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Stress and behaviorally induced reproductive dysfunction in primates.

Both acute and chronic psychological and social stresses can impair reproductive hormone secretion in a variety of nonhuman primate species. This impairment can be subtle, consisting of a mild suppression in reproductive hormone secretion, or dramatic, underlying a complete suppression of fertility and reproductive behavior. Although group mean responses to various stresses can be measured, it is clear that there are marked differences in the response of the reproductive axis to these stresses among individual animals. Factors that contribute to the variability in the response of the reproductive axis include the type of stress, the magnitude and duration of stress, the perception of the stress by the individual, the social status of the individual, the concurrent level of aggressive behavior displayed by the individual, seasonal cues, and the prior level of activity within the reproductive axis. During some stresses, activation of the adrenal axis, endogenous opioid pathways, increased prolactin release, and changes in sensitivity to gonadal steroid hormone feedback appear to play a role in mediating the effects of behaviorally induced stresses on the reproductive axis. However, a great deal more work is needed to understand the mechanisms underlying impairment of the reproductive axis by most psychological and social stresses, as well as the mechanisms underlying differences in susceptibility to stress-induced impairment of reproductive function within individuals.

Animals↗

Functional interactions between estrogen and insulin-like growth factor-I in the regulation of alpha 1B-adrenoceptors and female reproductive function.

The ovarian hormone estradiol (E(2)) and insulin-like growth factor-I (IGF-I) interact in the CNS to regulate neuroendocrine function and synaptic remodeling. Previously, our laboratory showed that 2 d E(2) treatment induces alpha(1B)-adrenoceptor expression and promotes IGF-I enhancement of alpha(1)-adrenoceptor potentiation of cAMP accumulation in the preoptic area (POA) and hypothalamus (HYP). This study examined the hypothesis that E(2)-dependent aspects of female reproductive function, including alpha(1B)-adrenoceptor expression and function in the POA and HYP, are mediated by brain IGF-I receptors (IGF-IRs) in female rats. Ovariohysterectomized rats were implanted with a guide cannula aimed at the third ventricle and treated in vivo with vehicle or E(2) daily for 2 d before experimentation. Intracerebroventricular infusions of JB-1, a selective IGF-IR antagonist, were administered every 12 hr beginning 1 hr before the first E(2) injection. Administration of JB-1 during E(2) priming completely blocks hormone-induced luteinizing hormone release and partially inhibits hormone-dependent reproductive behavior. Reproductive behavior is restored by intracerebroventricular infusion of 8-bromo-cGMP, the second messenger implicated in alpha(1)-adrenergic facilitation of lordosis. In addition, blockade of IGF-IRs during E(2) priming prevents E(2)-induced increases in alpha(1B)-adenoceptor binding density and abolishes acute IGF-I enhancement of NE-stimulated cAMP accumulation in HYP and POA slices. These data document the existence of a novel mechanism by which IGF-I participates in the remodeling of noradrenergic receptor signaling in the HYP and POA after E(2) treatment. These events may help coordinate the timing of ovulation with the expression of sexual receptivity.

Adrenergic alpha-1 Receptor Antagonists↗

Behavioral and reproductive differences in mice as a function of inbreeding.

Twenty brother-sister pairs of mice were randomly selected from a genetically heterogeneous population of mice to begin a schedule of inbreeding that lasted for six generations (F = 0 to F = .732). We examined a number of indices of reproductive behavior and found that all declined as a function of inbreeding. Specifically, there was a consistent decline in the number of fertile matings, in the number of offspring that survived to weaning, and in the weight of the pups at the time of weaning (21 days of age). We also examined a number of behaviors with the following results: there was a systematic increase in the number of trials required to learn an active avoidance task and a consistent decrease in the number of trials required to extinguish this habit. We observed a statistically significant difference in the retention of a passive avoidance habit, but these results were quite variable and not consistent across generations of inbreeding. Finally, we observed that inbreeding had little effect on measures of locomotor behavior.

Animals↗

Genetically heterogeneous and selected lines of rats: behavioral and reproductive comparison.

Avoidance learning, open-field, and reproductive behaviors of a genetically heterogeneous stock (derived from a four-way cross of selected lines) were compared with the corresponding behaviors of the parental lines. The heterogeneous stock showed heterosis on the body development, fertility rate, litter size at birth and at weaning, and directional dominance on the avoidance learning and open-field measures.

Animals↗

Fertility behavior and reproductive outcomes among young Guatemalan adults.

Fertility rates have declined in many developing countries and this has implications for health and development of subsequent generations. Guatemala has the highest fertility rates in Central America. Reproductive histories were obtained by interview in 2002-04, in a cohort of 779 women and 647 men who had participated as young children in a nutrition supplementation trial in Guatemala conducted between 1969 and 1977. Most women (77%) and men (79%) are currently married. Among the 700 women and 524 men reporting at least one birth, mean age at first birth was 20.7 +/- 3.8 years and 23.1 +/- 3.9 years respectively. Knowledge (> 80%) and use (approximately 70%) of modern contraceptive methods is fairly high; knowledge increases with parental socioeconomic status (SES) as measured in 1975. Younger respondents have experienced fewer pregnancies and live births compared with older respondents; age-specific fertility rates between 20 and 24 years were 294, 249, 236, and 261 births per 1,000 women, respectively, for women born from 1962-65, 1966-69, 1969-73, and 1974-77. Women in the top tertile of parental SES have had significantly fewer pregnancies (3.3) compared with those in the middle (3.7) and lower (3.8) tertiles. Migrants to Guatemala City reported greater knowledge of contraceptive methods, fewer pregnancies and living children, higher age at first birth, and more pregnancy and newborn complications as compared with cohort members who remained in the original villages (p < .05 for each comparison). Fertility rates, especially between 20 and 24 years, have declined over time. Differences in reproductive behaviors by parental SES and current residence suggest the role of social transitions in determining family formation in Guatemala.

Abortion, Induced↗

Alterations to gonadal development and reproductive success in Japanese medaka (Oryzias latipes) exposed to 17alpha-ethinylestradiol.

The Japanese medaka (Oryzias latipes) was used as an in vivo model to evaluate the effects of exposure to the synthetic estrogen 17alpha-ethinylestradiol (EE2) on reproductive behavior and reproductive success in fish. Exposures to EE2 began within 2 to 5 d posthatch and continued until medaka were sexually mature, between four and six months of age. Among male and female medaka exposed to EE2 at nominal concentrations of 0.2 and 2 ng/L, mating behavior and reproductive success were normal in reproductive trials. However, reproductive behavior (i.e., copulations) was suppressed in the treatment with 10 ng/L EE2. Among 19 males exposed to 10 ng/L EE2 and placed with unexposed females in reproductive trials, 16 males did not copulate and reproductive success was very low. None of the females exposed to 10 ng/L of EE2 participated in reproductive behavior with unexposed males. The reproductive trials in combination with a histological survey indicated that male fish with gonadal intersex (i.e., testis-ova) were still capable of reproductive behavior and could fertilize eggs. Even though females exposed to 10 ng/L EE2 had poor reproductive success, their ovaries showed normal development and oogenesis. These data are relevant to observations of intersex in feral fish populations. Although intersex in male fish may be an indicator of exposure to estrogenic compounds, it appears that the presence of oocytes in testicular tissue may not directly impact the reproductive capability of the male fish. However, it is clear that concentrations of endocrine disrupting chemicals (EDCs) that cause gonadal intersex are sufficient to reduce reproductive performance.

Animals↗

Effects of neonatal resveratrol exposure on adult male and female reproductive physiology and behavior.

Resveratrol (RES) is a phytoestrogen that has the ability to bind to estrogen receptors (ERs) and evoke biological effects that parallel those exerted by endogenous and synthetic estrogens. We have shown in previous studies that adult female rats acutely exposed to RES exhibit estrous cycle irregularity, ovarian hypertrophy, and alterations in sociosexual behavior. The present experiment characterizes the prolonged effects of maternal RES exposure throughout the lactational period on subsequent behavior, reproductive tissues, and brain morphology of the adult offspring. During adulthood, female offspring exposed to RES throughout nursing exhibited reduced body weight and increased ovarian weight, but exhibited normal estrous cyclicity and sociosexual behavior, without changes in the volume of the sexually dimorphic nucleus of the preoptic area or the anteroventral periventricular nucleus of the hypothalamus. During adulthood, males exposed to RES throughout nursing exhibited decreased body weight and plasma testosterone concentration, increased testicular weight, and reduced sociosexual behavior. These males also had significantly smaller sexually dimorphic nucleus of the preoptic area volumes and larger anteroventral periventricular nucleus volumes compared to male controls. These data suggest that postnatal exposure to RES may affect estrogenic activity in specific peripheral tissues (e.g., the gonads), while inducing antiestrogenic effects in the brain. Thus, the present study supports recent in vitro and in vivo findings that RES differs from most other phytoestrogens by acting as a possible mixed ER agonist/antagonist, depending on the tissue-specific availability of ER subtypes that are preferentially localized in specific brain regions and throughout the reproductive tract. More importantly these data indicate that maternal consumption of phytoestrogens during lactation can have lasting effects on the offspring that may not become apparent until they reach adulthood.

Animals↗

Expression of the SCAMP-4 gene, a new member of the secretory carrier membrane protein family, is repressed by progesterone in brain regions associated with female sexual behavior.

Rodent female reproductive behavior is facilitated by the genomic targets of estrogen (E) and progesterone (P) in neuroendocrine regions of the brain. Using the differential display-PCR technique to identify these targets we discovered a novel hormone-sensitive mRNA in the female rat brain that is substantially reduced in the ventromedial hypothalamus (VMH) after 3 h of P treatment, following 24 h of E priming. Northern blots show that it is a single transcript of approximately 1.7 kb. The sequence of the corresponding full-length cDNA indicates that this gene is the rat homolog of mouse SCAMP-4, the fourth member identified in a family of proteins known as secretory carrier membrane proteins (SCAMPs). In situ hybridization studies show that SCAMP-4 mRNA is relatively low throughout the rat forebrain, with the highest levels observed in the VMH, habenula and hippocampus. The SCAMP-4 message is also less abundant in the habenula and VMH during proestrus, when circulating levels of E and P are at their peak, than during diestrus-1 when circulating hormone levels are low. Amino acid sequence analysis indicates that SCAMP-4 lacks the putative calcium binding and leucine zipper structures, as well as protein-protein interacting NPF domains common among most SCAMP family members, but is the only member identified to date to contain a putative protein kinase C (PKC) phosphorylation site. Fluorescent microscopy of cells transfected with a SCAMP-4/GFP fusion construct reveals distinct fluorescence in subcellular aggregates that may contain secretory vesicles. In addition to our results in the VMH, the finding of high levels of SCAMP-4 message in the habenula, a brain area rich in mast cells, together with previous reports linking mast cell secretion with courtship behavior also suggest a possible role for SCAMP-4 in reproductive behaviors associated with mast cell activity in the central nervous system (CNS).

Amino Acid Sequence↗

Reproduction-related behaviors of Swiss-Webster female mice living in a cold environment.

Based on a molecular neuroendocrine theory about cold environments, thyroid hormone levels, and liganded thyroid hormone receptor interference with estrogen receptor function, experiments were designed to test female mouse reproductive behaviors in the cold. Because natural seasonal temperature declines would usually be associated with decreased photoperiods and reduced food supplies, we combined cold temperatures with short days and metabolic challenge. The simplest hypothesis was that lordosis quotients would be significantly reduced as a result of cold temperatures. That hypothesis was denied. Instead, female approaches to the stud male declined. Because cold temperatures also led to significant reductions of activity in locomotor wheels, a straightforward reduction of activity could explain the female's behavior during mating tests. We suggest that cold temperatures accompanied by reduced photoperiod and reduced metabolic fuel can reduce overall activity in female mice, thus indirectly blocking untimely reproductive behaviors.

Adaptation, Physiological↗

Evolution of the army ant syndrome: the origin and long-term evolutionary stasis of a complex of behavioral and reproductive adaptations.

The army ant syndrome of behavioral and reproductive traits (obligate collective foraging, nomadism, and highly specialized queens) has allowed these organisms to become the premiere social hunters of the tropics, yet we know little about how or why these strategies evolved. The currently accepted view holds that army ants evolved multiple times on separate continents. I generated data from three nuclear genes, a mitochondrial gene, and morphology to test this hypothesis. Results strongly indicate that the suite of behavioral and reproductive adaptations found in army ants throughout the world is inherited from a unique common ancestor, and did not evolve convergently in the New World and Old World as previously thought. New Bayesian methodology for dating the antiquity of lineages by using a combination of fossil and molecular information places the origin of army ants in the mid-Cretaceous, consistent with a Gondwanan origin. Because no known army ant species lacks any component of the army ant syndrome, this group represents an extraordinary case of long-term evolutionary stasis in these adaptations.

Adaptation, Physiological↗

Behavioral and environmental determinants of reproductive success in traditional Moroccan Berber groups.

The reproductive histories of women aged 45-70 years from a homogeneous Berber population of South Morocco were sampled from three contrasting environments: a small town (n = 75), villages in the lowlands (n = 217), and villages in the highlands (n = 128). The main reproductive variables oppose the relatively better conditions of fertile life in the lowlands to the more hostile ones in the highlands. Path analysis confirms this difference through reproductive behaviors and suggests the existence of mechanisms for controlling family size in town and in the rural lowlands, but not in the highlands. The estimates of survival function show significant differences among the three groups, the conditions for survival in the highlands being clearly less favorable. Rank tests of the association of survival data with several covariates indicate the association of survival data with vaccinations and with conditions of delivery. In spite of the lower rate of offspring survival, the highlander group would demonstrate a higher overall number of children reaching reproductive maturity, thanks to an extended reproductive span.

Aged↗

Progesterone receptor activation signals behavioral transitions across the reproductive cycle of the female rabbit.

The female rabbit is an exceptional experimental model to define mechanisms by which progesterone (P) controls the expression of reproductive behaviors. In the rabbit, the rise in P levels during pregnancy inhibits estrous scent marking ("chinning"), stimulates the excavation of a nest burrow ("digging"), and primes behaviors later used for nest construction. The pre-parturient fall of P triggers the construction of a straw nest ("straw carrying") that is lined with hair that she pulls from her own body ("hair pulling"). These behaviors can be replicated in ovariectomized (ovx) females given a schedule of estradiol (E) and P that mimics hormone levels during pregnancy (E from days 0 to 4, E + P from days 5 to 17, E from days 18 to 27). We administered PR antagonists RU486 or CDB(VA)2914 to ovx female rabbits during either the initial (days 5-11) or late (days 12-17) phases of P treatment, to determine the role of PR activation in coordinating the expression of these behaviors. Both antiprogestins attenuated the P-mediated decline in chinning and increase in digging when administered during days 5-11. When given across days 12-17, both antiprogestins triggered an early decline in digging, the onset of nest building in some Ss, and the reinstatement of chinning. These results point to a central role of PR activation for establishing and maintaining the behavioral phenotype of pregnancy, and for the behavioral transition from pregnancy to estrus.

Analysis of Variance↗

Reproductive consequences of EDCs in birds: what do laboratory effects mean in field species?

The varied reproductive strategies of birds present a challenge in developing reliable indices for the assessment of effects of endocrine disrupting chemicals (EDCs). Precocial species, such as quail, appear to be most sensitive to EDC effects during embryonic development. Although the Japanese quail (Coturnix japonica) is a nonnative lab species, its reproductive strategy is similar to that of many free-ranging species. Because a great deal is known about the reproductive biology of this species and Japanese quail have a short generation time, this species is an ideal candidate for testing EDC effects. In this review, we present data collected in a two-generation design with embryonic exposure to estradiol benzoate (EB). This study was conducted to provide fundamental information for establishing reliable reproductive endpoints associated with estrogenic EDC exposure. Data were collected for a variety of endpoints, which were chosen as measures of reproductive capability and success. These reproductive fitness measures included fertility, hatching success, and offspring viability. Endocrine measures consisted of plasma hormone levels and gonad weight/condition. Neuroendocrine systems, such as the monoamine neurotransmitter systems, regulate hypothalamic gonadotropin releasing hormone (GnRH) and reproductive behavior. Therefore, these variables should potentially be very sensitive indicators. Behavioral measures included reproductive behavior. Results showed that embryonic estradiol exposure affected endocrine and behavioral responses in males and impacted productivity in females. Therefore, quails provide an excellent model to determine fundamental actions of EDCs. The laboratory trials then serve as a basis for the extrapolation of findings of controlled laboratory studies to effects that may be observable in free-ranging species.

Animals↗

Isolation and characterization of opioid peptides in the avian brain.

Neuropeptides are supposed to be implicated in the regulation of hormone as well as nonhormone dependent behavioral processes in birds. Previous immunohistochemical studies have suggested that in birds opioid pentapeptides, Met- and Leu-enkephalins, may be present in the brain including the regions that regulate sex hormone dependent behaviors, such as reproductive behaviors. To determine biochemically the presence of opioid peptides in the avian brain, a study was conducted to isolate these peptides from Japanese quails and zebra finches. Acetic acid extracts of the quail and finch brains were respectively forced through disposable C-18 reversed-phase cartridges, and then the retained material was subjected to the cation-exchange and reversed-phase high performance liquid chromatographic (HPLC) purifications. All of the purified substances showed a single peak on the reversed-phase HPLC and these substances enhanced spontaneous contractions of the avian rectum. The purified bioactive substances were further subjected to amino acid sequence analysis and were characterized as peptides with the following sequences: Tyr-Gly-Gly-Phe-Met, Tyr-Gly-Gly-Phe-Leu, and Tyr-Gly-Gly-Phe-Met-Arg-Phe. These three peptides were identical with opioid pentapeptides, Met- and Leu-enkephalins, and a heptapeptide, Met-enkephalin-Arg6-Phe7, which had been previously isolated from mammalian species. This is the first direct demonstration of the presence of opioid peptides in the avian brain and confirms previous immunohistochemical findings suggesting a functional role for the opioid peptide in neural mechanisms of avian reproductive behavior.

Amino Acid Sequence↗

Roles of estrogen receptor-alpha gene expression in reproduction-related behaviors in female mice.

The role of gene expression of the estrogen receptor-alpha form (ER alpha) in the regulation of female reproductive behavior was investigated in estrogen receptor knockout (ERKO) mice, deficient specifically for the ER alpha, but not the ER beta, gene. Estrogen- or estrogen- plus progesterone-treated gonadectomized ERKO mice did not show any lordosis response. Detailed behavioral analysis revealed that ERKO females were also deficient in sexual behavioral interactions preceding the lordosis response. They were extremely rejective toward attempted mounts by stud male mice, which could not show any intromissions. During resident-intruder aggression tests, gonadally intact ERKO females were more aggressive toward female intruder mice than wild-type (WT) mice. Gonadectomy did not influence the levels of aggressive behavior, and their genotype differences when mice were tested both before and after gonadectomy. However, when mice were tested after gonadectomy for the first time, very few ERKO mice showed aggression. In contrast to aggression, male-type sexual behavior shown by resident mice toward female intruder mice during aggression tests was not different between ERKO and WT mice and was completely abolished after gonadectomy of the resident mice. Finally, it was also found that ERKO females showed greatly reduced levels of parental behavior toward newborn pups placed in their home cage. These changes in parental behavior were not influenced by gonadectomy. ERKO females retrieved significantly fewer numbers of pups with longer latencies compared with wild-type (WT) or heterozygous (HZ) littermates when they were tested as gonadally intact or 20-65 days after gonadectomy. In addition, during parental behavior tests, a significantly higher percentage of ERKO mice exhibited infanticide compared with WT and HZ mice, which rarely showed infanticide. Taken together, these findings suggest that ER alpha gene expression plays a key role in female mice, not only for sexual behavior but also for other interrelated behaviors, such as parental and aggressive behaviors. In addition, persistence of genotype differences in parental and aggressive behavior after gonadectomy indicates that ER alpha activation during neural developmental processes may also be involved in the regulation of these behaviors.

Aggression↗

Behaviorally induced reproductive compromise in women and men.

Behaviors that activate the hypothalamic-pituitary-adrenal (HPA) axis or suppress the hypothalamic-pituitary-thyroidal (HPT) axis can disrupt the hypothalamic-pituitary-gonadal (HPG) axis in women and men. Individuals with functional hypothalamic hypogonadism typically display a combination of behaviors that serve as psychogenic stressors and metabolic challenges. Complete recovery of gonadal function depends upon restoration of the HPA and HPT axes. Hormone replacement strategies have limited benefit, because they do not achieve this objective and they mask deficits that accrue from altered HPA and HPT function. Although fertility can be restored with exogenous administration of gonadotropins or pulsatile gonadoropin-releasing hormone (GnRH), fertility management alone will not permit the HPA and HPT axes to recover. Thus, for complete recovery to ensue, biopsychosocial interventions that address the individual's unique set of psychogenic factors and metabolic challenges must be devised.

Adult↗

Behavior and reproductive performance by stalled breeding females on a commercial swine farm.

The behavior of stalled females pigs was observed to investigate the relations between behavior and reproductive performance. A commercial farrow-to-finish farm equipped with a computerized recording system with approximately 300 female pig inventories was visited three times to observe three postural behaviors (lying, standing, and sitting) and three stereotypies (vacuum chewing, drinker playing, and bar biting) of stalled females at 15-min intervals for 6 h (25 times including 0 min of one zero-time sampling) after feeding. Relative frequencies (%) of the postural behaviors and the stereotypies for 6 h were expressed as a percentage of a total of 25 time observations. Statistical models for reproductive performance included each behavior, parity, and day of visit. Among 609 pregnant females observed at our three visits, the means in relative frequencies (%) of lying, standing, sitting, vacuum chewing, drinker playing, and bar biting for 6 h were 60.1 +/- 0.91, 32.3 +/- 0.87, 7.60 +/- 0.44, 12.7 +/- 0.65, 0.4 +/- 0.06, and 0.2 +/- 0.50%, respectively. Among 514 farrowed females of the 609 pregnant females, the means of total pigs born, pigs born alive, pigs born dead, birth litter weights, pigs weaned, and adjusted 21-d litter weights were 12.3 +/- 0.13, 11.2 +/- 0.12, 1.1 +/- 0.06, 17.1 +/- 0.18 kg, 10.3 +/- 0.08, and 68.1 +/- 0.40 kg, respectively. Females showing a high relative frequency (> or = 36%) of vacuum chewing during gestation produced fewer (P < 0.05) total pigs born (11.7 +/- 0.38 vs. 12.6 +/- 0.22) than those showing no vacuum chewing. No relationships were found between vacuum chewing and other performance measurements such as pigs born alive, pigs weaned, and adjusted 21-d litter weights. Neither postural behavior nor the other stereotypies were related to reproductive performance. The farrowing rate was not related to any postural behavior and stereotypy in logistic regression mixed models. This study suggests that a subpopulation of females exists on commercial farms that frequently exhibit vacuum chewing and give birth to fewer total pigs. High frequency of vacuum chewing in those females may be indicative of their suboptimal reproductive performance.

Animal Husbandry↗

Social network influences on reproductive health behaviors in urban northern Thailand.

Prevention approaches for reproductive health have evolved from an emphasis on individually focused models of behavior change to a recognition that risk reduction occurs within a context of social norms. Prevention programs can be improved by understanding how social structure influences sexual behavior and using that understanding to develop strategies for positive change. In a dynamic, urban context, communities are better conceptualized as informal networks of ties. These network structures may help to protect, or conversely, expose members to reproductive risk behaviors. Using data from a study of social and sexual networks conducted in northern Thailand, this article describes partner relations and social structure in the modern, urban context, and illustrates the links between individual, relational and structural properties and reproductive risk behaviors. Triangulation of ethnographic, survey and social network data collection and analytic tools provide an opportunity to interpret individual behaviors, meanings of relationships and structural properties of networks. Intervention approaches should build on existing networks, and address the complex meanings of romantic and sexual partnerships.

Community Networks↗