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PubMed2005

Metabolic variables and plasma leptin concentrations in dairy cows exhibiting reproductive cycle abnormalities identified through milk progesterone monitoring during the post partum period.

We have used milk progesterone analysis to monitor reproductive function in lactating dairy cows and have then related this reproductive function to a variety of metabolic variables. Monitoring of cows (n = 41) during the period of onset of luteal function (first milk progesterone reading>5 ng/ml) revealed that delayed onset was associated with increased milk yield and greater loss of body weight and body condition but was not related to plasma metabolite or leptin concentrations. Further monitoring of reproductive function in these 41 cows and an additional 33 cows (total n = 74) during the mating period (from weeks 6 to 14 post partum) identified reproductive cycle abnormalities in 29 (39.2% of animals). The occurrence of cycle abnormalities was associated with increased milk yield (P < 0.05), elevated plasma beta hydroxybutyrate (P < 0.05) and reduced plasma leptin (P < 0.01) concentrations as well as a lower (P < 0.05) rate of gain of body weight and condition score but was not associated with plasma urea or glucose concentrations. Furthermore, cows exhibiting cycle abnormalities had a longer (P < 0.01) interval to first service and a smaller percentage had conceived by 100 days post partum (34.5% versus 66.7%; P < 0.01). These results provide further evidence that impaired reproductive function during the post partum period in dairy cows is caused by a poor energy status and not elevated urea concentrations. Reduced plasma leptin concentrations in animals suffering reproductive dysfunction further supports this view.

3-Hydroxybutyric Acid↗

PubMed2005

GnRH in non-hypothalamic reproductive tissues.

Gonadotropin releasing hormone (GnRH) is a hypothalamic neuronal secretory decapeptide that plays a pivotal role in mammalian reproduction. GnRH and its analogues are used extensively in the treatment of hormone dependent diseases and assisted reproductive technology. Fourteen structural variants and three different forms of GnRH, named as hypothalamic GnRH or GnRH-I, mid brain GnRH or GnRH-II and GnRH-III across various species of protochordates and vertebrates have been recognised. The hormone acts by binding to cell surface transmembrane G protein coupled receptors (GPCRs) and activates Gq/11 subfamily of G proteins. Although hypothalamus and pituitary are the principal source and target sites for GnRH, several reports have recently suggested extra-hypothalamic GnRH and GnRH receptors in various reproductive tissues such as ovaries, placenta, endometrium, oviducts, testes, prostrate, and mammary glands. GnRH-II appears to be predominantly expressed in extra pituitary reproductive tissues where it produces its effect by PLC, PKA2, PLD, and AC cell signalling pathways. In these tissues, GnRH is considered to act by autocrine or paracrine manner and regulate ovarian steroidogenesis by having stimulatory as well as inhibitory effect on the production of steroid hormones and apoptosis in ovarian follicle and corpus luteum. In male gonads, GnRH has been shown to cause a direct stimulatory effect on basal steroidogenesis and an inhibitory effect on gonadotropin-stimulated androgen biosynthesis. Recent studies have shown that GnRH is more abundantly present in ovarian, endometrial and prostrate carcinomas. The presence of type-II GnRH receptors in reproductive tissues (e.g. gonads, prostrate, endometrium, oviduct, placenta, and mammary glands) suggests existence of distinct role(s) for type-II GnRH molecule in these tissues. The existence of different GnRH forms indicates the presence of distinctive cognate receptors types in vertebrates and is a productive area of research and may contribute to the development of new generation of GnRH analogues with highly selective and controlled action on different reproductive tissues and the target-specific GnRH analogues could be developed.

Animals↗

PubMed2004

Characterization of responses to the antiandrogen flutamide in a short-term reproduction assay with the fathead minnow.

A short-term reproduction assay with the fathead minnow (Pimephales promelas) has been developed to detect chemicals with the potential to disrupt reproductive endocrine function controlled by estrogen- and androgen-mediated pathways. The objective of this study was to use the assay to characterize responses of fathead minnow reproductive endocrinology and physiology to the mammalian antiandrogen, flutamide. Male and female fish were exposed to nominal (target) concentrations of 50 and 500 microg flutamide/l for 21-days, following which plasma steroid and vitellogenin concentrations were determined and gonadal morphology assessed. Fecundity of the fish was significantly reduced by exposure to a measured test concentration of 651 microg flutamide/l. In addition, embryo hatch was significantly reduced at this concentration. Qualitative histological assessment of ovaries from females exposed to flutamide indicated a decrease in mature oocytes and an increase in atretic follicles. Testes of males exposed to flutamide exhibited spermatocyte degeneration and necrosis. Concentration-dependent increases in plasma testosterone and vitellogenin concentrations were observed in the females. Flutamide also altered reproductive endocrinology of male fathead minnows. Males exposed to 651 microg flutamide/l exhibited elevated concentrations of beta-estradiol and vitellogenin. In summary, the results of this study with the fathead minnow demonstrate that flutamide affects reproductive endocrine function in fish and that the type of hormonal pattern and histopathology effects observed are consistent with an antiandrogenic mode-of-action. Consequently, our findings suggest that the 21-day reproduction assay utilizing fathead minnows is a sensitive short-term screening method for the detection of endocrine-disrupting chemicals, including antiandrogens.

Androgen Antagonists↗

PubMed2006

Reproductive aging in Japanese quail, Coturnix japonica is associated with changes in central opioid receptors.

Quantitative in vitro autoradiography was used to measure specific mu and delta opioid receptor densities in regions of the Japanese quail, Coturnix japonica, brain that regulates reproductive endocrine and behavioral responses to determine the possible involvement of the opioid system in reproductive decline seen during aging. Densities were measured in selected brain regions of young sexually active (YAM), young photoregressed (YPM), old reproductively senescent (OIM) male, young active (YF), and old senescent female (OF) Japanese quail. Medial and lateral septum (SM, SL), medial preoptic area (POM), and n. intercollicularis (ICo) were of particular interest for reproductive responses. Similar to previous observations, mu and delta opioid receptors showed differential distributions in the areas measured. Some age-related changes were observed, with lower SM mu receptor densities in aged males (OIM) than females or young males (YAM). Densities of mu receptors in the POM and in other areas examined did not vary with sex or age. Similarly, OIM males had lower densities of delta receptors in the SM than young males (YAM and YPM); POM delta receptor densities were also low in OIM males compared to the YPM males, and YAM males were intermediate. Interestingly, photoregressed males (YPM) had higher SL delta receptor densities than any other group. Thus there were age-related differences detected in mu receptor densities among groups in the SM of OIM relative to other groups; and the mu and delta receptor densities did not differ in females with brain region. Additionally for delta receptors specifically, YF and OF did not differ from OIM for any brain region and similarly had lower densities of delta receptors compared to YAM males. These data provide support for regional differences in opioid receptor distribution and for age- and sex-related differences in delta opioid receptor densities. The direction of change presents an interesting dichotomy in that, compared to young active males, delta opioid receptor densities increased with loss of reproductive function in the YPM, whereas receptor densities decreased in the OIM. Plasma androgen levels were relatively low in both these groups compared to the young active males. This observation suggests that there is an age-related loss in the ability of this receptor system to respond to circulating and centrally produced steroid hormones in the POM and in some septal regions, compared to young animals that are responding to environmental cues. Furthermore, these data support an active role of the opioid peptide system in the inhibition of the reproductive axis in photoregression.

Aging↗

PubMed2005

Impact of endocrine disrupting chemicals on reproduction in Japanese quail.

Many environmental contaminants can interact with the endocrine system, thereby potentially disrupting the reproductive fitness of individuals. In avian species, the egg-yolk is a major route for excretion of lipophilic compounds by the adult female bird and embryos are exposed to contaminants that have been deposited in the eggs. The reproductive and neuroendocrine system of Japanese quail undergoes sexual differentiation during embryo development. The phenotypic sex, including sex-specific adult behavior, is hormonally imprinted already before hatching. The sexual differentiation of the brain in quail is sensitive to estrogens and the presence of estrogen results in a female phenotype. The relatively low concentration of estrogens in male embryos, on the other hand, results in a male behavioral phenotype. The behavior of male quail can be demasculinized by estrogen exposure during the period of sexual differentiation, and estrogen-exposed males are not able to display a male-typical behavior as adults. Also, differentiation of the reproductive organs is sensitive to hormones during embryogenesis, and an excess of estrogens can for instance induce persistent morphological changes in the reproductive organs of females. Our research has focused on effects in adult birds after embryonic estrogen exposure. We have studied sexual behavior and other reproductive variables in adult quail after in ovo injection of known and suspected estrogenic compounds. Synthetic estrogens and insecticides, such as o,p'-DDT altered the development of the neural system and resulted in demasculinization of male quail. In females, o,p'-DDT caused morphological changes of the oviduct and egg laying was reduced. Our studies suggest that the neural system and the female reproductive system of avian embryos are very sensitive to the effects of chemicals with estrogenic activity.

Animals↗

PubMed2006

Gender-based differences in endocrine and reproductive toxicity.

Basic differences in male versus female reproductive physiology lead to differentials in their respective susceptibilities to chemical insult as evidenced by a variety of observations. As individuals undergo maturation from prenatal sex differentiation through pubertal development, these susceptibilities become evident in each gender. Gender bias occurs in human populations for birth defects and for the acceleration of the onset of puberty. Data on gender bias in fetal origins of adult disease are more complex. Useful for understanding reproductive and developmental effects in animals are a range of standard methodological procedures including the multigeneration testing protocol and the National Toxicology Program (NTP) Reproductive Assessment by Continuous Breeding (RACB). Examples of gender-based differences seen in reproductive toxicology studies on animals include teratogenic effects, reproductive effects in adult males and females, and effects on pubertal development. It is clear that gender biases exist in the reproductive and developmental toxicity, and the biological bases for these differences need to be explored.

Age Factors↗

PubMed2006

[Products toxic to reproduction used in the occupational environment: Definition, risk assessment, classification].

European regulations (transcribed into French law) aimed at protecting employees from chemicals toxic to reproduction enable classification and labelling of such substances, if they are liable to cause an alteration of male or female reproductive functions or capacity, or to induce non-hereditary harmful effects on their offspring. Three categories can be used to classify these substances in two areas, namely their impairment of fertility and their effects on development. This classification is rarely based on epidemiological study results, but most often on those of experimental toxicological studies conducted by substance manufacturers. These reproduction toxicological studies are only compulsory above a certain tonnage placed on the market. The high level of this tonnage means that these tests are effectively only conducted on rare occasions. It is reckoned that there is no reproduction experimental data for over 95% of substances newly placed on the market. These products therefore appear to be reproduction non-toxic only because they have not been tested. This is a major fault in the current labelling system, which does not allow non-toxic products to be differentiated from non-tested products. The future EU regulatory framework for Registration, Evaluation and Authorisation of CHemicals (REACH) will only slightly enhance information in this area. It can be estimated that over 80% of chemical products will not be exhaustively tested for reproduction and nearly 75% will not be tested to any degree.

Europe↗

PubMed2004

Variation in cuticular hydrocarbon signatures, hormonal correlates and establishment of reproductive dominance in a polistine wasp.

In many social insects the relationship between reproductive dominance and physiological correlates is poorly understood. Recent evidence now strongly suggests that cuticular hydrocarbons are important in reproductive differentiation in these societies where they are used as signals of ovarian activity in reproductive females. In this study we investigated the relationship between reproductive dominance, size of the corpora allata (CA, producer of Juvenile Hormone, JH) and the proportions of cuticular hydrocarbons present on the cuticle in overwintering foundresses and both associative (polygynous) and solitary (monogynous) pre-emergence colonies of the social wasp Polistes dominulus. Size of the CA was positively correlated with ovarian development in polygynous colonies. In contrast, solitary foundresses possessed significantly smaller CAs than dominant foundresses from polygynous nests, yet ovarian activity was similar for both female types. CA size variation was associated with variation in cuticular hydrocarbon proportions. Overwintering, solitary, dominant and subordinate (from associative nests) females all possessed distinctive cuticular chemical profiles revealed by multivariate discriminant analyses. Our data indicate that the social environment strongly affects reproductive physiology in this wasp, and we discuss the role of cuticular hydrocarbons in reproductive signaling in P. dominulus and other social insects.

Animals↗

PubMed2005

Effects of adult-derived carbohydrates, amino acids and micronutrients on female reproduction in a fruit-feeding butterfly.

It is generally believed that butterflies (and other holometabolous insects) rely primarily on reserves accumulated during the larval stage for reproduction, whereas the carbohydrate-rich adult diet is thought to mainly cover energy requirements. In at least some species though, realization of the full reproductive potential is extensively affected by post-eclosion nutrition. While the importance of carbohydrates is fairly well understood, the role of adult-derived amino acids and micronutrients is controversial and largely unknown, respectively. We here focus on the effects of different adult diets on female reproduction in the tropical, fruit-feeding butterfly Bicyclus anynana (Nymphalidae). Carbohydrates were the most important adult-derived nutrients affecting reproduction. Adding amino acids, vitamins or minerals to sucrose-based solutions did not yield a reproductive output equivalent to that of fruit-fed females, which showed the highest performance throughout. This suggests that either not yet identified compounds of fruit substantially contribute to reproduction, or that resource congruence (the use of nutrient types in a specified ratio) rather than any specific nutrient component is of key importance. Apart from adult income, realized fecundity depended on egg size and longevity, with the former dominating when dietary quality was low, but the latter when quality was high. Thus, the egg size-number trade-off seems to be affected by female nutrition.

Amino Acids↗

PubMed2005

Cost of reproduction in Callosobruchus maculatus: effects of mating on male longevity and the effect of male mating status on female longevity.

One of the most studied life-history trade-offs is that resulting from the cost of reproduction: a trade-off arises when reproduction diverts limited resources from other life-history traits. We examine the cost of reproduction in male, and the effect of male mating status on female Callosobruchus maculatus seed beetles. Cost of reproduction for male C. maculatus was manifested as reduced longevity. There was also a positive relationship between male body size and male longevity. Females mated to males that had already copulated twice did not live as long as females mated to males that had copulated once or not at all. The third copulation of males also lasted longer than the two previous ones. We conclude that even though the cost of reproduction for males has been studied much less than that in females, there is growing evidence that male reproductive effort is more complex than has traditionally been thought.

Analysis of Variance↗

PubMed2006

Mutations in fibroblast growth factor receptor 1 cause Kallmann syndrome with a wide spectrum of reproductive phenotypes.

BACKGROUND: Kallmann's syndrome (KS) is a clinically and genetically heterogeneous disorder consisting of idiopathic hypogonadotropic hypogonadism (IHH) and anosmia. Mutations in KAL1 causing the X-linked form of KS have been identified in 10% of all KS patients and consistently result in a severe reproductive phenotype. KAL1 gene encodes for anosmin-1, a key protein involved in olfactory and GnRH neuronal migration through a putative interaction with FGFR1. Heterozygous mutations in the FGFR1 gene accompanied by a high frequency of cleft palate and other facial dysmorphisms were recently identified in 8% of a large KS cohort, yet the reproductive phenotype of KS patients harboring FGFR1 mutations has not been described. RESULTS: One hundred and fifty probands with KS (130 males and 20 females) were studied to determine the frequency and distribution of FGFR1 mutations and their detailed reproductive phenotypes. Fifteen heterozygous mutations in unrelated probands were identified. Twelve missense mutations (p.R78C, p.V102I, p.D224H, p.G237D, p.R254Q, p.V273M, p.E274G, p.Y339C, p.S346C, p.I538V, p.G703S and p.G703R) were distributed among the first, second and third immunoglobulin-like domains (D1-D3), as well as the tyrosine kinase domain (TKD). The mutations Y339C and S346C are located in exon 8B and code for the isoform FGFR1c. Additionally, two nonsense mutations (p.T585X and p.R622X) were documented in the TKD of the protein. A wide spectrum of reproductive function was observed among KS probands including: (1) a severe phenotype demonstrated by microphallus, cryptorchidism, no pubertal development, undetectable serum gonadotropins and low serum testosterone (T) and inhibin B; (2) partial pubertal development; (3) the fertile eunuch variant of IHH with normal testicular size and active spermatogenesis with a reversal of HH after T therapy. In addition, we found an even wider spectrum of reproductive function within pedigrees carrying an FGFR1 mutation ranging from IHH to delayed puberty to normal reproductive function (anosmia only or asymptomatic carriers). These observations strongly suggest a role for other genes that modify the phenotype of FGFR1 mutations. CONCLUSION: KS patients and family members carrying an FGFR1 mutation present a broad spectrum of pubertal development in contrast to the almost uniform severe clinical phenotype described in KS subjects with a KAL1 mutation. Additionally, this report implicates the isoform FGFR1c in the pathogenesis of KS.

Adolescent↗

PubMed2006

Novel signals for the integration of energy balance and reproduction.

Although the close link between body weight and fertility has been known for eons, only recently have the peripheral signals and neuroendocrine networks responsible for such a phenomenon begun to be identified. A key event in this field was the cloning of the adipocyte-derived hormone leptin, which has been demonstrated as a pivotal regulator for the integration of energy homeostasis and reproduction. In addition, other metabolic hormones, such as insulin, contribute to this physiological integration. Moreover, compelling experimental evidence implicates hormonal products of the gastrointestinal tract as adjuncts in the complex coordination and regulation of body weight and reproduction. Here, we review recent studies evaluating the reproductive effects and sites of action of ghrelin and PYY3-36, two hormonal signals of gastrointestinal origin involved in the control food intake and energy balance. In addition, we summarize the potential contribution of kisspeptin, the recently characterized gatekeeper of the GnRH system encoded by Kiss1 gene, to integrating reproductive function and energy status. Evidence suggests that besides having direct gonadal effects, ghrelin may participate in the regulation of gonadotropin secretion and it may influence the timing of puberty. Likewise, PYY3-36 modulates GnRH and gonadotropin release. In addition, the hypothalamic KiSS-1 system is sensitive to nutritional status, and its diminished expression during states of negative energy balance might contribute to the suppression of reproductive function in such conditions. We propose that the peripheral hormones, ghrelin and PYY3-36, and the central neuropeptide, kisspeptin, are 'novel' players in the neuroendocrine networks that integrate energy balance and reproduction.

Animals↗

PubMed2004

Clonal reproduction and linkage disequilibrium in diploids: a simulation study.

Estimating the rate of clonal reproduction in natural population of diploid organisms is recognised as being problematic and even the detection of strictly clonal populations is often controversial. One well-acknowledged signature of clonal reproduction is the generation of non-random associations between loci. Linkage disequilibrium (LD) is thus often used for estimating the amount of clonal reproduction. Here we explore with computer simulations the effect of the rate of clonal reproduction on LD estimates obtained from different estimators within a comprehensive parameter range. None of the LD estimators studied is able to accurately measure the proportion of clonal (or sexual) reproduction on its own, due to strong bias, incoherent behaviour, or huge variances. The joint use of several statistics is thus recommended for the estimation rates of clonal reproduction in natural populations. We hope that our work will provide useful tools for the study of clonal diploids, many of which can only be studied with molecular markers, as it is the case for medically important parasites.

Clone Cells↗

PubMed2004

Men's influences on women's reproductive health: medical anthropological perspectives.

Reproductive health has emerged as an organizational framework that incorporates men into maternal and child health (MCH) programs. For several decades, medical anthropologists have conducted reproductive health research that explores male partners' effects on women's health and the health of children. This article summarizes exemplary research in this area, showing how ethnographic studies by medical anthropologists contribute new insights to the growing public health and demographic literature on men and reproductive health. The first half of the article begins by exploring reproductive rights, examining the concept from an anthropological perspective. As part of this discussion, the question of equality versus equity is addressed, introducing anthropological perspectives on ways to incorporate men fairly into reproductive health programs and policies. The second half of the article then turns to a number of salient examples of men's relevance in the areas of contraception, abortion, pregnancy and childbirth, infertility, and fetal harm. Medical anthropological research--as well as prominent gaps in that research--is highlighted. The article concludes with thoughts on future areas of anthropological research that may improve understandings of men's influences on women's reproductive health.

Anthropology, Cultural↗

PubMed2005

Gelatinases and serine proteinase inhibitors of seminal plasma and the reproductive tract of turkey (Meleagris gallopavo).

This study examined proteolytic enzymes and serine proteinase inhibitors in turkey seminal plasma with relation to their distribution within the reproductive tract and to yellow semen syndrome (YSS). Proteases of blood plasma, extracts from the reproductive tract, and seminal plasma were analyzed by gelatin zymography. We found a clear regional distribution of proteolytic enzymes in the turkey reproductive tract. Each part was characterized by a unique profile of serine proteolytic enzymes of molecular weights ranging from 29 to 88 kDa. The ductus deferens was found to be a site of very intense proteolytic activity. Two metalloproteases of 58 and 66 kDa were detected in all parts of the reproductive tract and seminal plasma. Using electrophoretic methods for detection of anti-trypsin activity, we found three serine proteinase inhibitors in turkey seminal plasma. Two inhibitors were found in the testis and epididymis and a third in the ductus deferens and seminal plasma. Blood plasma was characterized by the presence of two metalloproteinases and one serine proteinase inhibitor (of low migration rate) that were also detected in the reproductive tract. Amidase and anti-trypsin activities (expressed per gram of protein) differed for yellow and white seminal plasma. We concluded that turkey seminal plasma contains metalloproteases, serine proteinases, and serine proteinase inhibitors. The metalloproteases and one proteinase inhibitor are related to blood proteinases but the other two inhibitors and serine proteinases seem to be unique for the reproductive tract.

Animals↗

PubMed2005

Fertility in South Australian commercial Merino flocks: relationships between reproductive traits and environmental cues.

High levels of reproductive loss have been reported in commercial Merino flocks (n=68) from the cereal/livestock and high rainfall zones in South Australia (Kleemann DO, Walker SK. Fertility in South Australian commercial Merino flocks: sources of reproductive wastage. Theriogenology 2005;63:2075-88). Relationships between reproductive traits (estrus, ovulation, fertility, fecundity, lamb survival) and environmental end points (liveweight, condition score, temperature at mating, chill index at lambing) are reported in this paper. They were analysed within season of mating (October to December; January to March) and age of ewe (maiden as 1.5-year-old, mature as older). Incidence of estrus was positively related (P<0.05) to condition score in the October to November interval. Return rate to service was positively (P<0.05) influenced and fertility was negatively (P<0.05) influenced by the number of days ambient temperatures were > or =32.0 degrees C during mating, indicating that high ambient temperatures may reduce embryo survival. Liveweight and, to a lesser extent, condition score, accounted for significant proportions of variation associated with ovulation rate (39.3 and 12.7%, respectively). Ovulations per 100 ewes increased by 1.8 per kg increase in liveweight over all flocks. Ovulatory response to liveweight increased (P<0.01) from the October to December to the January to March period of mating (1.5 versus 3.4 ovulations per kg, respectively). Overall, a flock's fertility and fecundity increased by 0.27 and 1.42% per kg increase in liveweight, respectively. Reproductive wastage from partial failure of multiple ovulations (PFMO) was positively related to liveweight (P<0.01) and ovulation rate (P<0.001). Survival of single lambs was positively and curvilinearly related to maternal liveweight and condition score measured in late pregnancy (P<0.05). Linear relationship of these variables for twin lamb survival was significant for condition score only. Single and twin lamb survival were also positively related to liveweight and condition score at mating (P<0.05). We concluded that nutritional cues have a major impact on reproductive traits in commercial Merino flocks in South Australia; it sets the potential number of lambs (ovulation rate) and influences survival of lambs as early as at mating. Indications are that high ambient temperatures may influence embryo survival. It is recommended that future research efforts focus on: (a) prenatal nutritional influences on the physiology of mother-offspring behaviours at birth; and (b) possible peri-conceptional dietary factors controlling embryo loss resulting from partial failure of twin ovulations, to improve reproductive efficiency in the Merino.

Animals↗

PubMed2006

Effects of a GnRH cytotoxin on reproductive function in peripubertal male dogs.

Methods for long-term or permanent disruption of reproductive function via nonsurgical techniques are needed for a variety of species, including companion animals. In a previous study, we demonstrated the ability of a cytotoxin (pokeweed antiviral protein-PAP) conjugated to d-Lys(6)-GnRH, to disrupt reproductive function in adult male dogs. The objective of the present study was to examine the ability of a d-Lys(6)-GnRH-PAP conjugate to disrupt reproductive function in peripubertal male dogs. Peripubertal male dogs (n=15; approximately 16-32 weeks old) were treated with d-Lys(6)-GnRH-PAP as follows: dogs (n=7; Group I) received GnRH-PAP (0.1 mg/kg SQ) with a second treatment (0.25 mg/kg) 20 weeks later. An additional group (n=3; Group II) of peripubertal dogs was treated with GnRH-PAP (0.25 mg/kg) twice (20 weeks apart). Control dogs (n=5) received d-Lys(6)-GnRH analog (0.0045 mg/kg SQ) without PAP. Efficacy was assessed by monitoring testis size, serum concentrations of testosterone and LH, as well as LH release subsequent to a GnRH (5 microg/kg) stimulus. Dogs in Group I (n=5) that did not respond to the initial two treatments were given a third GnRH-PAP injection (0.25 mg/kg), 12 months after the initial treatment. The initial GnRH-PAP treatment in peripubertal male dogs did not affect testis growth, LH release or serum testosterone concentrations; however, administration of a higher dose of GnRH-PAP after puberty resulted in a marked and rapid decline in testis size, serum testosterone concentrations and LH responsiveness to GnRH stimulation in 9 of 10 dogs. Suppression of reproductive function was maintained in treated dogs for 18-50 weeks; four dogs had suppression of reproductive activity through the end of the study. In conclusion, GnRH-PAP given after puberty markedly suppressed reproductive activity. Due to variability in the response and duration of suppression after treatment with GnRH-PAP, more research is required to determine its efficacy for nonsurgical sterilization of the male dog.

Animals↗

PubMed2004

The reproductive toxicology of ammonium perfluorooctanoate (APFO) in the rat.

Ammonium perfluorooctanoate (APFO) is a surfactant used primarily as an aid in processing various fluoropolymers. Many toxicology and epidemiological studies have been conducted with APFO; however, no specific information regarding functional reproduction was previously available. Therefore, the potential reproductive toxicity of APFO across two generations of offspring was studied using current EPA OPPTS 870.3800 guidelines. Male and female Sprague-Dawley rats were dosed orally with 0, 1, 3, 10, or 30 mg/kg APFO. Parental (P) generation rats ( approximately 6 weeks old) were dosed at least 70 days prior to mating and until sacrificed (after mating for male rats; after weaning for female rats). F(1)-generation rats were dosed similarly, beginning at weaning. The F(2)-generation pups were maintained through 22 days of lactation. Reproductive parameters evaluated in P- and F(1)-generation rats included estrous cycling, sperm number and quality, mating, fertility, natural delivery, and litter viability and growth. Age at sexual maturation in F(1), anogenital distance in F(2), and presence of nipples (males) in F(2)-generation pups were also determined. Feed consumption, body-weight gain, selected organ-weights, gross pathology and appropriate histopathology were evaluated. Reproductive endpoints including mating, fertility, and natural delivery were not affected in either generation. P- and F(1)-generation male rats showed decreased body weight, and liver and kidney weight increases at all doses. The 30 mg/kg F(1)-generation pups had decreased birth weight. Viability was reduced in the 30 mg/kg F(1)-generation pups in apparent relationship to reduced body weight at birth and weaning; however, F(2)-generation pups at 30 mg/kg, although somewhat lighter, did not show a loss in viability. Preputial separation and vaginal opening were somewhat delayed at 30 mg/kg, but these rats went on to show normal reproductive performance. No-observed-adverse-effect-levels were >30 mg/kg for reproductive function of P- and F(1)-generation rats, 10 mg/kg for F(1)-generation pup mortality, birth weight, and sexual maturation, and less than 1mg/kg for male body-weight and organ-weight changes.

Animals↗