Microevolution of neuroendocrine mechanisms regulating reproductive timing in Peromyscus leucopus

A key question in the evolution of life history and in evolutionary physiology asks how reproductive and other life-history traits evolve. Genetic variation in reproductive control systems may exist in many elements of the complex inputs that can affect the hypothalamic-pituitary-gonadal (HPG) or reproductive axis. Such variation could include numbers and other traits of secretory cells, the amount and pattern of chemical message released, transport and clearance mechanisms, and the number and other traits of receptor cells. Selection lines created from a natural population of white-footed mice (Peromyscus leucopus) that contains substantial genetic variation in reproductive inhibition in response to short winter daylength (SD) have been used to examine neuroendocrine variation in reproductive timing. We hypothesized that natural genetic variation would be most likely to occur in the inputs to GnRH neurons and/or in GnRH neurons themselves, but not in elements of the photoperiodic pathway that would have pleiotropic effects on nonreproductive functions as well as on reproductive functions. Significant genetic variation has been found in the GnRH neuronal system. The number of GnRH neurons immunoreactive to an antibody to mature GnRH peptide under conditions maximizing detection of stained neurons was significantly heritable in an unselected control (C) line. Furthermore, a selection line that suppresses reproduction in SD (photoperiod responsive, R) had fewer IR-GnRH neurons than a selection line that maintains reproduction in SD (photoperiod nonresponsive, NR). This supports the hypothesis that genetic variation in characteristics of GnRH neurons themselves may be responsible for the observed phenotypic variation in reproduction in SD. The R and NR lines differ genetically in food intake and iodo-melatonin receptor binding, as well as in other characteristics. The latter findings are consistent with the hypothesis that genetic variation occurs in the nutritional and hormonal inputs to GnRH neurons. Genetic variation also exists in the phenotypic plasticity of responses to two combinations of treatments, (1) food and photoperiod, and (2) photoperiod and age, indicating genetic variation in individual norms of reaction within this population. Overall, the apparent multiple sources of genetic variation within this population suggest that there may be multiple alternative combinations of alleles for both the R and NR phenotypes. If that interpretation is correct, we suggest that this offers some support for the evolutionary "potential" hypothesis and is inconsistent with the evolutionary "constraint" and "symmorphosis" hypotheses for the evolution of complex neuroendocrine pathways.     

Effects of gonadal steroids on agonistic behavior of female Peromyscus leucopus

The role of gonadal hormones in modifying agonistic behavior of female P. leucopus was examined by means of ovariectomy and treatment with estradiol benzoate (EB), progesterone (P), or testosterone propionate (TP). Aggression was lower in diestrous females than in proestrous females, and was eliminated by ovariectomy. Submissive behavior increased following ovariectomy; surgery had no effect on investigative behavior. Administration of EB had no effect on aggressive or submissive behavior, but higher dosages caused an increase in investigative and sexual behavior. Higher dosages of P increased aggression; P had no effect on submissive or investigative behavior. An increase in aggression also resulted from administration of high levels of TP. TP also caused an increase in investigative behavior, and had no effect on submissive behavior. These results may be due to direct effects of the administered hormones on behavior or to indirect effects such as a stimulation of prolactin secretion or alteration of adrenal function.     

Characteristics of a genetic polymorphism for reproductive photoresponsiveness in the white-footed mouse (Peromyscus leucopus)

Wild populations of Peromyscus are often composed of individuals that vary greatly in their reproductive response to photoperiod. A population of white-footed mice (P. leucopus) from Michigan (43 degrees N) was subjected to mass selection in the laboratory both for and against reproductive photoresponsiveness for four generations. The first generation of selection yielded one line of mice in which about 80% of the individuals were classified as reproductively photoresponsive (i.e., with undeveloped reproductive tracts when reared in short days, 8L: 16D) and another in which only about 20% were reproductively photoresponsive. Some and perhaps most of this difference was accounted for by changes in degree of responsiveness to photoperiod rather than by alterations in the proportion of discrete responsive vs. unresponsive phenotypes. Alteration of critical day length was not a factor. Three more generations of selection failed to change the proportions noted above significantly. Although the genetic control of reproductive photoresponsiveness is undoubtedly complex, a single variable locus may be responsible for much of the heritable variation present in this population. These results also suggest that natural populations contain genetically determined phenotypes that are intermediate between absolutely photoresponsive and absolutely unresponsive. The factors that might promote maintenance of heterogeneity of reproductive photoresponsiveness in a wild population of rodents are considered.     

Social environment modulates photoperiodic immune and reproductive responses in adult male white-footed mice (Peromyscus leucopus)

Social cues may interact with photoperiod to regulate seasonal adaptations in photoperiod-responsive rodents. Specifically, photoperiod-induced adjustments (e.g., reproduction and immune function) may differ among individuals in heterosexual pairs, same-sex pairs, or isolation. Heterosexual cues may be more influential, based on their potential fitness value, than same-sex cues or no social cues. The present study examined the effects of pair (with a male or female) or individual housing on reproductive and immune responses in male white-footed mice (Peromyscus leucopus) maintained in long or short photoperiods. Female pairing did not affect reproductive responses in short-day males. In long days, however, the presence of a female increased both testosterone concentrations and testes mass compared with individually housed and male-paired mice, respectively. Short-day, individually housed males enhanced delayed-type hypersensitivity (DTH) responses compared with single-housed mice in long days, but all paired groups decreased DTH responses regardless of photoperiod. The lack of enhanced DTH response in male mice paired with females coincided with reduced circulating corticosterone concentrations in both photoperiod treatments. Together, these results suggest that social environment may have important modulatory effects on photoperiod-regulated immune responses in male white-footed mice.     

Relative success of residents and immigrants in Peromyscus leucopus

The relative success of a sample of 99 immigrant dispersers was studied in a population of Peromyscus leucopus in deciduous forest from 1980 to 1985. Dispersers were identified in two ways; (1) as immigrants to a natural dispersal sink and (2) as individuals that relocated their center of activity more than one home range diameter within a large live-trapping system. Female immigrants were significantly less likely to be pregnant or lactating than philopatric residents; males showed no significant difference. Reproductive immigrants were more likely than non-reproductive immigrants to establish residency after dispersal. There was no difference in survivorship of philopatrie residents and those dispersers that successfully immigrated.     

Isolation of Borrelia burgdorferi from Peromyscus leucopus in Oklahoma.

Borrelia burgdorferi was isolated from a field-caught Peromyscus leucopus from central Oklahoma (USA). The strain was identified as B. burgdorferi by reaction with monoclonal antibody H5332 specific for the outer surface protein OspA of B. burgdorferi. This represents the first isolation of B. burgdorferi from a wild mouse outside of the normal range of the known vectors Ixodes dammini and I. pacificus.     

Effects of grouping and fighting on the reproductive tracts of male white-footed mice (Peromyscus leucopus)

Summary Adult, male white-footed mice (Peromyscus leucopus) were subjected to a variety of social situations ranging from isolation during the 20 day experimental period to constant contact with both females and other adult males. Contacts included grouping (three or four males per cage) and exposure to fighters (once daily for 20 minutes). The following measurements were recorded: weights of the body, testes, epididymides, vesicular glands, vesicular gland tissue (wet and dry), seminal fluid of the vesicular gland, adrenal glands, and baculum; spermatozoan reserves of the testes and epididymides. Grouping significantly affected both the weight and spermatozoan reserves of the testes and epididymides, as well as both the tissue and seminal fluid weight of the vesicular glands. The results suggested a graded effect of all treatments on the reproductive tract. In order of magnitude of the associated response, from none to greatest, the treatments may be ranked as follows: pairing with females, isolating, handling, fighting, and grouping. All reproductive parameters measured showed this general ranking, suggesting that the response to the various treatments was similar and differed only quantitatively. The results further suggested decreased secretion of LH and testosterone, although measurements of testosterone did not substantiate this conclusion. The lack of significant effects of grouping on adrenal gland weights strengthened the argument that adrenal involvement is not a necessary adjunct to the suppression of the reproductive tract in groupedPeromyscus, but the adrenal may be involved if contacts between males result in overt fighting.     

Dichlorvos toxicity in the white-footed mouse (Peromyscus leucopus)

The organophosphate pesticide, dichlorvos (DDVP), is used commonly to control ectoparasites in laboratory rodents colonies. This compound is relatively nontoxic to Mus musculus at dosages several times the therapeutic level. However, usage of a similar therapeutic level in the white-footed mouse (Peromyscus leucopus) resulted in substantial mortality. To determine whether P. leucopus is more susceptible than M. musculus to the toxic effects of DDVP, both species were exposed to 0, 3 and 6 g of pelleted DDVP per cage. In a subsequent experiment, P. leucopus were exposed to 0 and 1 g of DDVP per cage. Mortality was not observed in M. musculus at any dosage level. P. leucopus exposed to 1, 3 and 6 g of DDVP exhibited mortalities of 3%, 20% and 53%, respectively. Mean serum cholinesterase in P. leucopus exposed to 3 and 6 g of DDVP was 0.35 and 0.21 U/ml as compared to 3.13 U/ml in unexposed mice. The analogous values for M. musculus were 1.60 and 0.79 U/ml while the level in unexposed mice was 6.79 U/ml. In the second experiment, mean serum cholinesterase in P. leucopus exposed to 1 g of DDVP was 0.32 U/ml as compared to 2.33 U/ml in unexposed mice. Histopathology revealed no lesions in the brain, liver or kidneys. The increased susceptibility of P. leucopus to the toxic effects of DDVP was related to the lowered serum cholinesterase. This indicates that DDVP should not be used for control of ectoparasites in P. leucopus.     

Phenotypic plasticity of reproductive traits in response to food availability and photoperiod in white-footed mice (Peromyscus leucopus)

Changes in photoperiod, ambient temperature and food availability trigger seasonal acclimatization in physiology and behavior of many animals. In the present study, seasonal adjustments in body mass and in several physiological, hormonal, and biochemical markers were examined in wild-captured plateau pikas (Ochotona curzoniae) from the Qinghai-Tibetan plateau. Our results showed that plateau pikas maintained a relatively constant body mass throughout the year and showed no seasonal changes in body fat mass and circulating levels of serum leptin. However, nonshivering thermogenesis, cytochrome c oxidase activity, and mitochondrial uncoupling protein 1 (UCP1) contents in brown adipose tissues were significantly enhanced in winter. Further, serum leptin levels were positively correlated with body mass and body fat mass while negatively correlated with UCP1 contents. Together, these data suggest that plateau pikas mainly depend on increasing thermogenic capacities, rather than decreasing body mass, to cope with cold, and leptin may play a potential role in their thermogenesis and body mass regulation.     

Major histocompatibility complex class I genes of Peromyscus leucopus

Class I genes of the Peromyscus leucopus major histocompatibility complex (MhcPele) were examined by Southern blot hybridization, genomic cloning, and DNA sequencing. At least three distinct subtypes of Pele class I genes were discerned, which we have designated Pele-A, B, and C. The nucleotide sequences of exon 5-containing regions (encoding the transmembrane domain) suggested that Pele-A genes are homologs of mouse H-2K, D, L, and Q genes and that Pele-B genes correspond to mouse Tla genes. The Pele-C genes appeared similar to mouse M1 genes. The number of unique genes in each subtype cloned from an individual P. leucopus were 20 for Pele-A, 13 for Pele-B, and 2 for Pele-C. Three genomic clones showed cross-hybridization to both Pele-A and Pele-B gene-specific probes. Six genomic clones remained unclassified as they did not cross-hybridize to exon 5-containing probes from Pele-A, B, or C genes. The homology between the transmembrane domains of Pele class I gene subtypes was found to be similar to that observed between the transmembrane domains of H-2 subtypes (or groups). Interspecific similarity of exon 5 was found to be 81%–88% between Pele class I genes and their H-2 counterparts.The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession numbers M33983-5.     

Early-summer inhibition of reproduction in wild white-footed mice (Peromyscus leucopus noveboracensis): influence of supplemental food

Adults of wild white-footed mouse (Peromyscus leucopus noveboracensis) populations in southeastern Virginia have been shown to be reproductively suppressed during May–July compared with other months of the reproductive season. The gonads and sex accessory glands are also significantly smaller during May–July than at other times of the year. The causes of this early summer reproductive suppression are unknown. In this study, food (Agway 3000) that could not be hoarded was supplied in feeding stations on one-half the 11-ha wooded study area during 1990 and 1991. Food consumption (g) was positively but not significantly correlated with population density (adults/ha) during both years. Population density was higher during 1991 on the food-supplemented area than on the nonsupplemented area, but the statistical significance was marginal. Mice of both sexes living on both areas during 1990 and 1991 exhibited significant reproductive suppression during May–June. Further, mice of both sexes living on both areas during both years had significantly smaller gonads and sex accessory glands during May–June compared with other months of the year. Thus, during both years, surplus food did not prevent suppression of reproductive function in this wild population, and this phenomenon remains unexplained. Received: November 4, 1998 / Accepted: October 5, 1999