The dietary treatments were a corn-soybean meal basal diet (calculated FA, .34 ppm) supplemented with 0, 1, 2, or 4 ppm FA. Experimental diets were fed continuously from a minimum of 21 d before first mating throughout the entire study. At one station, blood samples for radioimmunoassay determination of serum folates concentration were collected by vena cava puncture at mating, d 55 of gestation, d 110 of gestation, and at weaning. Stage of reproduction and dietary FA supplementation affected (P < .005) serum folates concentrations. Serum folates declined from mating to d 55, remained low at d 110, and returned to higher levels at weaning. Linear increases (P < .001) in serum folates with increasing level of dietary FA were observed at each reproductive stage. Over the course of the study, reproductive performance criteria including total pigs born, live pigs at birth and d 21, and individual pig and litter weight at birth and d 21 were not affected (P > .10) by inclusion of FA in the diet. The number of days postweaning to estrus also was not affected by FA treatment. Under the conditions of this experiment, increasing level of FA in the diet had a pronounced effect in attenuating decreased serum folates concentration during gestation but was without benefit to reproductive performance.

Animal Feed↗

The cost of realized sexual reproduction: assessing patterns of reproductive allocation and sporophyte abortion in a desert moss.

The desert moss Syntrichia caninervis exhibits one of the most skewed sex ratios in the plant kingdom, with female individuals far outnumbering male individuals (exceeding 14♀:1♂). The "cost of sex hypothesis" derives from allocational theory and predicts that the sex which is most expensive should be the rarer sex. This hypothesis, which, as considered here represents the realized cost of sexual reproduction, is contingent upon two assumptions that are explored: (1) that male sex expression is more expensive than female sex expression, and (2) that sexual reproduction is resource limited. Using inflorescence biomass and discounting sperm, male sex expression was found to be in the neighborhood of one order of magnitude more expensive than female sex expression, and this difference is reflected in higher numbers of gametangia per male inflorescence, presence of paraphyses in male inflorescences, and a much longer developmental time for male inflorescences. The realized cost of female reproduction from two communities dominated by S. caninervis was found to be lower than the realized cost of male sexual reproduction. Resource-limited reproduction was assessed by determining the frequency of sporophyte abortion, the age distribution of sporophyte abortions, and patterns of sporophyte abortion that may be density dependent. Among ten sexually reproducing populations, abortive sporophytes occurred at a frequency of 0.64. Abortive sporophytes averaged 8% the mass of mature sporophytes, and cohort sporophytes from the same individual female were found to abort in a density-dependent pattern. We conclude that the two assumptions, upon which the cost of sex hypothesis depends, are supported.

Journal Article↗

Mucosal immunity in the female reproductive tract: correlation of immunoglobulins, cytokines, and reproductive hormones in human cervical mucus around the time of ovulation.

Mucosal surfaces serve as the portal of entry for many viral, bacterial, and parasitic infections. Understanding the immunity at mucosal membranes is essential to enhancing protection and decreasing infections. To evaluate the humoral and cellular immunity in the female reproductive tract, 15 reproductive-age women with a history of regular, cyclic monthly menses were recruited for this study. The presence of immunoglobulins and cytokines in cervical mucus was correlated with the production of reproductive hormones in sera. Cervical mucus specimens were collected at each daily visit beginning on cycle day 8 and continuing for 5 days postovulation. Volunteers were monitored by daily urinary LH testing coupled with transvaginal ultrasonography to ascertain follicular collapse. The cervix was washed in sterile saline before aspirating the cervical mucus from the cervical canal. Collection volumes ranged between 50 and 800 microl and were considered to represent the total mucus produced. Estradiol displayed the characteristic biphasic pattern with a peak before ovulation and in the luteal phase. Both IgG (30 mg/dl) and IgA (15 mg/dl) had a biphasic pattern with peak immunoglobulin levels detected 1 day before the estradiol peak and increasing again just after ovulation. Peak interleukin 10 (40 pg/ml) levels corresponded precisely with estradiol peak levels just before ovulation. Peak interleukin 1beta (1.3 ng/ml) levels occurred approximately 1 day before the estradiol peak. No apparent pattern in interleukin 6 (150 pg/ml) could be ascertained. Our data suggest a correlation between the IgG and IgA immunoglobulin levels, interleukin 1beta and interleukin 10, in the female reproductive tract and estradiol levels in the circulation. The increase in immunoglobulins and cytokines occurs approximately 1 day before the peak estradiol production before ovulation. These data suggest a role for cytokines and hormones in the regulation of reproductive tract immunity.

Adult↗

Attitudes towards reproduction in Latin America. Teachings from the use of modern reproductive technologies.

The use of modern reproductive technology, such as in-vitro fertilization and its related procedures, has opened new areas of legal, religious and public concern. Thirty years ago, the development of effective methods to control procreation generated a debate on whether couples had the right to enjoy sex in the absence of its procreative effect. Today, assisted reproductive technology (ART) allows couples to have their own children in the absence of a direct intermediation of sex. The Catholic Church has reacted against both contraception and ART, and specific instructions have been directed to the public, the medical profession and legislators. In a recent survey, 88.4% of the population in Latin America claims to be Catholic; therefore, bioethical considerations and legal implications concerning intervention in reproduction are strongly permeated by the moral teachings of Catholicism. In 1996, 83 medical doctors and scientists, participating in the Latin American Network of Assisted Reproduction, produced a consensus document on ethical aspects and legal implications of ART. The document contains minimal ethical guidelines that Latin American professionals have decided to adhere to, even in the absence of legal regulations. This article examines how the medical profession, legislators and the public react to religious influence when confronted by difficult bioethical decisions such as the right to procreate.

Catholicism↗

Perspectives: the possible influence of assisted reproductive technologies on transgenerational reproductive effects of environmental endocrine disruptors.

Demasculinization by environmental endocrine-disrupting chemicals (EDCs) is observed in many animal species but less evident in humans. Rodent studies with gestational exposure to either the fungicide vinclozolin or the insecticide methoxychlor demonstrate impaired male fertility with abnormal DNA methylation patterns in spermatozoa. Once established, these epigenetic changes may be permanent and thus paternally passed to subsequent generations. Conclusive evidence of a similar phenomenon in humans has not been established, but several observations bring up the possibility. Some, but not all, studies show an increase in male genital abnormalities after prenatal EDC exposure. Other studies demonstrate sperm abnormalities in males with EDC contact, although it is unclear as to whether this is due to prenatal or postnatal exposure. Although not examined in males with EDC exposure, one study shows gamete DNA methylation abnormalities in males with severe oligospermia. A subsequent study failed to corroborate these findings. The use of assisted reproductive techniques including intracytoplasmic sperm injection has removed natural selection barriers thus enabling reproduction in males that would otherwise be sterile. This review explores the hypothesis that prenatal EDC exposure results in transgenerational male reproductive abnormalities propagated by the use of assisted reproductive technologies.

Animals↗

Reproductive choice: screening policy and access to the means of reproduction.

The practice of screening potential users of reproductive services is of profound social and political significance. Access screening lacks a defensible rationale, is inconsistent with the principles of equality and self-determination, and violates individual and group human rights. Communities that strive to function in accord with those principles should not permit access to screening, even screening that purports to be a benign exercise of professional discretion. Because reproductive choice is controversial, regulation by law my be required in most jurisdictions to provide effective protection for reproductive rights. In Canada, for example, equal access can, and should be, guaranteed by federal regulations imposing strict conditions on the licenses of fertility clinics.

Access to Information↗

Evaluation of the reproductive and developmental safety of cysteamine in the rat: effects on female reproduction and early embryonic development.

Cystinosis is an autosomal recessive metabolic disease in which the amino acid cystine accumulates in lysosomes due to a defect in lysosomal cystine transport. Cystinosis in infancy is associated with poor growth, muscle wastage, and death at about age 10 due to kidney failure. Treatment with cysteamine and kidney transplantation enables cystinotic girls to reach reproductive age and to be healthy enough to permit pregnancy. It is not known whether exposure to cysteamine will have adverse effects on reproduction in the human. It is also possible that some of the complications seen in cystinotic children could be avoided if a pregnant woman carrying a cystinotic fetus were given cysteamine. However, this treatment is not likely to occur until therapeutic exposures to cysteamine are judged to present no increased risk to the human fetus. As part of a larger investigation assessing the reproductive and developmental safety of cysteamine (as phosphocysteamine) using the rat, the two studies reported herein were performed. The first, a dose-finding study, led to the selection of 150 mg/kg/day as the highest dose of cysteamine used for the second and primary focus of this report. The second study involved the exposure of female rats to cysteamine from premating through day 6.5 postconception and assessment of female fertility and early embryonic development. Cysteamine was administered orally in doses of 0, 37.5, 75, 100, or 150 mg/kg/day. There were no clinical signs of maternal toxicity during the exposures of 2 to 5 weeks before successful mating. Animals in the 150 mg/kg/day group experienced a nonsignificant decrease in body weight gain during pregnancy to day 6.5 postconception, a significant increase in liver and spleen weights, and a significant increase in days to coitus--suggesting that a low level of toxicity was manifested. However, there were no adverse effects on reproductive performance with respect to conception and early embryonic development.

Animals↗

Lifetime reproductive success, longevity, and reproductive life history of female yellow baboons (Papio cynocephalus) of Mikumi National Park, Tanzania.

The relationship between longevity and lifetime reproductive success (LRS) was studied in free-ranging female baboons of Mikumi National Park, Tanzania. A severe population decline occurred between the 12th and 20th years of the study. The total sample consisted of 72 females born and reaching adulthood before the start of the population decline. There were 27 females who were adult at the start of the study and 45 who became adult within the 12 years prior to the decline. The subjects were studied until all 72 were dead and all of their offspring were either dead or at least six years old; this took 24 years. The relationship of longevity to LRS was statistically significant for the total sample and for both sub-samples, with 70% of the total variance in LRS accounted for by longevity. Longevity was linked to LRS via a chain of statistically significant relationships: The longer the life span, the longer the reproductive life; the longer the reproductive life, the more offspring produced; the more offspring produced, the higher the LRS. Mean LRS, life span, and reproductive longevity all differed between the two sub-samples. Since the sub-samples were time-linked to a population decline affecting longevity, either sub-sample separately would fail to reflect the broader picture. This illustrates the importance of appreciable sample sizes from long-term studies in helping understand the dynamics between life history estimates and ecological conditions in variable environments.

Animals↗

Reproductive endocrinology and weight change in relation to reproductive success in the magellanic penguin (Spheniscus magellanicus).

The Magellanic penguin is a colonial monogamous species that lays only a single clutch of two eggs per year. However, failed breeders remain at the colony and engage in nest building, fights, and copulations without relaying. The seasonal changes in reproductive hormones and body weight through the nesting cycle were studied, with respect to the reproductive success or failure of individuals. Body weight changed dramatically in both sexes through the season, in response to fasting during incubation, and high body weight in males at the onset of incubation was a strong predictor of eventual reproductive success. Circulating steroid hormones had a biphasic seasonal pattern, with elevated levels during the sexual phase of breeding (prior to egg laying), declining to low, stable levels during the parental phase after eggs were laid. Luteinizing hormone levels were elevated in females, but not in males, prior to egg laying. Both sexes responded to reproductive failure by increasing the secretion of testosterone, and females also increased the secretion of estradiol, a response that would be expected of a species that can renest following failure. However, renesting is extremely rare, and this hormonal response to failure may instead serve to promote maintenance of pair bonds and also territory ownership across years.

Animals↗

Assessing the reproductive performance of men co-infected with HIV-1 and hepatitis C undergoing assisted reproduction.

OBJECTIVE: To assess the reproductive performance of men co-infected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV-1) undergoing assisted reproduction. DESIGN: A retrospective analysis. SETTING: University-based assisted reproductive technology (ART) center. PATIENTS: We reviewed 217 consecutive ART cycles performed on 106 HIV-1 serodiscordant couples between August 1997 and March 2004, in which 28 men (26%) were seropositive for HCV and HIV-1 (group 1). MAIN OUTCOME MEASURES: Patient demographics and laboratory testing were compared to reproductive outcomes of men undergoing similar treatment but infected only with HIV-1 (group 2). RESULTS: Co-infected men and their partners were of similar age as men infected only with HIV-1. Comparing group 1 to group 2, like values were noted for HIV-1 viral loads [1,993 +/- 1,140 copies/ml (mean +/- SE) vs. 1,659 +/- 487 copies/ml]; CD4 counts (520 +/- 98 vs. 604 +/- 38 mm(-3)); and semen parameters. IVF performance and outcomes were similar, with fertilization rate (0.68 +/- 0.03 vs. 0.71 +/- 0.02); number of normally cleaving embryos (6.0 +/- 0.5 vs. 5.3 +/- 0.3); embryo implantation rate (0.27 +/- 0.04 vs. 0.2 +/- 0.02); and clinical pregnancy rate (40 vs. 29%). Although the male mortality rate was low in both groups, morbidity among co-infected men was significantly higher. Seven of 28 men (25%) had detectable HCV viral loads, and 14 (50%) had elevated liver function tests. CONCLUSION: Men co-infected with HCV and HIV-1 do reasonably well undergoing ART to prevent transmission of viruses to their partners and children.

Adult↗

A two-generation reproduction study to assess the effects of cows' milk on reproductive development in male and female rats.

OBJECTIVE: To examine whether the considerable quantities of increased female sex hormone levels found in modern milk as a result of modern dairy farming practices are safe for human consumption. DESIGN: Males and females of the P generation were maintained on a diet containing milk for 10 weeks before mating. Exposure to milk was continued up to the end of weaning of the F2b offspring. SETTING: Two-generation reproduction study. ANIMAL(S): Male and female Wistar Galas rats. INTERVENTION(S): P- and F1-generation rats were mated. MAIN OUTCOME MEASURE(S): Fertility, fecundity, and morphology and function of reproductive organs. RESULT(S): Although milk had growth-promoting effects in both parents and offspring, it caused no impairments in fertility, fecundity, or reproductive organ development in either generation. However, a whole litter from a dam of the P generation was born dead, three litters in total had a pup with skeletal abnormalities, and the AGD of F2a female pups was reduced. These events occurred only in the milk-treated rats. It is unknown whether these issues had any relevance to milk or only happened by chance. CONCLUSION(S): Further study is required to determine whether milk from pregnant cows is completely free from adverse effects on reproductive health.

Anal Canal↗

Associations between reproduction and maternal body weight: examining the component parts of a full reproductive cycle.

OBJECTIVE: Many transitional societies currently face both extremes of nutritional status, undernutrition and overnutrition. Women of reproductive age are at high risk of these conditions. The purpose of this review is to consider evidence for relationships between reproduction and nutritional status in women from societies of varying economic development, using body weight or weight-for-height as indicators of maternal nutritional status. DESIGN: The conceptual framework guiding this review is that the duration of the reproductive cycle varies as a function of its component parts, which include (i) pregnancy, (ii) lactation, (iii) the non-pregnant/non-lactating (NP/NL) interval or, possibly, (iv) an overlap between lactation and next pregnancy. All component parts of the complete cycle vary in length and are associated with changes in nutritional status. A variety of factors ('proximal and distal determinants') influence the duration of the component parts of the reproductive cycle. This framework is used to examine current knowledge of changes in maternal nutritional status during each of these parts. RESULTS: Women in affluent societies retain some weight with each pregnancy, beyond that of non-pregnant women. Women in less affluent societies retain less weight with each pregnancy. During lactation, women in both affluent and less affluent societies experience only modest weight loss. During the NP/NL interval, women in affluent societies tend to gain weight, whereas weight of women in less affluent societies is likely to fluctuate. CONCLUSIONS: We conclude that there is a dearth of information on certain parts of the cycle, particularly the periods of overlap of lactation with pregnancy and the NP/NL interval.

Adult↗

Reproductive surgery vs assisted reproductive technologies: selecting the correct alternative.

Many innovations have been made in advanced reproductive technologies (ART) over the past several years. These procedures now yield pregnancy rates of over 20% per cycle, rates that compare favorably to many types of reproductive surgery. Therefore, ART now represents a viable alternative for many patients suffering from infertility. As these pregnancy rates continue to rise, gynecologists will have to choose between ART and reproductive surgery for a larger number of patients. This article reviews the commonly performed reproductive surgical procedures and compares expected postoperative pregnancy rates to those of ART in order to help the gynecologist make this decision.

Female↗

What is the most relevant standard of success in assisted reproduction? The singleton, term gestation, live birth rate per cycle initiated: the BESST endpoint for assisted reproduction.

Assisted reproduction programmes do not report success consistently. Rates vary with the definition used. Success must reflect delivery of healthy babies, and the burden of treatment to couples. We report the singleton, term gestation, live birth rate of a baby per assisted reproductive technology cycle initiated for a large IVF programme. We defined assisted reproductive technology cycles as those initiated with the intention of oocyte collection. We examined cycles conducted through Monash IVF in 2001. All women with positive pregnancy tests had first trimester ultrasonography. Obstetric outcomes were recorded. All babies had neonatal examinations conducted by paediatricians. A total of 644 positive pregnancy tests were recorded in 2600 cycles; 509 showed fetal heart motion. Of 448 deliveries, 328 were singleton and 120 were multiple. There were 290 singleton deliveries at term gestation. In 2001, a couple had an 11.1% chance of delivering a singleton, term gestation, live baby per assisted reproductive technology cycle begun. We suggest that delivery of a single, term gestation, live baby per cycle initiated is the most relevant standard of success. This statistic was 11.1% at Monash IVF. We encourage programmes to report this BESST (Birth Emphasizing a Successful Singleton at Term) outcome.

Adult↗

The need for interaction between assisted reproduction technology and genetics: recommendations of the European Societies of Human Genetics and Human Reproduction and Embryology.

Infertility and reproductive genetic risk are both increasing in our societies because of lifestyle changes and possibly environmental factors. Owing to the magnitude of the problem, they have implications not only at the individual and family levels but also at the community level. This leads to an increasing demand for access to assisted reproduction technology (ART) and genetic services, especially when the cause of infertility may be genetic in origin. The increasing application of genetics in reproductive medicine and vice versa requires closer collaboration between the two disciplines. ART and genetics are rapidly evolving fields where new technologies are currently introduced without sufficient knowledge of their potential long-term effects. As for any medical procedures, there are possible unexpected effects which need to be envisaged to make sure that the balance between benefits and risks is clearly on the benefit side. The development of ART and genetics as scientific activities is creating an opportunity to understand the early stages of human development, which is leading to new and challenging findings/knowledge. However, there are opinions against investigating the early stages of development in humans who deserve respect and attention. For all these reasons, these two societies, European Society of Human Genetics (ESHG) and European Society of Human Reproduction and Embryology (ESHRE), have joined efforts to explore the issues at stake and to set up recommendations to maximize the benefit for the couples in need and for the community.

Journal Article↗

Potential significance of genomic imprinting defects for reproduction and assisted reproductive technology.

Recent studies suggest a possible link between human assisted reproductive technology and genomic imprinting disorders. Assisted reproductive technology includes the isolation, handling and culture of gametes and early embryos at times when imprinted genes are likely to be particularly vulnerable to external influences. Evidence of sex-specific differences in imprint acquisition suggests that male and female germ cells may be susceptible to perturbations in imprinted genes at specific prenatal and postnatal stages. Imprints acquired first during gametogenesis must be maintained during preimplantation development when reprogramming of the overall genome occurs. In this review, we will discuss both new developments in our understanding of genomic imprinting including the mechanisms and timing of imprint erasure, acquisition and maintenance during germ cell development and early embryogenesis as well as the implications of this research for future epigenetic studies in reproduction and assisted reproductive technology.

Angelman Syndrome↗

Cost of reproduction in a long-lived bird: incubation effort reduces immune function and future reproduction.

Life-history theory predicts that increased current reproductive effort should lead to a fitness cost. This cost of reproduction may be observed as reduced survival or future reproduction, and may be caused by temporal suppression of immune function in stressed or hard-working individuals. In birds, consideration of the costs of incubating eggs has largely been neglected in favour of the costs of brood rearing. We manipulated incubation demand in two breeding seasons (2000 and 2001) in female common eiders (Somateria mollissima) by creating clutches of three and six eggs (natural range 3-6 eggs). The common eider is a long-lived sea-duck where females do not eat during the incubation period. Mass loss increased and immune function (lymphocyte levels and specific antibody response to the non-pathogenic antigens diphtheria and tetanus toxoid) was reduced in females incubating large clutches. The increased incubation effort among females assigned to large incubation demand did not lead to adverse effects on current reproduction or return rate in the next breeding season. However, large incubation demand resulted in long-term fitness costs through reduced fecundity the year after manipulation. Our data show that in eiders, a long-lived species, the cost of high incubation demand is paid in the currency of reduced future fecundity, possibly mediated by reduced immune function.

Analysis of Variance↗