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Reproductive endocrinology of female elasmobranchs: lessons from the little skate (Raja erinacea) and spiny dogfish (Squalus acanthias).

Conventional classification of reproductive modes in female elasmobranchs fails to account for the diversity in ovarian dynamics that operate during oviparous and viviparous cycles. Delineating this diversity is crucial for understanding the endocrine regulation of the manifold physiological mechanisms utilized to retain and protect eggs and developing embryos, to fuel embryogenesis, and to manage the intrauterine milieu. Oocyte development and follicular steroidogenesis overlap with egg retention and pregnancy in some species, whereas in others the follicular phase of the cycle is temporally separated from the gravid period. A luteal phase predominates the post-ovulatory period in viviparous species. In oviparous species, the luteal phase overlaps with the follicular cycle. This heterogeneity in ovulatory cycles suggests that the endocrine system evolved a transmutable system for regulating steroidogenesis and the control of the reproductive events. The reproductive biology and endocrinology of the oviparous little skate and lecithotrophic viviparous spiny dogfish are reviewed in order to derive a working hypothesis that explains the complex nature of endocrine patterns observed in species utilizing disparate reproductive modes. An understanding of the adaptations in ovarian dynamics to particular ovulatory cycles is key to developing theories about the evolution of reproductive strategies in female elasmobranchs. J. Exp. Zool. 284:557-574, 1999.

Animals↗

Environmental regulation of annual reproductive cycle in the mosquitofish, Gambusia affinis.

To clarify the environmental factors regulating the annual reproductive cycle of the female mosquitofish, Gambusia affinis, a viviparous teleost, histological changes of the ovary in natural population, and laboratory experiments were examined. The results, extending over two years, suggested that ovarian recrudescence is initiated by the rise in temperature during spring and that ovarian regression is caused by the shorter daylength during late summer. The first rearing experiments using four photoperiod-temperature groups to investigate the factors triggering the onset of reproduction revealed that females with regressing ovaries began reproduction with the rise of temperature regardless of the photoperiod during spring. The results of the second experiment using three different temperature groups indicated that vitellogenesis occurred at over 14 degrees C and pregnancy at over 18 degrees C. The third experiment with four photoperiod-temperature groups was arranged to investigate the factors in the cessation of reproduction. Sexually active females ceased vitellogenesis of the next clutch of oocytes due to the shorter daylength regardless of temperatures during late summer; however, temperature seemed to influence the rate of embryo development. The critical photoperiod is estimated at about 12.5 hr. In nature, it is supposed that vitellogenesis starts when the temperature rises to about 14 degrees C, and final maturation of oocytes occurs when the temperature reaches about 18 degrees C during spring. Then, vitellogenesis of the next clutch of oocytes ceases when the daylength becomes shorter than 12.5 hr during late summer; the last gestation proceeds at a rate dependent on the temperature, and finally reproduction ends by the last parturition. J. Exp. Zool. 286:204-211, 2000.

Animals↗

Women's reproductive health: some recent developments in occupational epidemiology.

Epidemiological research on occupational hazards and reproductive health is an expanding and strongly developing area. This article focuses on some recent areas of occupational reproductive epidemiology that are or seem to be important for the future. Interest in the research on fertility has increased during the past decade, and time to pregnancy has proved to be a useful measure of fertility. The research on menstrual function or early fetal loss is still limited, and further research is desirable. It is important to chart the advantages and disadvantages of various methods for measuring these outcomes. Recently developed methods of exposure assessment provide new possibilities to improve the validity of exposure data. Biological exposure markers can also provide useful dosimeters for reproductive studies. Research on the reproductive effects of job stress and individual susceptibility to reproductive toxicants is also gaining in importance.

Disease Susceptibility↗

Two-generation reproduction and developmental neurotoxicity study with sodium chlorite in the rat.

The potential for sodium chlorite to produce reproductive toxicity, developmental neurotoxicity and alterations in hematology and thyroid hormones was evaluated in Sprague-Dawley rats administered sodium chlorite in the drinking water continuously for two generations. The F(0) generation animals (30 of each gender per group) and F(1) generation animals (25 of each gender per group) selected to rear the F(2) generation were allowed free access to drinking water containing 0, 35, 70 or 300 ppm sodium chlorite for a 10-week prebreed period, through mating for males and through mating, gestation and lactation for females. These drinking water concentrations corresponded to sodium chlorite doses of approximately 4, 8 and 30 mg kg(-1) day(-1) for males and 5, 10 and 39 mg kg(-1) day(-1) for females, respectively. Evaluations included standard reproductive and postnatal indices, sperm morphology and motility, estrous cyclicity, a functional observational battery, motor activity, auditory startle, swim maze, hematology, serum thyroid hormone analyses and histopathology of reproductive and nervous system tissues. Sodium chlorite resulted in a decrease in water consumption in all groups and a decrease in food consumption and body weights in the 70 and 300 ppm groups. There was no evidence of reproductive toxicity. Pup body weight was decreased in the 300 ppm group and small delays were observed in the time to preputial separation and vaginal opening. Mild anemia and mild methemoglobinemia were observed for animals in the 300 ppm group. Thyroid hormone levels were not affected by treatment. Changes to the nervous system were limited to small decreases in amplitude of auditory startle response for postnatal day (PND) 25 pups in the 70 and 300 ppm groups and a small decrease in absolute brain weight for PND 11 pups in the 300 ppm group. These effects were considered to be of questionable neurotoxicological significance. Based on the results of this study, the no-observed-effect level (NOEL) for effects on reproduction and thyroid hormones is 300 ppm. The no-observed-adverse-effect levels (NOAEL) for hematological toxicity and neurotoxicity are considered to be 70 and 300 ppm, respectively.

Analysis of Variance↗

Studies on the reproductive effects of Fusarium moniliforme culture material in rats and the biodistribution of [14C] fumonisin B1 in pregnant rats.

Fumonisins are mycotoxins produced by Fusarium moniliforme and other Fusarium species. They are commonly found in corn and corn-based foodstuffs. Fumonisins inhibit sphingolipid (SL) biosynthesis, alter cellular SL profiles, and thus may affect cell proliferation and differentiation, both of which are important processes for reproduction. However, there are few reports of the effects of F. moniliforme or fumonisins on mammalian reproduction or development. To study the reproductive effects of this fungus, diets formulated with culture material of toxic F. moniliforme strain MRC 826 (CM) to provide 0, 1, 10, or 55 ppm fumonisin B1 (FB1) were fed to male and female rats beginning 9 and 2 weeks before mating, respectively, and continuing throughout mating, gestational, and lactational phases of the study. CM caused nephropathy, typical of FB1, in males fed > or = 10 ppm and females fed 55 ppm FB1. No significant reproductive effects were found in males (n = 12/group), dams, and fetuses examined on gestation day 15 (G15) (n > or = 8/group), or dams and litters through day 21 postpartum (n > or = 9/group). Litter weight gain in the 10 or 55 ppm FB1 groups was slightly decreased; however, gross litter weight and physical development of offspring were not affected. Altered SL ratios indicative of fumonisin exposure, specifically increased sphinganine to sphingosine ratios, were found in the livers of dams from the 55-ppm FB1 group on G15. However, SL ratios of abdominal slices, containing liver and kidney, of fetuses from control and high-dose litters did not differ. In a second experiment, two dams were injected intravenously on G15 with 101 micrograms [14C]FB1 (3.179 x 10(5) dpm). After 1 hr, which allowed for ca. 98% of the dose to be cleared from the maternal blood, negligible amounts of radioactivity were found in the fetuses. Together, these results indicate that the CM, and by inference FB1, did not have significant reproductive effects at doses which are minimally toxic, and further suggest that little in utero FB1 exposure occurred through G15.

Animals↗

Early developmental conditions and reproductive success in humans: downstream effects of prenatal famine, birthweight, and timing of birth.

Growth, survival, and breeding success of individuals in populations of wild mammals are influenced by the climatic and nutritional conditions that individuals experience during their early development. Recent findings have shown that early conditions also have consequences for subsequent survival and reproductive performance in humans. Environmental conditions which affect early development of individuals, such as the quality and quantity of nutrition received in utero and infancy, predict the onset of many chronic diseases in adulthood, affect longevity and may also influence a range of measures of reproductive performance in both food-limited and contemporary Western human populations. These associations are proposed to result from foetal programming, where a stimulus or insult during a critical period early in life may permanently affect body structure, physiology, and metabolism. Here I review studies showing how birthweight, season of birth, or exposure to prenatal starvation affect different aspects of an individual's subsequent reproductive success in humans and the growth, survival, and reproductive performance of the offspring produced. I show that early maternal and environmental conditions can have a large impact on human reproductive strategies and fitness that can span across generations.

Birth Weight↗

Reproductive hazards of fire fighting. I. Non-chemical hazards.

Fire fighters are regularly exposed to chemical and non-chemical agents that have known or suspected adverse effects on reproductive health. Although chemical agents have received some attention, non-chemical hazards such as heat, noise, and physical exertion have only recently been examined for their reproductive effects. There is evidence that heat, noise, and physical exertion may affect various endpoints of reproductive health, including fertility, fetal loss, and growth parameters of the offspring. In particular, hyperthermia, a major fire fighting hazard, has been shown to impair male fertility and may also be teratogenic. Further study of the potential reproductive effects of this and other common non-chemical agents in the fire environment is needed to ensure the reproductive health of male and female fire fighters.

Animals↗

Reproductive hazards of fire fighting. II. Chemical hazards.

Studies of the health of fire fighters have historically focused on non-malignant respiratory disease and cancer. More recently, concerns have surfaced about reproductive health effects in many areas of the workforce, including fire fighting. These concerns prompted this review of chemical exposures that may contribute to adverse reproductive health outcomes in male as well as female fire fighters. A review of the industrial hygiene literature was undertaken to identify agents commonly found in fire smoke. These agents were then examined for evidence of reproductive toxicity or mutagenicity/carcinogenicity. This profile of chemical agents and their reproductive toxicities permits a qualitative determination that fire fighters are exposed to potential reproductive toxicants as a part of their normal fire fighting duties. Considerations for mitigating these risks are also discussed.

Air Pollutants, Occupational↗

Analysis of reproductive health hazard information on material safety data sheets for lead and the ethylene glycol ethers.

Material Safety Data Sheets (MSDSs) are essential sources of information regarding health risks from exposure to toxic chemicals. We analyzed the reproductive health hazard descriptions on nearly 700 MSDSs for lead- or ethylene glycol ether-containing products submitted by central Massachusetts firms to the Department of Environmental Protection under provisions of the Massachusetts Right-to-Know Law. Over 60% of the MSDSs made no mention whatsoever of effects on the reproductive system. Those that did were much more likely to address developmental risks than male reproductive effects. The MSDSs from firms employing 100 or more workers mentioned reproductive system effects more frequently than those from smaller companies. While the informativeness of the health hazard descriptions increased over time, 53% of the MSDSs prepared after promulgation of the OSHA Hazard Communication Standard still contained no information on reproductive risks.

Chemical Industry↗

Characteristics of reproductive biology and proximate factors regulating seasonal breeding in captive golden-headed lion tamarins (Leontopithecus chrysomelas).

Reproduction is highly demanding in terms of energy expenditure, and the costs and benefits associated with postponing or investing in a reproductive effort are crucial determinants of an individual's fitness. Understanding the reproductive potential of a species under varying ecological conditions offers important insights into the dynamics of its social system. This study provides the first detailed analysis of the reproductive potential of wild- and captive-born golden-headed lion tamarins (Leontopithecus chrysomelas) under captive conditions, based on studbook data compiled during 1984-2000. Litters produced by wild-born females breeding in captivity are similar in size to litters observed in the wild, but smaller than litters of captive-born females. The more stringent ecological conditions experienced by wild-born females during maturation may result in a lifelong effect on litter size. However, interbirth intervals are shorter for wild-born than captive-born females. The relatively smaller burden of infant care that results from having smaller litters may allow wild-born females to sustain the next pregnancy sooner. Reproduction in the Brazilian captive population is highly seasonal for both wild-born females and females born in captivity in Brazil. Changes in photoperiod over a year provide a proximate explanation for changes in the proportion of conceptions and births per month. Outside Brazil, breeding occurs year-round, and no clear birth peak is apparent. Information from field reports that could be used to relate this finding to ecological factors, such as resource availability, is unavailable.

Animals↗

Influence of the mother's reproductive state on the hormonal status of daughters in marmosets (Callithrix kuhlii).

Behavioral and endocrine suppression of reproduction in subordinate females produces the high reproductive skew that characterizes callitrichid primate mating systems. Snowdon et al. [American Journal of Primatology 31:11-21, 1993] reported that the eldest daughters in tamarin families exhibit further endocrinological suppression immediately following the birth of siblings, and suggested that dominant females exert greater control over subordinate endocrinology during this energetically challenging phase of reproduction. We monitored the endocrine status of five Wied's black tufted-ear marmoset daughters before and after their mother delivered infants by measuring concentrations of urinary estradiol (E(2)), pregnanediol glucuronide (PdG), testosterone (T), and cortisol (CORT). Samples were collected from marmoset daughters 4 weeks prior to and 9 weeks following three consecutive sibling-litter births when the daughters were prepubertal (M=6.1 months of age), peripubertal (M=11.9 months), and postpubertal (M=17.6 months). The birth of infants was associated with reduced ovarian steroid excretion only in the prepubertal daughters. In contrast, ovarian steroid levels tended to increase in the postpubertal daughters. Urinary E(2) and T levels in the postpubertal daughters were 73.8% and 37.6% higher, respectively, in the 3 weeks following the birth of infants, relative to prepartum levels. In addition, peak urinary PdG concentrations in peri- and postpubertal daughters were equivalent to luteal phase concentrations in nonpregnant, breeding adult females, and all of the peri- and postpubertal daughters showed clear ovulatory cycles. Cortisol excretion did not change in response to the reproductive status of the mother, nor did the concentrations change across age. Our data suggest that marmoset daughters of potential breeding age are not hormonally suppressed during the mother's peripartum period or her return to fertility. These findings provide an additional example of species diversity in the social regulation of reproduction in callitrichid primates.

Animals↗

Reproductive toxicity assessment of lasofoxifene, a selective estrogen receptor modulator (SERM), in male rats.

BACKGROUND: Lasofoxifene is a nonsteroidal selective estrogen receptor modulator (SERM) with greater than 100-fold selectivity against all other steroid receptors and is a potentially superior treatment for postmenopausal osteoporosis. The purpose of this study was to evaluate the effects of lasofoxifene on male reproduction in rats in light of the known effects of estrogen modulating compounds on male reproductive ability. METHODS: Lasofoxifene was administered to adult male rats at doses of 0.1, 1, 10, and 100 mg/kg for 66-70 consecutive days. After 28 days of dosing, male rats were cohabited with untreated female rats. Female rats were euthanized on gestation day 14 and a uterine examination was carried out for evaluation of reproductive parameters and embryo viability. Male rats were euthanized after 66-70 days of dosing and epididymal sperm motility and concentration were assayed. The testes, epididymides, prostate, and seminal vesicles were weighed and microscopically examined. RESULTS: The duration of cohabitation was increased for 100 mg/kg males by 0.7 days. The number of males copulating and the number of implantation sites produced per copulation were reduced in the 10 and 100 mg/kg groups. Weights of the seminal vesicles and epididymides were reduced for all groups, although the testes weight and epididymal sperm motility and concentration were not affected by treatment. There were no microscopic findings in the male reproductive tissues. CONCLUSION: The changes in male fertility and reproductive tissue weights after exposure to lasofoxifene are consistent with those previously described for estrogen receptor-modulating compounds.

Animals↗

Effects of human and murine antisense oligonucleotide inhibitors of ICAM-1 on reproductive performance, fetal development, and post-natal development in mice.

The potential for reproductive toxicity of an antisense oligonucleotide designed to inhibit ICAM-1 was evaluated as part of the safety assessment for this compound. Since antisense compounds are often specific to the species in which they are intended to work, both the human and murine active ICAM-1 inhibitors were tested (ISIS 2302 and ISIS 3082, respectively). Male and female mice were treated prior to cohabitation, through cohabitation, gestation, delivery, and weaning. Mice were treated with 0, 3, 6, and 12 mg/kg ISIS 2302 or ISIS 3082 by daily i.v. injection. Reproductive indices evaluated included estrus cycling, sperm count and motility, fertility, litter parameters, fetal development, delivery, fetal body weight, lactation, and weaning. Behavioral assessment and reproductive capacity of the F1 generation mice was assessed on selected animals. Concentrations of oligonucleotide in selected maternal target organs, placenta, fetal tissues, and expressed milk were also measured. There were no changes in reproductive performance, litter parameters, fetal development, or postnatal development in mice treated with either ISIS 2302 or ISIS 3082. Maternal liver and kidney contained dose-dependent concentrations of oligonucleotide, but there was relatively little or no oligonucleotide measured in placenta, fetal tissues, or expressed milk. Neither the human nor murine-specific antisense inhibitor of ICAM-1 produced any reproductive toxicity in mice, and exposure of fetus or pups was negligible.

Animals↗

The relationship between reproductive state and "sexually" dimorphic brain areas in sexually reproducing and parthenogenetic whiptail lizards.

The anterior hypothalamus-preoptic area and ventromedial hypothalamus are sexually dimorphic in the reproductively active whiptail lizard Cnemidophorus inornatus. The anterior hypothalamus-preoptic area, which is involved in the control of male-typical copulatory behaviors, is larger in males, whereas the ventromedial hypothalamus, which is involved in the control of female-typical receptivity, is larger in females. In the parthenogenetic whiptail lizard C. uniparens, which is a direct descendant of C. inornatus and exhibits both male-like and female-like pseudosexual behaviors, both brain areas are comparable in size to those of female C. inornatus. This study was conducted to determine whether these brain areas change in size in either species or sex during a time of year when these animals are reproductively inactive, or after removal of the gonads. In male C. inornatus both brain areas changed during reproductive inactivity (either seasonally or surgically induced) and became equivalent to the size characteristic of reproductively active female C. inornatus. When corrected for brain size, the anterior hypothalamus-preoptic area was significantly smaller in intact hibernating and castrated males than in intact males from the summer breeding season. Conversely, the ventromedial hypothalamus was significantly larger in intact hibernating and castrated males than in intact males from the summer breeding season. The two brain areas were not significantly different among the groups of female C. inornatus or parthenogenetic C. uniparens. These results suggest that 1) the brain of whiptail lizards may differentiate seasonally and 2) the female state may be a neutral one to which the male brain reverts during reproductive inactivity.

Aging↗

Advantages of sexual reproduction.

Despite the obvious efficiencies of many forms of asexual reproduction, sexual reproduction abounds. Asexual species, for the most part, are relatively short-lived offshoots of sexual ancestors. From the nineteenth century, it has been recognized that, since there is no obvious advantage to the individuals involved, the advantages of sexual reproduction must be evolutionary. Furthermore, the advantage must be substantial; for example, producing males entails a two-fold cost, compared to dispensing with them and reproducing by parthenogenetic females. There are a large number of plausible hypotheses. To me the most convincing of these are two. The first hypothesis, and the oldest, is that sexual reproduction offers the opportunity to produce recombinant types that can make the population better able to keep up with changes in the environment. Although the subject of a great deal of work, and despite its great plausibility, the hypothesis has been very difficult to test by critical observations or experiments. Second, species with recombination can bunch harmful mutations together and eliminate several in a single "genetic death." Asexual species, can eliminate them only in the same genotype in which they occurred. If the rate of occurrence of deleterious mutations is one or more per zygote, some mechanism for eliminating them efficiently must exist. A test of this mutation load hypothesis for sexual reproduction, then, is to find whether deleterious mutation rates in general are this high--as Drosophila data argue. Unfortunately, although molecular and evolutionary studies can give information on the total mutation rate, they cannot determine what fraction are deleterious. In addition, there are short discussions of the advantages of diploidy, anisogamy, and separate sexes.

Adaptation, Physiological↗

Influence of photoperiod, ambient temperature and melatonin on testosterone synthesis and release during reproductive maturation in male deer mice.

Four experiments were designed to investigate the influence of photoperiod and other environmental factors on androgen production and reproductive maturation in deer mice. Male prairie deer mice (Peromyscus maniculatus), born in a light/dark cycle of 6L:18D, either remained in this short photoperiod or were switched to a long day regimen of 16L:8D at weaning. In a cross-sectional experiment, the deer mice were killed between 3 and 8 weeks of age for measurement of serum testosterone concentration and reproductive organ weights. In a second experiment, blood was collected from each mouse at weekly intervals between 3 and 9 weeks of age. This repeated measures design was used to reduce the high variability in testosterone values observed in the first experiment. Reproductive organs were weighed at the termination of the experiment. Testosterone concentrations and reproductive organ weights were greater in males reared in the long photoperiod in both experiments. In a third experiment, the animals were housed under five different conditions to test the influence of high ambient temperature and melatonin as well as photoperiod. At 7 weeks of age, they received an injection of hCG or saline. More testosterone was released in deer mice reared in 16L:8D and 27 C than in those reared in short days (6L:18D) or those reared in high ambient temperature (35 C) or those treated with exogenous melatonin. One week later, animals were sacrificed. The single hCG treatment caused significant reversal of the suppression of accessory sex organ weights following melatonin, short days or 35 C temperature. In a fourth experiment, the additive influence of melatonin and 35 C temperature was tested. Animals treated with 35 C or both melatonin and 35 C had lower serum testosterone at 7 weeks of age, released less testosterone after hCG, and had smaller organ weights with or without hCG than long day controls. The influence of melatonin treatment and 35 C temperature appears to be additive for testicular weight and testosterone release after hCG. Thus, the attenuation of reproductive development that accompanied short days, melatonin treatment and high ambient temperature occurred via diminished testosterone secretion, which can be overcome at least in part by gonadotropin treatment.

Animals↗

Evaluation of a reproductive toxicity assay using Xenopus laevis: boric acid, cadmium and ethylene glycol monomethyl ether.

Cadmium (Cd), boric acid (BA) and ethylene glycol monomethyl ether (EGME) were evaluated for reproductive and developmental toxicity in Xenopus laevis. Eight reproductively mature adult male and eight superovulated female Xenopus laevis were exposed to at least five separate sublethal concentrations of each material via the culture water for a period of 30 days. Four respective pairs were mated and the offspring evaluated for developmental effects; an evaluation of reproductive status was performed on the remaining four specimens. Ovary pathology, oocyte count, oocyte maturity and maturation capacity (germinal vesicle breakdown, GVBD) and necrosis were evaluated in the female, whereas testis pathology, sperm count, dysmorphology and motility were studied in the male. Based on this assessment, each test material exerted reproductive toxicity in Xenopus laevis, but with varying potencies. Adult female exposure to Cd and EGME particularly, and to a lesser extent to BA, resulted in transgenerational toxicity to the developing progeny. Further, this model appears to be a useful tool in the initial assessment and prioritization of potential reproductive toxicants for further testing.

Abnormalities, Drug-Induced↗

Argemone oil induced cellular damage in the reproductive tissues of transgenic Drosophila melanogaster: protective role of 70 kDa heat shock protein.

We explored the reproductive toxicity of argemone oil and its principal alkaloid fraction in transgenic Drosophila melanogaster (hsp70-lacZ) Bg(9). The toxicity of argemone oil has been attributed to two of its physiologically active benzophenanthridine alkaloids, sanguinarine and dihydrosanguinarine. Freshly eclosed first instar larvae of transgenic Drosophila melanogaster were transferred to different concentrations of argemone oil and its alkaloid fraction contaminated food. Virgin flies that eclosed from the contaminated food were pair-mated to look into the effect on reproduction. The study was further extended by investigating hsp70 expression and tissue damage in larval gonads, genital discs, and reproductive organs of adult fly. Our results showed that argemone oil was more cytotoxic than its principal alkaloid fraction. Moreover, it was the male fly that was more affected compared to its opposite number. The accessory glands of male reproductive system of the fly, which did not express hsp70, exhibited severe damage as evidenced by Trypan blue staining. This prompted us to explore the ultrastructural morphology of the gland, which showed acute signs of necrosis in both the cell types as evident by necrotic nuclei, higher vacuolization, and disorganized endoplasmic reticulum, decrease in the number of Golgi vesicles and disorganized, loosely packed filamentous structures in the lumen of the accessory gland, at the higher concentrations of the adulterant. The study showed the reproductive toxicity of argemone oil and its alkaloid fraction in transgenic Drosophila melanogaster and further confirmed the cytoprotective role of hsp70.

Alkaloids↗