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[Fluctuation in the concentration of sex steroids and aflatoxin B1 in the seminal plasma of boars and its relation to sperm production].

The concentration of testosterone, 17-beta oestradiol and aflatoxin B1 were studied in the semen plasma of 21 boars of four breeds for the period of twelve months. The following spermiological parameters were investigated: semen volume, sperm concentration, percentage of abnormal spermatozoa, and survival of spermatozoa. The fertilizing capacity of ejaculates was evaluated according to the conception rate of sows and gilts after the first insemination, according to the average number of piglets per litter and average number of live-born piglets per litter. The highest aflatoxin B1 residues in sperm were recorded in March to May and were related with aflatoxin concentration in feed ration. The group of boars with fertility disorders had more aflatoxin in their sperm (up to 100 pmol . l-1), lower sperm concentration, lower survival of spermatozoa, and a larger proportion of abnormal spermatozoa. The year season had a significant influence on the concentration of the hormones. The highest average value of testosterone (10.2 +/- 1.28 nmol) was obtained in autumn and lower values were recorded in winter. The changes in 17-beta estradiol concentration were similar to the changes in testosterone content, with the maximum value in November (0.249 nmol X 1(-1]. The boars with reproduction disorders had a significantly lower concentration of 17-beta oestradiol. Significant correlations were found between the concentration of the hormones, semen volume, and sperm concentration. 17-beta oestradiol also had a significant positive correlation to abnormal spermatozoa and to the activity of aspartate aminotransferase.

Aflatoxin B1↗

Metformin treatment of PCOS during adolescence and the reproductive period.

Insulin resistance is a common feature of PCOS. Hyperinsulinemia has been causally linked with all features of the syndrome, such as hyperandrogenism, reproductive disorders, and metabolic disturbances. Several insulin-sensitizing agents have been tested in the management of PCOS. Metformin is the only drug currently in widespread clinical use for PCOS. In a high percentage of patients, treatment with metformin is followed by regularization of the menstrual cycle, less pronounced hyperandrogenism and cardiovascular risk factors, and some improvement in the response to therapies aimed at induction of ovulation. In adolescent girls who are anovulatory and moderately obese, metformin administration can have a normalizing effect on multiple aberrations within the endocrine-metabolic status. During the reproductive period, metformin administration can improve reproductive function and the establishment of pregnancy. A role of metformin in prevention of gestational diabetes and hypertensive complications of pregnancy has yet to be shown. Finally, any real benefit of insulin-lowering treatment in terms of lesser cardiovascular risk in women with PCOS women remains to be demonstrated.

Adolescent↗

[Effects of bisphenol A on the placental function and reproduction in rats].

OBJECTIVES: The aim of this study was to investigate the effects of bisphenol A (BPA), an estrogen-like environmental endocrine disrupter, on the placental function and reproduction in rats. The mRNA levels of the placental prolactin-growth hormone(PRL-GH) gene family, placental trophoblast cell frequency and reproductive data were analyzed. METHODS: The pregnancies of F344 Fisher rats (160 g +/-20 g) were detected by the presence of the copulatory plug or sperm in the vaginal smear, which marked Day 0 of pregnancy. Pregnant rats were divided into three groups. The control group was intraperitoneally injected with a sesame oil vehicle. The two remaining groups were injected with 50 or 500 mg/kg B.W/day of BPA, resuspended in sesame oil, on either days 7 to 11 or 16 to 20 of pregnancy, with the rats sacrificed on either day 11 or 20, respectively. The mRNA levels of PRL-GH and Pit-1a and b isotype genes were analyzed by Northern blot hybridization and reverse transcription-polymerase chain reaction. The hormone concentrations were analyzed by radioimmunoassay, and the frequency of the placental trophoblast cells observed by a histochemical study. Reproductive data, such as the placental weight and litter size, were surveyed on day 20. The fetal weight was surveyed for 4 weeks after birth. A statistical analysis was carried out using the SAS program (version 8.1). RESULTS: The mRNA levels of the PRL-GH gene family, such as placental lactogen I, Iv and II, prolactin like protein A, C and Cv, and decidual prolactin-related protein were significantly reduced due to BPA exposure. The mRNA levels of the Pit-1a and b isotype genes, which induce the expression of the PRL-GH gene family in the rat placenta, were also reduced due to BPA exposure. The PL-Iv and PL-II concentrations were reduced in the BPA exposed group. During the middle to last stage of pregnancy (Days 11-20), a high dose of BPA exposure reduced the frequency of spongiotrophoblast cells, which are responsible for the secretion of the PRL-GH hormones. Reproductive data, such as the placental and fetal weights and the litter size, were reduced, but that of the pregnancy period was extended in the BPA exposed compared to the control group. CONCLUSIONS: BPA disrupts the placental functions in rats, which leads to reproductive disorders.

Animals↗

Genetic dissection of mammalian fertility pathways.

The world's population is increasing at an alarming rate and is projected to reach nine billion by 2050. Despite this, 15% of couples world-wide remain childless because of infertility. Few genetic causes of infertility have been identified in humans; nevertheless, genetic aetiologies are thought to underlie many cases of idiopathic infertility. Mouse models with reproductive defects as a major phenotype are being rapidly created and discovered and now total over 200. These models are helping to define mechanisms of reproductive function, as well as identify potential new contraceptive targets and genes involved in the pathophysiology of reproductive disorders. With this new information, men and women will continue to be confronted with difficult decisions on whether or not to use state-of-the-art technology and hormonal treatments to propagate their germline, despite the risks of transmitting mutant genes to their offspring.

Animals↗

The ovarian renin-angiotensin system in reproductive physiology.

The identification of the presence of prorenin, renin, angiotensinogen, angiotensin-converting enzyme, angiotensin II (Ang II), and Ang II receptors in the ovary suggests that there is a functional ovarian renin-angiotensin system (RAS). It could play a significant role in such areas of ovarian physiology as follicular development, steroidogenesis, oocyte maturation, ovulation, and follicle atresia. Expression of the ovarian RAS is regulated by gonadotropins. Ang II, a bioactive octapeptide of RAS, has important effects as a paracrine/autocrine regulator at different stages of the reproductive cycle. Ang II modulates ovarian steroidogenesis and formation of the corpus luteum and also stimulates oocyte maturation and ovulation via Ang II receptors on granulosa cells. In addition, increasing evidence demonstrates that Ang II is a major factor in regulating the function of atretic follicles. In any physiologic system, aberrations result in the development of pathologic states. Disturbances in the ovarian RAS can be the cause or the result of such reproductive disorders as polycystic ovary syndrome, ovarian hyperstimulation syndrome, ovarian tumors, and ectopic pregnancy. Data support the concept of an active and regulated RAS in ovarian follicles. Species differences observed in the expression of ovarian RAS suggest varying functional roles among species with respect to ovarian physiology.

Angiotensin II↗

Freezing immature oocytes.

The establishment of a long-term preservation system for mammalian oocytes is important for the development of both biological and medical sciences. A number of efforts have been made to develop this system. In human reproductive medicine, the development of an oocyte cryopreservation system can improve the efficacy of the current assisted reproductive technology (ART) for infertile patients with severe reproductive disorders. In this article, the technical development of cryopreservation programs for human oocytes and its biological background were reviewed. Clinical outcome after the use of this technology was further introduced.

Cell Culture Techniques↗

[Environmental factors which impair male fertility].

Introduction of new technologies involving many chemicals does not remain free from the effect on the human health. Occupational acute poisoning is rare now-a-days, but we often face many problems arising out of the late sequel to exposures, such as mutations, neoplasms or reproduction disorders. Numerous research institutes of occupational medicine are involved in the evaluation of the effect of environmental factors on the workers' health. Many recent publications emphasise that the quality of the human semen is gradually decreasing which is manifested by the lower number of spermatozoons (1 cm3) semen, a higher proportion of morphologically impaired spermatozoons and a higher per cent of motile spermatozoons. The quality of the semen is affected not only by the hazards present in the general environment, but also by the factors occurring in the work environment. Occupational exposure induces sometimes infertility of couples but more often impairs the reproduction, and this is one of important issues which be addressed by occupational medicine.

Abortion, Spontaneous↗

Effects of GnRH administered to cows at the onset of estrus on timing of ovulation, endocrine responses, and conception.

Two experiments examined effects of GnRH administered within 3 h after onset of estrus (OE) on ovulation and conception in dairy cows. In experiment 1, 46 cows received either saline, 250 microg of GnRH, or 10 microg of the GnRH analogue, Buserelin. Cows were observed for estrus, blood samples were collected, and ovulations were monitored by ultrasound. In controls, 76% of cows had intervals from estrus to ovulation of < or = 30 h and 24% had intervals > 30 h. Treatment with either GnRH or GnRH analogue (data combined) increased magnitude of LH surges and decreased intervals from estrus to LH surge or to ovulation. Treated cows all ovulated < or = 30 h after OE. Among control cows, plasma estradiol concentrations before estrus correlated positively with amplitudes of LH surges. Higher plasma progesterone was observed in the subsequent estrous cycle in GnRH-treated cows compared to control cows with delayed ovulations. Experiment 2 included 152 primiparous and 211 multiparous cows in summer and winter. Injection of GnRH analogue at OE increased conception rates (CR) from 41.3 to 55.5% across seasons. In summer, GnRH treatment increased CR from 35.1 to 51.6%. Across seasons, GnRH increased CR from 36.0 to 61.5% in cows with lower body condition at insemination and GnRH increased CR (63.2 vs. 42.2%) in primiparous cows compared to controls. Use of GnRH eliminated differences in CR for cows inseminated early or late relative to OE and increased CR in cows having postpartum reproductive disorders. In conclusion, GnRH at onset of estrus increased LH surges, prevented delayed ovulation, and may increase subsequent progesterone concentrations. Treatments with GnRH increased conception in primiparous cows, during summer, and in cows with lower body condition.

Animals↗

Review on the toxicity, occurrence, metabolism, detoxification, regulations and intake of zearalenone: an oestrogenic mycotoxin.

Zearalenone (ZEA) is a mycotoxin produced mainly by fungi belonging to the genus Fusarium in foods and feeds. It is frequently implicated in reproductive disorders of farm animals and occasionally in hyperoestrogenic syndromes in humans. There is evidence that ZEA and its metabolites possess oestrogenic activity in pigs, cattle and sheep. However, ZEA is of a relatively low acute toxicity after oral or interperitoneal administration in mice, rat and pig. The biotransformation for ZEA in animals involves the formation of two metabolites alpha-zearalenol (alpha-ZEA) and beta-zearalenol (beta-ZEA) which are subsequently conjugated with glucuronic acid. Moreover, ZEA has also been shown to be hepatotoxic, haematotoxic, immunotoxic and genotoxic. The exact mechanism of ZEA toxicity is not completely established. This paper gives an overview about the acute, subacute and chronic toxicity, reproductive and developmental toxicity, carcinogenicity, genotoxicity and immunotoxicity of ZEA and its metabolites. ZEA is commonly found on several foods and feeds in the temperate regions of Europe, Africa, Asia, America and Oceania. Recent data about the worldwide contamination of foods and feeds by ZEA are considered in this review. Due to economic losses engendered by ZEA and its impact on human and animal health, several strategies for detoxifying contaminated foods and feeds have been described in the literature including physical, chemical and biological process. Dietary intakes of ZEA were reported from few countries from the world. The mean dietary intakes for ZEA have been estimated at 20 ng/kgb.w./day for Canada, Denmark and Norway and at 30 ng/kgb.w./day for the USA. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) established a provisional maximum tolerable daily intake (PMTDI) for ZEA of 0.5 microg/kg of body weight.

Animal Feed↗

Association between endometriosis, dysplastic naevi and history of melanoma in women of reproductive age.

Women with melanoma and its precursor lesions, dysplastic naevi, have a higher prevalence of reproductive disorders than women without melanotic lesions. This association appears strongest among young women with dysplastic naevi and endometriosis. The purpose of this study was to evaluate patients with laparoscopy-confirmed endometriosis for the presence of dysplastic naevi. A total of 66 endometriosis patients and 35 controls completed a detailed questionnaire and underwent an extensive dermatological examination for the presence of dysplastic naevi. In all, 41% of patients aged < or = 32 years had dysplastic naevi, compared with 8% of controls (P = 0.038). In addition, 29% of patients with endometriosis reported a family history of melanoma compared with 10% of controls (P = 0.039). This study demonstrated an association between endometriosis and dysplastic naevi in younger women of reproductive age and found an associated family history of melanoma among endometriosis patients. These observations may be useful in the evaluation and care of young women by both gynaecologists and dermatologists.

Adult↗

[Endocrine disruption agents: environment, health, public policies, and the precautionary principle].

The already substantial body of evidence and growing web of suspicions as to the scale and severity of the cascade effects of endocrine disrupters (related to persistent organic pollutants or POPs) on the health of ecosystems and humans have sparked such concern that in June 1998, representatives of 94 countries meeting in Montreal under the aegis of UNEP signed a draft international agreement to phase out the most harmful POPs. Related to particular persistent organic pollutants--toxic semi-volatile and persistent chemical compounds now found everywhere in the environment, such as BPCs, organochlorine pesticides, dioxins and furans, that build up in the bodies of organisms that consume other contaminated organisms along the food chain--endocrine disrupters are strongly suspected of affecting the health of animals and adversely impacting the health, fertility and even intellectual faculties of humans. For example, very low-level exposure to some POPs is associated with some hormone-dependent cancers, damage to the central and peripheral nervous systems, impaired immune system function, reproductive disorders and developmental disruptions in newborns and infants, who can be affected in utero or through breast-feeding. Considering the extreme complexity of the scientific and socio-economic effects of POP-related endocrine disrupters, there are those who, advocate a wait-and-see approach, claiming that there is not enough formal scientific proof. There are others who use the available evidence to advance the research, press for bans on incriminated substances and look for global, integrated and viable alternatives. And there are other still who, with careless disregard for the Precautionary Principle, are quite prepared to talk about the perverse effects of POPs in order to justify the increased use of artificial means of reproduction or the replacement of chemical pesticides by pest-resistant genetically modified organisms (GMOs), thereby opening the door to "solutions" that are potentially more biologically and ethically dangerous than the problems they purport to remedy. This paper provides an overview of the current understanding of the main sources and suspected effects of POPs on animal life and human health, explores the complexity of the scientific, economic and political issues involved in any international process to do away with the incriminated products, discusses the risks and perverse consequences of some of the proposed alternatives, and stresses the importance, in the light of these risks and consequences, of placing renewed emphasis on public and environmental health approaches based on the Precautionary Principle.

Endocrine System Diseases↗

[Hormonal correction in combined therapy of temporomandibular joint dysfunction in women].

Pain dysfunction syndrome of the temporomandibular joint (TMJ) in women is often accompanied by mammary and reproductive disorders associated with endocrine disturbances. 30 female patients aged 19-35 years suffering from of the pain dysfunction syndrome TMJ combined with intact dentition and orthognathic occlusion were studied. Dental examination was followed by gynecologic examination. According to the treatment the patients were divided into 2 groups. Group I included women who were administered conventional treatment (orthopedic treatment, drug and physiotherapy). In group II patients conventional therapy was also combined with monophase oral contraceptive "Femoden". Efficacy of treatment in group I was 46.67%; while group II patients showed a 100% favourable effect. Besides, combination of dental and gynecologic therapy was found to exert a 2.1 times more stable clinical effect us compared to conventional treatment. Hormone correction in women with reproductive pathology results in prolonged control of the pain dysfunction syndrome TMJ due to steroid normalization (hypothalamic, hypophysial, ovary steroid normalization) and has no side effects.

Adult↗

[Delayed health effects of pesticides: review of current epidemiological knowledge].

The use of pesticides has extensively grown in the last decades, regardless of the economic level of the countries. This led to great improvements in agriculture but also a threat for human health. Short term effects are quite well known through approval procedures for pesticides. On the other hand, long term effects are not properly assessed. A review of epidemiologic knowledge is presented here. Epidemiologic studies on pesticides have found associations with long-term effects on health mainly in three fields: cancer (especially hematological cancer), neurotoxic effects (polyneuropathy, neuro-behavioral hazards, Parkinson's disease), and reproductive disorders (infertility, birth defects, adverse pregnancy outcomes, perinatal mortality). These conclusions have been obtained despite difficulties in exposition assessment due to the retrospective nature of the studies. But the continuous development of pesticide use in agriculture, and also in domestic environment, emphasizes the need for epidemiologic studies on long-term effects of pesticides relying on accurate exposure assessment.

Environmental Exposure↗

Effects of the high growth (hg) mutation on reproduction in high growth (HG) female mice.

Reproductive performance was characterized in females of a line of mice homozygous for a recessive mutation with a major effect on growth, the high growth (hg) mutation. Specifically, the age at onset of puberty, length of the estrous cycle, ovulation rate, and gestation length in high growth (HG) mice were determined and compared with control mice. HG females reached puberty at an age similar to control animals, exhibited normal ovulation rates and estrous cycle length, but had a shorter length of estrus. Number of fetuses at Day 17 of gestation was greater and gestation length was longer in HG females. The HG females exhibited a variety of reproductive disorders, including increased incidence of repeated detection of mating plugs without intervening pregnancy ("replug"), increased incidence of repeated detection of mating plugs within an interval of 1-8 days without intervening pregnancy ("recycle"), increased interval between pairing with a male and detection of the first mating plug, increased interval between mating and conception, increased postnatal mortality, decreased litter size, and increased incidence of vaginal septum.

Animals↗

Porcine circovirus diseases.

Porcine circovirus type 2 (PCV2) is a member of the family Circoviridae, a recently established virus family composed of small, non-enveloped viruses, with a circular, single-stranded DNA genome. PCV2, which is found all over the world in the domestic pig and probably the wild boar, has been recently associated with a number of disease syndromes, which have been collectively named porcine circovirus diseases (PCVD). Postweaning multisystemic wasting syndrome (PMWS), porcine dermatitis and nephropathy syndrome (PDNS) and reproductive disorders are the most relevant ones. Among them, only PMWS is considered to have a severe impact on domestic swine production. PMWS mainly affects nursery and/or fattening pigs; wasting is considered the most representative clinical sign in this disease. Diagnosis of this disease is confirmed by histopathological examination of lymphoid tissues and detection of a moderate to high amount of PCV2 in damaged tissues. Since PMWS is considered a multifactorial disease in which other factors in addition to PCV2 are needed in most cases to trigger the clinical disease, effective control measures have focused on the understanding of the co-factors involved in individual farms and the control or elimination of these triggers. PDNS, an immuno-complex disease characterized by fibrino-necrotizing glomerulonephritis and systemic necrotizing vasculitis, has been linked to PCV2, but a definitive proof of this association is still lacking. PCV2-associated reproductive disease seems to occur very sporadically under field conditions, but it has been characterized by late-term abortions and stillbirths, extensive fibrosing and/or necrotizing myocarditis in fetuses and the presence of moderate to high amounts of PCV2 in these lesions. Taking into account that scientific information on PCV2 and its associated diseases has been markedly expanded in the last 8 years, the objective of this review is to summarize the current state of knowledge of the most relevant aspects of PCV2 biology and PCVD.

Animals↗

Targeted disruption of luteinizing hormone beta-subunit leads to hypogonadism, defects in gonadal steroidogenesis, and infertility.

Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) act on gonadal cells to promote steroidogenesis and gametogenesis. Clarifying the in vivo roles of LH and FSH permits a feasible approach to contraception involving selective blockade of gonadotropin action. One way to address these physiologically important problems is to generate mice with an isolated LH deficiency and compare them with existing FSH loss-of-function mice. To model human reproductive disorders involving loss of LH function and to define LH-responsive genes, we produced knockout mice lacking the hormone-specific LHbeta-subunit. LHbeta-null mice are viable but demonstrate postnatal defects in gonadal growth and function resulting in infertility. Mutant males have decreased testes size, prominent Leydig cell hypoplasia, defects in expression of genes encoding steroid biosynthesis pathway enzymes, and reduced testosterone levels. Furthermore, spermatogenesis is blocked at the round spermatid stage, causing a total absence of the elongated spermatids. Mutant female mice are hypogonadal and demonstrate decreased levels of serum estradiol and progesterone. Ovarian histology demonstrates normal thecal layer, defects in folliculogenesis including many degenerating antral follicles, and absence of corpora lutea. The defects in both sexes are not secondary to aberrant FSH regulation, because FSH levels were unaffected in null mice. Finally, both male and female null mice can be pharmacologically rescued by exogenous human chorionic gonadotropin, indicating that LH-responsiveness of the target cells is not irreversibly lost. Thus, LHbeta null mice represent a model to study the consequences of an isolated deficiency of LH ligand in reproduction, while retaining normal LH-responsiveness in target cells.

Animals↗

Factors affecting the fertility of high producing dairy herds in northeastern Spain.

Infertility has been often correlated to a rising milk yield in high producing dairy cattle. The aim of the present study was to evaluate, using logistic regression procedures, the effects of several management indicators on the fertility of four dairy herds in northeastern Spain. Data derived from 10,965 artificial insemination (AI). The factors examined were: herd, milking frequency (three versus two milkings per day), lactation number, previous twinning and disorders such as placenta retention and pyometra, milk production at AI, the inseminating bull, season (warm versus cool period) and year effects, AI technician and repeat breeding syndrome (cows undergoing four or more AI). Our findings indicated no effects on fertility of the herd, year of AI, previous twining, placenta retention and pyometra and milk production at AI. Based on the odds ratios, the likelihood of pregnancy decreased: in cows milked three times per day (by a factor of 0.62); for each one unit increase in lactation number (by a factor of 0.92); for inseminations performed during the warm period (by a factor of 0.67); in repeat breeder cows (by a factor of 0.73); and when 3 of the 45 inseminating bulls included in the study were used (by factors of 0.35, 0.43 and 0.44, respectively). Of the 13 AI technicians participating in the study, 3 were related to a fertility rate improved by odds ratios of 1.86, 1.84 and 1.30, respectively, whereas 2 technicians gave rise to fertility rates reduced by odds ratios of 0.64 and 0.49, respectively. Under our study conditions, management practices were able to compensate for the effects of previous twining and reproductive disorders such as placenta retention and pyometra. However, fertility was significantly affected by the factors milking frequency, AI technician, inseminating bull, repeat breeding syndrome, lactation number and AI season.

Animals↗

The effect of persistent chlorinated hydrocarbons on the secretion of estradiol and progesterone by bovine granulosa cells in vitro.

The role of persistent chlorinated hydrocarbons (PCH) in the reproductive disorders in ruminants is not well documented. In the present study we have examined the effect of these compounds and their metabolites on the secretion of estradiol (E2) and progesterone (P4) by bovine granulosa cells in vitro. Granulosa cells were isolated from large follicles (> or = 8 mm diameter) by gently washing the internal follicle wall. Aliquots of approximately 4 X 10(5) viable granulosa cells in 0.5 ml medium were cultured at 37 degrees C in an atmosphere of 5% CO2 and 95% air. Granulosa cells were cultured for 96h in a medium containing different concentrations (10(-1)-10(-4) ng/ml) of a PCH combination. Estradiol and progesterone were measured in unextracted granulosa cell culture medium by Enzyme Immunoassay (EIA). The exposure of granulosa cells to a combination of these organochlorine compounds in vitro results in a slight decrease of estradiol secretion only at the highest studied concentration of the PCH combination. However, the secretion of progesterone by these cells was seriously decreased, even by concentrations found in ovaries from animals kept under natural environmental conditions. The in vitro culture system of granulosa cells from preovulatory follicles may be useful in screening toxic effects of pesticides in animal reproduction.

Animals↗