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PubMed1986

Delayed development of reproductive functions and alteration of dopamine receptor binding in hypothalamus of rats exposed prenatally to phenytoin and phenobarbital.

Previous work in experimental animals treated prenatally with phenobarbital revealed reproductive changes in the offspring. Little has been reported on the effect of phenytoin or a combination of both drugs. 75 Pregnant Sprague-Dawley rats were administered either phenytoin (Na salt) at 20, 40 or 80 mg/kg orally (p.o.), phenobarbital (Na salt) at 20, 40 or 80 mg/kg subcutaneously (s.c.) or a combination of both drugs at the same doses daily from 5 to 20 days of pregnancy (4-12 rats/dose level). 24 Control rats received 1% methylcellulose p.o. and distilled water s.c. Regularity of estrous cycles was decreased in all treated groups, with the phenytoin group being most affected. The binding of [3H]spiroperidol, known to label dopamine receptors, was decreased in the hypothalamus of all drug-treated groups, indicating that the alteration in neuroendocrine function may be responsible for the above effects. Data suggest that prenatal exposure of rats to anticonvulsant drugs could lead to reproductive disorders.

Animals↗
PubMed2006

Genetic and environmental origins of obesity relevant to reproduction.

Obesity has a negative impact on reproductive health, particularly in women with polycystic ovarian syndrome (PCOS). Obesity itself is the product of both genetic and environmental influences, although the current 'epidemic' of obesity is largely related to changes in diet and lifestyle. Single gene defects leading to obesity and disordered reproductive function are rare but can are informative about metabolic pathways involved in appetite regulation. There is good evidence that PCOS has an important genetic background, which probably involves the interaction of several genes. The phenotype of PCOS and its impact on reproductive function is profoundly affected by obesity, which, in turn has both genetic and environmental influences. Understanding the genetic basis of PCOS is important but improvements in diet and lifestyle are the best means of improving reproductive function.

Chromosomes, Human, Pair 19↗
PubMed1996

Infertility and subfertility in Norwegian women aged 40-42. Prevalence and risk factors.

BACKGROUND: There are few population estimates of the prevalence of infertility that also include some information about medical conditions and social classification of study objects. This is a study of 4034 out of a total of 5139 (78% of all invited) women in one county of Norway. METHODS: All female inhabitants born 1950 to 1952 living in the county were invited to participate in a health screening. The screening comprised a clinical screening and two questionnaires; one about reproductive history and infertility. RESULTS: This survey found permanent primary infertility in 2.6% of the women. Subfertility, as at least one year's delay of pregnancy, was reported by 7.7%. A history of different reproductive problems was associated with impaired fertility. Thirty-two percent of primary infertile women had a history of PID, 13% had experienced amenorrhea and almost 40% reported premenstrual tension, compared with lower frequencies in women with normal fertility (11.0%, 3.3% and 29.4% respectively). CONCLUSIONS: Up to 10% of the female population may experience infertility at one stage in their reproductive career. Clinicians should pay special attention to women presenting any genital or reproductive disorder regarding risks for future fertility impairment.

Adult↗
PubMed2000

Suboptimal reproductive performance of dairy cattle kept in smallholder herds in a rural highland area of northern Tanzania.

The objectives of the present study were to assess the reproductive performance and cumulative incidence risk of reproductive disorders and to compare the success of artificial insemination (AI) to natural service (by handmating; NS) in dairy cattle kept in smallholder herds under a zero-grazing system in a rural highland area of Tanzania. Data on occurrence of all normal and abnormal reproductive events were collected for 215 adult animals belonging to 74 households. The median and range of the intervals: intercalving, calving to first service, and calving to pregnancy were 477 (335-860), 154 (38-486) and 206 (61-567) days, respectively. Breed and parity did not affect the reproductive parameters (P>0.05). However, cows in the milked group had a shorter median calving interval than those in the suckled group (P<0.001). The overall percentage pregnant and the percentage pregnant to first service were higher in the NS than in the AI group (49 vs. 32%; P=0.007) and (67 vs. 25%; P<0.001), respectively. The median numbers of services per pregnancy were not different between the AI (3) and NS (2) groups (P=0.17). The cumulative incidence risk of abortion, dystocia, prolapse, retained fetal membranes, mastitis, milk fever and cyclic non-breeders were 16.0, 1.7, 2.5, 4.2, 5.0, 1.7, and 6.1%, respectively. Hoof overgrowth (4.6%) and hoof deviation (4.6%) were the most-frequent digital problems. We concluded that reproductive parameters and cumulative incidence risk of abortion show suboptimal reproductive performance in rural-based, zero-grazed smallholder dairy herds in Tanzania particularly those using AI.

Abortion, Spontaneous↗
PubMed2003

Effects of presynchronization during the preservice period on subsequent ovarian activity in lactating dairy cows.

Among the strategies aimed at overcoming difficulties in estrus detection in dairy herds, presynchronization with two PGF2alpha treatments 14 days apart before a timed AI protocol has been related to a significant increase in pregnancy rates. The aim of the present study was to evaluate the effects of presynchronization during the preservice period on subsequent ovarian activity in clinically normal lactating dairy cows. A second objective was to evaluate the incidence of reproductive disorders on Day 50 postpartum. Depending on the chronological order of parturition, cows were alternately assigned to a control (n=102) or treatment (n=101) group. Animals in the treatment group were administered two cloprostenol treatments 14 days apart, beginning on Day 22 postpartum. The reproductive tract of each animal was examined ultrasonographically on Days 43 and 50 postpartum to monitor ovarian structures and uterine contents. Blood samples were collected on Day 50 for progesterone determination. Cows were inspected for signs of estrus between Days 50 and 71 postpartum and were then inseminated. Follicular persistence rates were similar in the presynchronized (14.9%) and control (13.7%) groups. Cows in the presynchronized group showed a lower metritis-pyometra rate (0% < 3.9%; P=0.045); a lower ovarian cyst rate (3% < 10.8%; P=0.03); a higher luteal activity rate (progesterone concentrations>/=1ng/ml) on Day 50 postpartum (76.2% > 52.9%; P=0.0005); a higher estrus detection rate (73.3% > 47.1%; P<0.0001); a higher ovulation rate (72% > 44%; P<0.0001) and a higher pregnancy rate (29.7% > 15.7%; P=0.02) than controls. Our results indicate that presynchronization during the preservice period reduces the incidence of ovarian cysts and metritis-pyometra determined on Day 50, and improves ovarian activity from Days 50 to 71 postpartum along with pregnancy rates in clinically normal lactating dairy cows.

Animals↗
PubMed2002

Experimental inoculation of late term pregnant sows with a field isolate of porcine reproductive and respiratory syndrome vaccine-derived virus.

The use of a live attenuated porcine reproductive and respiratory syndrome virus (PRRSV) vaccine in piglets has been associated with reproductive disorders in non-vaccinated sows. Vaccine-derived virus (VDV) has been isolated from foetuses, stillborn pigs, and dead piglets, indicating that the live vaccine spread from vaccinated piglets to non-vaccinated sows, and that the virus might be implicated in the severe reproductive problems observed. In the present study, one such VDV isolate was used to experimentally infect pregnant sows in the last trimester. The chosen isolate, which had more than 99.6% identity to the attenuated vaccine virus, originated from the lungs of a stillborn pig from a swine herd with a sudden high level of stillborn pigs and increased piglet mortality in the nursing period. Intranasal inoculation of sows with the virus isolate resulted in congenital infection, foetal death, and preweaning pig mortality. As such, the present study showed that vaccine-derived PRRSV can cause disease in swine consistent with PRRS.

Animals↗
PubMed2006

A new perspective on management of reproduction in dairy cows: the need for detailed metabolic information, an improved selection index and extended lactation.

For lactating dairy cows, we need management tools, that are "clean, green and ethical", cost-effective and easy to use. Specific tools are needed for artificial insemination (AI) after oestrus detection within a few months of calving, and for managing the complex nutritional requirements of cows between successive calvings. Assessment of energy deficit by measurement of body condition score (BCS) has been useful in the past but we now need more sophisticated ways to measure the relationship between adipose tissue and fertility. For this reason, we have focused our attention on the cells of the adipose tissue, the adipocytes, and the role of the hormone that they produce, leptin. This hormone affects pulsatile LH release and, in dairy cows, it seems to be linked to the first postpartum ovulation. Adipocytes are always sensing energy status and they control leptin secretion dynamically, so blood leptin concentrations can change acutely, even when there is no detectable change in BCS. Leptin secretion seems to be determined by the secretory activity of each adipocyte as well as the total mass of adipocytes in the body of the animal (as measured by BCS). The strong relationship between BCS, leptin concentration and reproductive function in dairy cows suggests that we should reconsider the interval of the recovery from prepartum and postpartum damages, the need for high milk yields at the last lactation causing the dry-off stress and the subsequent troubles. We should also re-assess the current drive to reduce calving interval because milk yields during the early stages of lactation are economically very important but high yields seem to cause several metabolic and reproductive disorders in modern dairy cows. In general, the thinking has been that calving interval must be short because short intervals are more profitable. However, if we remember that main product from dairy cows is milk and that a short calving interval is very difficult without reproductive problems, then a longer calving interval might be more sensible and also more profitable. We have example of an extended calving interval in Japan, Supercows which are very rare cows yielding remarkable high milk. Finally, we probably need to improve dairy cows genetically if we are to achieve the goal of "clean, green and ethical" dairy farming. This paper reviews data relevant to these strategies and we conclude that more basic and applied research will be required if we are to find ways to reach that goal.

Animal Husbandry↗
PubMed1980

Long-term performance and health cows experimentally exposed to polybrominated biphenyls.

Fifteen Holstein cows were studied for up to 15 00 days to determine whether exposure to polybrominated biphenyls produced latent or subtle toxicosis not evident in previous acute or short studies. Animals for these long studies came from three groups given 0, .25, or 250 mg of fireMaster BP-6 per day for 60 days in 1975. Another group that received 250 mg of BP-6 for 180 or 202 days in 1976 also was studied. Individual animals were in their second, third, or fourth lactations. Milk production was not different among experimental groups, and mature body weights were similar. Increases in the amount or duration of exposure did not increase number of infections, dysfunctions, or general injuries. Exposure to 250 mg/day for 60, 180, or 202 days increased frequencies of reproductive disorders at parturition, particularly related to and following a high incidence of dystocia. A contributing factor to dystocia was larger birth weights of calves from cows exposed to 250 mg daily as compared to calves from cows exposed to 0 or .25 mg polybrominated biphenyls. Although reproductive dysfunctions required more veterinary care, numbers of services per conception were not different among groups.

Animals↗
PubMed2006

Health effects in fish of long-term exposure to effluents from wastewater treatment works.

Concern has been raised in recent years that exposure to wastewater treatment effluents containing estrogenic chemicals can disrupt the endocrine functioning of riverine fish and cause permanent alterations in the structure and function of the reproductive system. Reproductive disorders may not necessarily arise as a result of estrogenic effects alone, and there is a need for a better understanding of the relative importance of endocrine disruption in relation to other forms of toxicity. Here, the integrated health effects of long-term effluent exposure are reported (reproductive, endocrine, immune, genotoxic, nephrotoxic) . Early life-stage roach, Rutilus rutilus, were exposed for 300 days to treated wastewater effluent at concentrations of 0, 15.2, 34.8, and 78.7% (with dechlorinated tap water as diluent). Concentrations of treated effluents that induced feminization of male roach, measured as vitellogenin induction and histological alteration to gonads, also caused statistically significant alterations in kidney development (tubule diameter), modulated immune function (differential cell count, total number of thrombocytes), and caused genotoxic damage (micronucleus induction and single-strand breaks in gill and blood cells). Genotoxic and immunotoxic effects occurred at concentrations of wastewater effluent lower than those required to induce recognizable changes in the structure and function of the reproductive endocrine system. These findings emphasize the need for multiple biological end points in tests that assess the potential health effects of wastewater effluents. They also suggest that for some effluents, genotoxic and immune end points may be more sensitive than estrogenic (endocrine-mediated) end points as indicators of exposure in fish.

Animals↗
PubMed1986

[Continuing eco-pathological survey: 11. Development of pathological frequency in dairy cow stock as a function of the stage of lactation].

The study of disease distribution observed during lactation shows that three patterns of pathology may be described: diseases for which critical period is post-partum time: we observed during the first month of lactation 32.2% of cases of clinical mastitis, 43.9% of cases of metritis, 37.9% of digestive disorders, 59.6% of appetite troubles, 23.1% of treat lesions and 52.9% of udder edema. The monthly curve squares with asymptotic function. foot disorders for which the high milk yield production period is the more sensible time (three first month of lactation). The monthly curve, near a linear decreasing, squares with a quadratic or square-root function. ovarian pathology for which frequencies depends more acute attention from breeders or clinicians to reproductive disorders than objective observation of ovarian dysfunction.

Animals↗
PubMed2005

Kisspeptin and its receptor: new gatekeepers of puberty.

The recent finding that the hormone kisspeptin plays a pivotal role in the onset of puberty is one of the biggest discoveries in human reproductive biology in 30 years. Mutations in the receptor for kisspeptin cause humans and mice to fail to reach puberty and to be sterile. It is the first time since the identification of gonadotrophin-releasing hormone that a single gene is found to have such a dramatic effect on reproduction. This discovery opens new possibilities in the treatment of reproductive disorders such as delayed or advanced puberty, infertility and sex hormone-dependent cancers.

Animals↗
PubMed2000

Wolbachia density and host fitness components in Muscidifurax uniraptor (Hymenoptera: pteromalidae).

Intracellular bacteria of the genus Wolbachia are found in a variety of arthropod hosts, where they cause various reproductive disorders. Attempts to study the fitness advantages and disadvantages of carrying these symbionts have yielded contradicting results. Using various doses of the antibiotic rifampicin, we were able to manipulate the density of Wolbachia in the uniparental parasitoid Muscidifurax uniraptor (Hymenoptera: Pteromalidae). The effect of different titers of the symbiont on the fecundity, reproductive rate, longevity, survival rate, and sex ratio of the host was measured. The data gathered show that following antibiotic treatments, the percentage of males rises at low doses of rifampicin and then drops again. The total sex ratio of offspring produced by treated mothers was positively correlated with the numbers of Wolbachia found in eggs laid by these females. No significant effects were detected with regard to the other studied fitness components. It is concluded that in M. uniraptor, Wolbachia are not posing any burden on the life history trait studied.

Animals↗
PubMed1991

Neuroendocrine control of human reproduction in the male.

The traditional difficulty in studying the neuroendocrine control of reproduction in the human male has been the inability to tease out the hypothalamic from the pituitary component of this neuroendocrine system. The use of multiple models, each with its own strength and weakness, represents an overlapping approach that has permitted further insights to be gained into the hypothalamic control of the neuroendocrine regulation of gonadotropin secretion in the human. Such an insight is an important prerequisite to the understanding of the pathophysiology of various disease states, the unraveling of a control of FSH secretion by GnRH vs other modulators, and the subsequent design of rational therapies for male reproductive disorders.

Follicle Stimulating Hormone↗
PubMed1997

Advances in understanding gonadotrophin-releasing hormone receptor structure and ligand interactions.

Gonadotrophin-releasing hormone (GnRH) is the central regulator of the reproductive system and its analogues are used widely in the treatment of diverse diseases. The GnRH receptor is a member of the large family of G-protein-coupled receptors (GPCRs) which have seven transmembrane domains. Knowledge of these receptors has assisted the development of molecular models of the GnRH receptor that allow prediction of its three-dimensional configuration and the way GnRH binds and activates its receptor. Comparison with other GPCRs led to the discovery that Lys121, in the third transmembrane domain, has a role in agonist binding. The history of GnRH structure-activity studies has allowed the identification of an acidic residue in the third extracellular loop of the receptor that is required for binding of mammalian GnRH, while synthetic GnRH analogues have showed that Asn102, in the second extracellular loop, may interact with the carboxy-terminus of GnRH. These residues can now be incorporated into the receptor models that are being used to design orally active non-peptide GnRH analogues for contraception and treatment of a variety of reproductive disorders.

Amino Acid Sequence↗
PubMed2006

How do environmental estrogen disruptors induce precocious puberty?

Puberty is regulated by the endocrine system. Disruption of that system by exposure to environmental hormone-mimicking substances (i.e. endocrine disruptors) may, therefore, affect this development profoundly. There has been a great secular trend in the earlier timing of puberty such as both puberty onset and menarche age. This is apparently caused by environmental factors such as improved socioeconomic status, better healthcare and improved nutrition. However, part of the phenomenon could be associated with exposure to endocrine disruptors that have intrinsic estrogen activity or increase endogenous sex hormone levels. These estrogen pollutants tend to degrade slowly in the environment, to bioaccumulate in the food chain and to have long half-lives in humans. Because most of environmental chemicals, called estrogen disruptors or xenoestrogens, are toxic and estrogen/antiandrogen active, they can disregulate hypothalamic-pituitary-gonadal axis potentially inducing reproductive disorders. There are several case reports of accidental exposure to estrogenic compounds in cosmetic products, food and pharmaceuticals. The outbreak of epidemics of premature thelarche in some geographical areas has also been suggested to be linked to exposure to estrogen disrupters such as dioxins, furans and organohalogens. We review data on adverse health and reproductive outcomes have been attributed to estrogen disruptors in laboratory animals and in wildlife as well as in humans, specially focusing on the puberty timing.

Age Factors↗
PubMed1992

Pharmacologic considerations in the management of peripartum conditions in the cow.

As is true with the use of drugs in veterinary medicine in general, there are many controversial issues in the management of peripartum conditions in the cow. For example, the use of PG versus antibacterial drugs in the management of postpartum uterine infections has advocates for the use of either approach. Intrauterine versus systemic administration of antibacterial drugs for the prophylaxis or treatment of postpartum metritis is another area of debate. Clearly, more research is needed in this area. Equally clearly, however, the research results that are available are being disregarded on a daily basis. In considering this discussion of the use of drugs in the peripartum period, one is struck by the frequency that optimum drug therapy of a condition relies on the extralabel use of nonapproved preparations. What guidelines are available to the practitioner in this regard? One example is lack of availability of appropriate dosage regimens or withdrawal times for food derived from treated animals. Unfortunately, pharmacokinetic and residue studies that would aid in establishing guidelines generally are not available and, in most instances, are not forthcoming. Extrapolation of data from other species to the ruminant or extrapolation of information from one drug to a related compound (such as prediction of residue and withdrawal data from an approved aminoglycoside, dihydrostreptomycin, to another unapproved drug, gentamicin) is fraught with difficulties. The need for research in this area is obvious, and lack of such information is one of the major dilemmas in trying to establish rational drug therapy in the food-producing animal. Recent developments in drug therapy have led to innovative approaches for the management of peripartum and other diseases in cattle. The use of PG in the treatment of reproductive disorders, so commonplace and widely accepted in contemporary veterinary practice, is a relatively recent approach that continues to be refined with the development of new, more potent, more specific PG analogs. What will be the role of ceftiofur, a potent, third-generation cephalosporin that currently is approved only for the treatment of respiratory infections in cattle, in the management of reproductive tract infections? The fluoroquinolones, which represent a novel approach to the control of infectious diseases, are being increasingly used in veterinary and human medicine, and one may predict that these powerful antimicrobial drugs will find application in bovine practice, including for the treatment of peripartum infections. Pharmacologic manipulation of immune and defense mechanisms also is an approach with some promise.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1996

Male reproductive health and environmental xenoestrogens.

Male reproductive health has deteriorated in many countries during the last few decades. In the 1990s, declining semen quality has been reported from Belgium, Denmark, France, and Great Britain. The incidence of testicular cancer has increased during the same time incidences of hypospadias and cryptorchidism also appear to be increasing. Similar reproductive problems occur in many wildlife species. There are marked geographic differences in the prevalence of male reproductive disorders. While the reasons for these differences are currently unknown, both clinical and laboratory research suggest that the adverse changes may be inter-related and have a common origin in fetal life or childhood. Exposure of the male fetus to supranormal levels of estrogens, such as diethlylstilbestrol, can result in the above-mentioned reproductive defects. The growing number of reports demonstrating that common environmental contaminants and natural factors possess estrogenic activity presents the working hypothesis that the adverse trends in male reproductive health may be, at least in part, associated with exposure to estrogenic or other hormonally active (e.g., antiandrogenic) environmental chemicals during fetal and childhood development. An extensive research program is needed to understand the extent of the problem, its underlying etiology, and the development of a strategy for prevention and intervention.

Animals↗
PubMed2004

Adverse effects of environmental toxicants, octylphenol and bisphenol A, on male reproductive functions in pubertal rats.

It has been proposed that a global decline in sperm counts, semen quality, and several male reproductive disorders are associated with exposure to environmental chemicals. Thus, the present study examined the effects of two estrogenic chemicals, octylphenol (OP) and bisphenol A (BPA), on epididymal sperm counts and sperm motility, luteinizing hormone (LH)-releasing hormone (LHRH)-stimulated plasma LH and steroid hormones, insulin-like growth factor I (IGF-I), and accessory reproductive organs in pubertal male Wistar rats. Fifty-day-old rats in the OP group (n=11) and BPA group (n=11) received daily sc injections of the respective chemical at a dose of 3 mg/kg bw dissolved in 0.2 mL DMSO. Rats in the control group (DMSO group; n=10) received 0.2 mL DMSO alone. After 2 wk of treatment, a jugular blood sample was taken, and, on the next day, a second blood sample was taken 1 h after an sc injection of LHRH (250 ng). After 5 wk of treatment, rats were deeply anesthetized and heart blood was collected. Epididymal sperm motility and sperm head counts were determined. LHRH increased plasma LH to higher levels in all groups, but the increases were significant (p<0.01) in the BPA and OP groups. However, despite higher LH levels after LHRH injection, the incremental responses of testosterone and pro-gesterone in the OP and BPA groups were small compared to those in the DMSO group, which showed a small LH response. After 5 wk of treatment, plasma testosterone levels were significantly (p<0.01) reduced in the OP and BPA groups and this was accompanied by reduced (p<0.05) epididymal sperm counts. However, the chemical-treated groups had high basal progesterone levels. No significant effects of chemicals on sperm motility parameters were noted. The chemical-induced increases (p<0.05) of the weight of ventral prostate gland were coincided with elevated plasma IGF-I levels in the BPA (p<0.05) and OP (p<0.01) groups. The present results demonstrated that OP and BPA can reduce sperm counts resulting from lowered plasma testosterone in male rats just after puberty. The enlarged ventral prostate gland may possibly be associated with increased plasma IGF-I, raising the possibility of a link between these chemicals and prostate diseases because IGF-I has been implicated in the pathogenesis of human prostate cancers.

Animals↗