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An analysis of avian reproduction studies submitted for pesticide registration.

Avian reproduction studies are currently part of the regulatory ecotoxicology requirements for pesticides in many countries. In the study, 134 avian reproduction studies were reviewed to determine their ability to identify pesticides that have the potential to affect reproduction in wild birds. A clustering procedure was first used to assign measured variables to parental, developmental, or eggshell effects. This assignation was found to be identical in the two bird species tested. Nineteen of 69 pesticides tested were found to cause developmental effects at levels lower than those giving rise to detectable parental toxicity. At least some of these should not have been registered without some assurance that developmental effects would not occur in the wild. The analysis also found very little similarity in the effects of pesticides on the two bird species commonly used in avian reproduction tests. This casts serious doubts on the ability to extend the results of avian reproduction studies to any potentially affected bird species. Modifications to the avian reproduction test, based on results of the analysis conducted, are suggested. It is recommended that the avian reproduction study be recognized as a rough screening tool only and that efforts not be made to make it more realistic, e.g., such as through a reduced exposure period.

Animals↗

Reproductive toxicity of triethylene glycol and its diacetate and dimethyl ether derivatives in a continuous breeding protocol in Swiss CD-1 mice.

Triethylene glycol and two of its derivatives were evaluated for reproductive toxicity in a continuous breeding protocol with Swiss CD-1 mice. Triethylene glycol (TEG: 0, 0.3, 1.5, and 3%), triethylene glycol diacetate (TGD: 0, 0.75, 1.5, and 3%), and triethylene glycol dimethyl ether (TGDME: 0, 0.25, 0.5, and 1%) were administered in drinking water to breeding pairs (20 pairs per treatment group, 40 control pairs) during a 98-day cohabitation period. Reproductive function was assessed by the number of litters per pair, live pups per litter, proportion of pups born alive, and pup weight. There were no apparent effects on reproductive function in the animals receiving TEG or TGD at doses up to 3% in the drinking water (representing 6.78 or 5.45 g/kg, respectively). However, some developmental toxicity was demonstrated for both TEG and TGD. Continuous exposure of dams to 1.5 or 3% TEG significantly reduced live pup weight at birth compared to control and 0.3% TEG, while exposure to 3% TGD during lactation significantly (but reversibly) reduced pup body weights on Postnatal Days 14 and 21. In contrast, TGDME was toxic to the reproductive system as evidenced by decreases at the highest dose (1% TGDME; 1.47 g/kg) in the proportion of pairs that produced at least one litter, live pups per litter, and proportion of pups born alive, with dose-related trends seen in the latter two parameters. A crossover mating trial showed that TGDME was more toxic to the female than the male reproductive system. These data indicate that TGDME (1.47 g/kg) is a reproductive toxicant in Swiss mice while reproductive toxicity was not demonstrated in mice receiving TEG or TGD (at doses up to 6.78 or 5.45 g/kg, respectively).

Animals↗

Risk assessment policy for evaluating reproductive system toxicants and the impact of responses on sensitive populations.

Risk assessment policy for evaluating environmental chemicals for their potential to produce reproductive system failures is similar to policy for evaluating cancer-causing effects. The objective of reproductive system risk assessment is to expand on the test standards that primarily focus on fertility endpoints and birth defects by using mechanism-of-action studies and quantitative risk assessment methods. An understanding of the sensitivity of reproductive system insult between animal species and from animal models to man is critical to developing risk assessment policy and test standards. The reproductive process is complex and involves a number of maturation and sex cell development processes. Sensitivity to insult varies throughout this process, especially during, (1) the development of the conceptus, sperm and ova, (2) fertilization, (3) implantation, and (4) puberty. Reproductive failure has many causes and clinical effects. Risk assessment policy is directed toward reducing the uncertainty associated with the cause by providing a guide to understanding how dose, duration, and characteristics of the reproductive toxicant affect the reproductive process.

Animals↗

Review of reproductive and developmental toxicity of 1,3-butadiene.

Toxic doses of 1,3-butadiene (BD) have been reported to cause reproductive and/or developmental toxicity. Regardless of the strain used, mice were always affected by BD at lower doses than rats, an expected observation, based on well recognized differences in pharmacokinetic (PK) parameters in these two species. Because the mouse is particularly sensitive to BD in comparison with other laboratory species, and there are important functional and anatomical differences between humans and mice, the NOELs and LOELs identified for BD for various reproductive endpoints in mice may not be relevant to human reproductive risk. In mice, the LOELs for reproductive endpoints include developmental toxicity at 200 ppm, genotoxic effects at 500 ppm (mouse spot test), ovarian atrophy in females at 6.25 ppm (carcinogenicity study), reduced testicular weights at 200 ppm and testicular atrophy at 625 ppm BD in males (carcinogenicity studies), low incidences of abnormal sperm heads at 1000 and 5000 ppm BD (sperm head morphology study), small reversible increases in resorption at 1250/1300 ppm or 5000 ppm (dominant lethal studies), and other possible sequelae of genotoxicity resulting from exposure of male mice at 12.5 ppm BD and higher (dominant lethal study). When available, the much higher NOELs and LOELs of other species tested for the same endpoints should be considered. For example, maternal and developmental NOELs for BD in the rat were 200 and 1000 ppm, respectively, and 40 ppm in the mouse. Likewise, exposure of cohabited pairs of rats, guinea pigs and rabbits or of female dogs to BD concentrations as high as 6700 ppm for 8 months did not impair fertility or cause testicular or ovarian atrophy in these species. Thus, consideration of these remarkable species-dependent differences in toxicity is necessary. In addition, there are alternative scientific interpretations for some of the mouse studies and this review attempts to address these areas. For example, it may be incorrect to categorize results indicating weak in vivo genotoxic effects in male mice (sperm head morphology and dominant lethal studies) at 12.5 ppm BD and higher as reproductive effects because concentrations of BD as high as 5000 ppm did not affect mating, fertility or live litter sizes, even in this sensitive species. Similarly, it may be inappropriate to identify the ovary as a target organ for reproductive risk since the ovarian atrophy in mice was identified after completion of the normal reproductive life and after more than 15 months of exposure. Neither ovarian nor testicular atrophy occurred in Sprague-Dawley rats after exposure to BD concentrations as high as 8000 ppm for 105 (females) or 111 (males) weeks.

Animals↗

Correlations between serum corticosterone concentration and reproductive conditions in the white-footed mouse (Peromyscus leucopus noveboracensis).

1. Adrenal size and activity in reproductively inhibited young born into laboratory populations of the white-footed mouse were examined. Measurements were made of body weight, reproductive organ weight and adrenal weight. Serum corticosterone was measured by radioimmunoassay. 2. Data from reproductively inhibited animals were compared with corresponding values from reproductively capable animals of the same sex. The mean paired testis and seminal vesicle, or paired ovary and uterus, weights, were significantly reduced in reproductively inhibited animals of both sexes. The paired adrenal weights were not different in any comparison. 3. Reproductively inhibited males selected from laboratory populations had a mean corticosterone concentration that was significantly higher than the corresponding value for reproductively capable males. Females showed no significant difference in mean serum corticosterone concentrations. 4. The results are discussed in relation to earlier studies in two species of Peromyscus and the apparent paradox of elevated serum corticosterone in the absence of adrenal hypertrophy.

Adrenal Glands↗

Methods and concepts in detecting abnormal reproductive outcomes of paternal origin.

There is conclusive evidence that exposures of human males to ionizing radiation or certain chemicals can diminish sperm production and reduce fertility. Of approximately 100 chemical agents and mixtures that have been evaluated in men by semen analysis, about half (mostly drugs and a few occupational exposures) reduced sperm quantity and quality; several of these agents also affected the fertility of exposed men. It is now well recognized that the importance of the father in reproduction goes beyond fertilization. Abnormalities in paternal chromosomes (structural and numeric) have been found in various abnormal reproductive outcomes, including chromosomal abnormality syndromes among newborns. In rodent systems, exposure of males to mutagens before mating induces transmissible cytogenetic and genetic abnormalities as well as morphologic defects and cancer among offspring. Consistent with animal findings, there is growing epidemiologic evidence of associations between male exposures to exogenous agents and abnormal reproductive outcomes (fetal loss, birth defects, childhood cancer, etc.). However, no clear links have been established between exposure, mechanism of transmission, and abnormal reproductive outcomes. It is not known to what extent male-mediated birth defects and childhood cancer are due to genetic, epigenetic, or nongenetic causes. Viewed in a multigenerational context, the role of the father in abnormal reproductive outcomes is dependent on his exposure history and susceptibilities as well as those of his mate. Relevant exposures may occur any time between conception of the parents and production of their fertilizing gametes, including their development in utero, childhood, and adolescence. Efficient measurements (including biomarkers) of relevant exposure, early biologic effects, and susceptibility in human males are under development. An integrated approach is recommended for assessing male reproductive and genetic toxicity that utilizes biomarkers in (a) epidemiologic studies of exposed human populations, (b) risk characterization in sensitive laboratory species, and (c) in vivo and in vitro studies of the molecular mechanisms of action of toxicants. A special category of "bridging" biomarkers is needed for evaluating animal data for risk assessment and for discriminating among genetic, epigenetic, and nongenetic mechanisms of abnormal reproductive outcomes of paternal origin.

Adult↗

Organochlorine concentrations, reproductive physiology, and immune function in unique populations of freshwater Atlantic stingrays (Dasyatis sabina) from Florida's St. Johns River.

Within the past decade, reproductive and health disorders have been reported to occur in unique populations of Atlantic stingrays (Dasyatis sabina) inhabiting certain components of Florida's St. Johns River. Since these irregularities are consistent with the alleged effects of organochlorine (OC) contaminant exposure in other Florida wildlife, the goal of this study was to examine possible associations between OC concentrations and reproduction and/or immune function in stingrays from this river system. Liver concentrations of 30 OC pesticides/pesticide metabolites and total polychlorinated biphenyls (PCBs) were measured and compared in D. sabina collected from four central Florida lakes of the St. Johns River: Lake George, Lake Harney, Lake Jesup, and Lake Monroe. Reproductive biology, serum testosterone and 17beta-estradiol concentrations, and circulating white blood cell counts were examined and compared in stingrays from lakes that were determined to contain low (Lake George), intermediate (Lake Monroe), and high (Lake Jesup) levels of pesticide contamination, based on the results of liver OC assessments. Successful breeding occurred in Lake Jesup stingrays, indicating that the degree of OC accumulation in these animals is not high enough to cause reproductive impairment. However, elevated serum steroid concentrations and white blood cell counts were observed in Lake Jesup stingrays, suggesting that endocrine and immune function may be altered in these animals due to OC exposure and/or other, as yet unknown, ecological factors. Inconsistencies in the reproductive success of Lake Monroe stingrays were observed, confirming earlier reports of reproductive complications in this sub-population. Based on these findings, previous occurrences of reproductive failure in St. Johns River stingrays may be due to environmental factors other than OC exposure.

Animals↗

The relative sensitivity of growth and reproduction in the springtail, Folsomia candida, exposed to xenobiotics in the laboratory: an indicator of soil toxicity.

The Folsomia candida reproduction test [ISO, 1998. Soil quality--Inhibition of reproduction of Collembola (Folsomia candida) by soil pollutants. International Standard Organization Report 11267, 1998, Geneva] is used to evaluate the ecotoxicological risks of contaminants in soils. The aim of this study was to compare the sensitivity of growth and reproduction of F. candida to four xenobiotics: two metals (Cd, Al), one metalloid (As), and one organic compound (pentachlorophenol). We showed that reproduction is a slightly more sensitive parameter than growth: EC(20) for reproduction was 1.25 microg/g dry soil for arsenic, 56 microg/g for cadmium, 97.5 microg/g for aluminum, and 41.7 microg/g for pentachlorophenol. The corresponding EC(20) values for growth were 2.8, 65, 630, and 94.6 microg/g. Keeping in mind that a growth test needs fewer juveniles and less time than a reproduction test, we conclude that the two parameters are complementary and could be used for a better ecotoxicological evaluation of contaminants. However, the relative growth and reproduction sensitivities should be tested with more chemicals before growth could be considered as a good alternative for a faster sublethal test.

Aluminum↗

Reproductive aging results in a reconfigured ovarian antioxidant defense profile in rats.

OBJECTIVE: To test our hypothesis that reproductive aging changes the ovarian oxidative stress defense profile, in response to prostaglandin F2alpha (PGF2alpha) during corpus luteum regression, because how a cell or an organ handles reactive oxygen intermediates may be dependent on the biological age of the organism. DESIGN: Animal experimentation using rat model of corpus luteum regression. SETTING: University reproductive biology laboratory. ANIMAL(S): Control (26-day-old) and 8- to 9-month-old (reproductive aging) rats. INTERVENTION(S): Corpus luteum formation was induced in control and 8- to 9-month-old (reproductive aging) rats with pregnant mare serum gonadotropin followed by human chorionic gonadotropin. Regression was then initiated with PGF2alpha. MAIN OUTCOME MEASURE(S): Vitamin E, glutathione reductase, glutathione peroxidase, catalase, and thiobarbituric acid-reacting substances were measured. RESULT(S): Ovaries from reproductive aging rats, compared with the control (26-day-old) group, had elevated vitamin E levels at 0, 2, and 24 hours after PGF2alpha. At 2 and 24 hours after PGF2alpha, the aging ovaries had lower glutathione reductase levels. CONCLUSION(S): These data suggest that the reproductive aging ovary has a transformed oxidative stress defense profile and that this may account for some of the physiological changes found in reproductive aging.

Aging↗

[Assisted reproductive technologies after conservative management of borderline or invasive ovarian tumours].

OBJECTIVE: Ovulation induction, the usual resort of Assisted Reproductive Technologies (ART), has been suspected of carrying a responsibility in the genesis of ovarian tumours. For patients with a borderline or invasive ovarian tumour, treated by conservative surgery and desiring to become pregnant, the problem is thus of a possible resort to the Assisted Reproductive Technologies. PATIENTS AND METHODS: This is a multicenter, national and retrospective study. 40 operated patients between January 1971 and January 2001 have been included. 27 patients (67.5%) had a borderline tumour, 10 (25%) a non-epithelial tumour (germinal or stromal) and 3 (7.5%) an epithelial invasive carcinoma. All these patients have benefited from a conservative surgical management of fertility. The Assisted Reproductive Technologies were simple stimulation for 5 women and IVF for the 35 others. The effectiveness and the risks of Assisted Reproductive Technologies have been estimated respectively by the number of pregnancies obtained and the recurrence rates. RESULTS: With a global follow-up of 372 months (January 1971: date of the primary surgical procedure--June 2002: closing of the study), 17 patients have obtained 17 pregnancies with the Assisted Reproductive Technologies, rate of 42.5% (17/40): 1 spontaneous abortion, 16 delivery with 23 children (triple pregnancies and 3 twin pregnancies). 3 patients treated for a borderline tumour have had a recurrence after induction of ovulation. Among the 40 patients, no one presented an evolved disease at the last news. The patients who had a recurrence had a delay to begin the Assisted Reproductive Technologies significantly lower than the patients who had no recurrence. DISCUSSION AND CONCLUSION: The assisted reproductive technologies for patients who had been treated for a borderline or invasive ovarian tumour, and who were infertile in spite of conservative management, have allowed 42.5% of these women to obtain a pregnancy and does not seem to increase significantly the risk of recurrence.

Adult↗

Effects of larval exposure to sublethal concentrations of the ecdysteroid agonists RH-5849 and tebufenozide (RH-5992) on male reproductive physiology in Spodoptera litura.

Sublethal concentrations of the bisacylhydrazine moulting hormone agonists, RH-5849, and tebufenozide (RH-5992) were fed to sixth (final) instar larvae of Spodoptera litura. Both RH-5849 and tebufenozide adversely affected the mating success of S. litura when the surviving treated males were crossed with normal females. The ecdysone agonists decreased the longevity of treated males and of untreated females when crossed with treated males. The number of eggs laid by untreated females mated to treated males was decreased, and the fertility (percentage of hatching success) of the resulting eggs was reduced. These effects on male reproductive success were at least in part explained by a reduction in the number of sperm transferred during mating. The adverse effects of tebufenozide on male reproductive function were qualitatively the same as those of RH-5849, but tebufenozide was active at lower concentrations. To understand the reason for these adverse effects on male reproduction, we investigated the effects of the insecticides on male reproductive physiology. Male reproductive tract development and testicular volume of resulting adult moths were adversely affected by sublethal larval exposure to the ecdysone agonists. Dose-dependent reductions occurred in the production of eupyrene and apyrene spermatozoa in the adult testes, and in the number of spermatozoa released from the testes into the male reproductive tract. The descent into the male tract of both eupyrene and apyrene sperm was found to start at the normal stage of development in both normal and treated insects, but the daily rhythm of sperm descent was subsequently disturbed in the insecticide-treated moths. This affected the numbers of sperm in the upper vas deferens (UVD), seminal vesicle (SV), and duplex (duplex). Injections of RH-5849 given to pharate adult or newly emerged adult S. litura also caused drastic reduction in the number of sperm in the upper regions of the male tract, when measured 24 h after injection. The possible importance of pest population reduction through the sublethal anti-reproductive effects of insecticides is discussed.

Animals↗

When to parasitize? A dynamic optimization model of reproductive strategies in a cooperative breeder.

We consider a cooperatively breeding group and find the optimal pattern of reproductive parasitism by a subordinate helper as a function of its body size, and hence the share of reproduction obtained by the subordinate. We develop the model for the social system of the cooperatively breeding cichlid fish Neolamprologus pulcher but the general framework is also applicable to other cooperative systems. In addition to behaving cooperatively by sharing tasks, sexually mature male cichlid helpers may directly parasitize the reproduction of dominant breeders in the group. We investigate the relative influence of life history and behavioural variables including growth, parasitism capacity, future reproductive fitness benefits and costs, relatedness and expulsion risk on the optimal reproductive strategy of subordinates. In a detailed analysis of the parameter space we show that a male helper should base its decision to parasitize primarily on an increase in expulsion risk resulting from reproductive parasitism (punishment), intra-group relatedness and the parasitism capacity. If expulsion risk is high then helpers should not parasitize reproduction at medium body size but should parasitize either when small or large.

Animals↗

Effects of some environmental parameters on the reproduction and development of a tropical marine harpacticoid copepod Nitocra affinis f. californica Lang.

The effects of salinity, temperature, and light conditions on the reproduction and development of harpacticoid copepod, Nitocra affinis f. californica under controlled laboratory conditions were determined. Seven different salinity levels (5, 10, 15, 20, 25, 30, 35 ppt), four temperatures (20, 25, 30, 35 degrees C), three different light intensities (25, 56, 130 micromol m(-2) s(-1)) and photoperiods (24 h:0 h, 1 h:23 h, 12 h:12 h LD cycle) were employed in this study. The highest (p < 0.05) overall reproduction and fastest development time were achieved by copepods reared under 30-35 ppt salinity. The optimum temperature required for the maximum reproduction was 30 degrees C while under 30 degrees C and 35 degrees C the copepod development time was shortest (p < 0.05) compared to other temperature levels. The overall reproduction was highest (p < 0.05) and development rate of N. affinis was shortest (p < 0.05) under lowest light intensity (25 micromol m(-2) s(-1)). Continuous light (24 h:0 h LD) inhibited the egg production while, continuous darkness (1 h:23 h LD) and 12 h:12 h LD significantly favoured the overall reproductive activity of the female. Photoperiods 1 h:23 h and 12 h:12 h LD yielded highest total (p < 0.05) offspring female(-1) coupled with highest (p < 0.05) survival percentage. This study illustrated that although N. affinis can tolerate wide range of environmental conditions, prolonged exposure to subnormal environments affect its reproduction and development. This study showed that this species can be mass cultured for commercial purposes and has a potential to be used for toxicity studies due to its high reproductive performance fast development and a wide range of tolerance to environmental conditions.

Analysis of Variance↗

Reproductive and developmental toxicity of inhaled 2,3-dichloro-1,3-butadiene in rats.

Inhalation developmental and reproductive toxicity studies were conducted with 2,3-dichloro-1,3-butadiene (DCBD), a monomer used in the production of synthetic rubber. In the reproductive toxicity study, Crl:CD(SD)IGS BR rats (24/sex/group) were exposed whole body by inhalation to 0, 1, 5, or 50 ppm DCBD (6 h/day) for approximately 10-11 weeks total, through premating (8 weeks; 5 days/week), cohabitation of mating pairs (up to 2 weeks, 7 days/week), post-cohabitation for males (approximately 7 days) and from conception to implantation (gestation days 0-7 [GD 0-7]), followed by a recovery period (GD 8-21) for presumed pregnant females. Estrous cyclicity was evaluated during premating (last 3 weeks) and cohabitation. Reproductive organs and potential target organs, sperm parameters, and GD 21 fetuses (viability, weight, external alterations) were evaluated. In the developmental study, pregnant Crl:CD(SD)IGS BR rats (22/group) were exposed whole body by inhalation to 0, 1, 10, or 50 ppm DCBD (6 h/day) on GD 6-20; dams were necropsied on GD 21 (gross post-mortem only) and fetuses were evaluated (viability, weight, and external, visceral and skeletal exams). During the in-life portion of the studies, body weight, food consumption, and clinical observation data were collected. At 50 ppm, gasping and labored breathing occurred in both studies during the first few exposures; body weight and food consumption parameters were affected in parental animals from both studies, but were more severely affected in the developmental study. Fetal weight was decreased in the developmental study at 50 ppm. Degeneration of the nasal olfactory epithelium was observed in the reproduction study at 50 ppm. There were no effects on reproductive function, embryo-fetal viability, or increases in fetal structural alterations in either study. The no-observed-adverse-effect level (NOAEL) for reproductive toxicity was 50 ppm. The NOAEL for systemic toxicity in the reproduction study was 5 ppm based on adverse effects on body weight and food consumption parameters and nasal olfactory epithelial toxicity at 50 ppm in parental rats. The NOAEL for maternal and developmental toxicity was 10 ppm based on reduced maternal weight gain and food consumption and reduced fetal weight at 50 ppm in the developmental toxicity study.

Administration, Inhalation↗

Assessing reproductive status of right whales (Eubalaena glacialis) using fecal hormone metabolites.

Long-term studies of the endangered North Atlantic right whale, Eubalaena glacialis, have revealed declining reproductive parameters over the past two decades, threatening recovery of this small population if current trends continue. Little is known about right whale reproductive physiology, and investigating this reproductive decline has been limited by a lack of non-lethal methods for assessing reproductive status (e.g., sexual maturation, ovarian activity, pregnancy, lactation, and reproductive senescence) in free-swimming whales. This paper describes validation of existing radioimmunoassay techniques to study reproduction in right whales by measuring estrogens, progestins, androgens, and their related metabolites in fecal samples. Over the past decade fecal steroid hormone assays have been used to assess reproductive status and function in a wide range of terrestrial wildlife species, but this is the first application of this methodology in wild cetaceans. Analysis of fecal hormone metabolite levels in combination with life history data from photographically identified whales shows that this non-invasive method can be used to determine gender, detect pregnancy and lactation, and to assess age at sexual maturity in right whales and potentially other endangered whale populations.

Androgens↗

Perinatal and neonatal outcomes in multiple gestations: assisted reproduction versus spontaneous conception.

OBJECTIVE: Our purpose was to test the hypothesis that multiple pregnancies resulting from assisted reproductive therapy have a better outcome than those resulting from spontaneous conception. STUDY DESIGN: This was a retrospective cohort study. Cases came from pregnancies from assisted reproductive techniques. Controls were identified from spontaneous multiple pregnancies delivered in the same time period. Matching was done for maternal age, parity, fetal number, and presence of maternal medical problems. A total of 72 cases (56 twins and 16 triplets) and 124 controls (108 twins and 16 triplets) were studied. The primary outcome was perinatal mortality. Secondary outcomes were preterm delivery, birth weight, maternal complications, neonatal morbidity, and length of hospitalization. RESULTS: Perinatal mortality is significantly increased in spontaneous twin gestations compared with twins resulting from assisted reproductive techniques (24 vs 2, P =.003). No difference is seen in the perinatal mortality in triplets. Mean gestational age at diagnosis was lower for twins and triplets resulting from assisted reproductive techniques (9.4 vs 13.3; P <.001 and 8.8 vs 15. 8; P <.001, respectively). Rate of cerclage and number of prenatal visits was higher for triplets in the assisted reproductive techniques group (P =.05 and.02, respectively). Mean gestational age at delivery, birth weight, rate of preterm labor, preterm premature rupture of membranes, pregnancy-induced hypertension, and incidence of gestational diabetes were not significantly different between the groups. No significant differences in neonatal morbidity were detected. CONCLUSIONS: Assisted reproductive techniques-associated twins have lower perinatal mortality than spontaneously conceived twins. Perinatal and neonatal morbidity, gestational age at delivery, and birth weight are not affected by assisted reproductive techniques, even with closer surveillance and earlier gestational age at diagnosis in this group. Differences may be due to a higher frequency of monochorionic placentation in the spontaneously conceived group.

Adult↗

Leptin and reproduction: a review.

OBJECTIVE: To review recent advances in understanding the role of leptin in the physiology and pathophysiology of reproduction, with a focus on relevant clinical situations. DESIGN: A MEDLINE computer search was performed to identify relevant articles. RESULT(S): Leptin, an adipocyte hormone important in regulating energy homeostasis, interacts with the reproductive axis at multiple sites, with stimulatory effects at the hypothalamus and pituitary and inhibitory actions at the gonads. More recently, leptin has been shown to play a role in other target reproductive organs, such as the endometrium, placenta, and mammary gland, with corresponding influences on important physiologic processes such as menstruation, pregnancy, and lactation. As a marker of whether nutritional stores are adequate, leptin may act in concert with gonadotropins and the growth hormone axis to initiate the complex process of puberty. Conditions in which nutritional status is suboptimal, such as eating disorders, exercise-induced amenorrhea, and functional hypothalamic amenorrhea, are associated with low serum leptin levels; and conditions with excess energy stores or metabolic disturbances, such as obesity and polycystic ovarian syndrome, often have elevated serum or follicular fluid leptin levels, raising the possibility that relative leptin deficiency or resistance may be at least partly responsible for the reproductive abnormalities that occur with these conditions. CONCLUSION(S): Leptin may act as the critical link between adipose tissue and the reproductive system, indicating whether adequate energy reserves are present for normal reproductive function. Future interventional studies involving leptin administration are expected to further clarify this role of leptin and may provide new therapeutic options for the reproductive dysfunction associated with states of relative leptin deficiency or resistance.

Adipose Tissue↗

Effect of captivity in semi-natural enclosures on the reproductive endocrinology of female lizards.

Long-term captivity can result in abnormal behavior and physiology in many vertebrates. Here, we examine whether semi-natural, outdoor captive environments can offer a compromise, allowing much of the experimental control afforded by captivity, while providing the environmental conditions essential for normal behavior and physiology. We first determined plasma concentration of the sex steroid hormones progesterone, testosterone, and estradiol of free-ranging female striped plateau lizards (Sceloporus virgatus) throughout the reproductive season, and second, compared the results to those from conspecific females maintained in semi-natural outdoor enclosures. Among free-ranging females, levels of progesterone and estradiol were elevated during vitellogenesis, with an apparent surge in progesterone and testosterone occurring in association with ovulation. Following ovulation, estradiol fell to non-reproductive levels while progesterone remained elevated during the month-long period of gravidity. Long-term captivity in outdoor enclosures did not significantly affect progesterone or estradiol levels at any stage of the reproductive cycle, and did not affect testosterone levels during normal ovarian development and gravidity. However, (1) females with delayed oviposition in captivity had lower testosterone levels than free-ranging females with normal oviposition, and (2) when all females sampled were post-reproductive, captive females continued to have lower testosterone levels than free-ranging females. Thus, the endocrine response to captivity may be greater among post-reproductive females than among reproductive females. Our results are in marked contrast to many studies that show captivity can dramatically impair reproduction of female vertebrates.

Animals↗