Paternal care in rodents: weakening support for hormonal regulation of the transition to behavioral fatherhood in rodent animal models of biparental care

Male rodents that are naturally paternal, like all females, must inhibit infanticide and activate direct parental behavior as they become parents. Males, however, alter their behavior in the absence of parturition, postpartum ovulation and lactation, and therefore do not experience the hormone dynamics associated with such conditions. Paternal males might nevertheless use the same hormones to activate pre-existing maternal behavior pathways in the brain. Positive and inverse associations between prolactin, sex steroids (estradiol, testosterone, progesterone), glucocorticoids, oxytocin and vasopressin and paternal behavior are reviewed. Across biparental rodents (Phodopus campbelli, Peromyscus californicus, Microtus ochrogaster, and Meriones unguiculatus), as well as non-human primates and men, hormone-behavior associations are broadly supported. However, experimental manipulations (largely restricted to P. campbelli) suggest that the co-variation of hormones and paternal behavior is not causal in paternal behavior. Perhaps the hormone-behavior associations shared by P. campbelli and other paternal males are important for other challenges at the same time as fatherhood (e.g., mating during the postpartum estrus). On the other hand, each paternal species might, instead, have unique neuroendocrine pathways to parental behavior. In the latter case, future comparisons might reveal extraordinary plasticity in how the brain forms social bonds and alters behavior in family groups.     

Non-invasive measurement of small peptides in the common marmoset (Callithrix jacchus): a radiolabeled clearance study and endogenous excretion under varying social conditions

A non-invasive assay for measurement of oxytocin (OT) and vasopressin (AVP) in primates would enable researchers to study the relationship between the endocrine system and behavior without disturbing potentially endangered animals in their natural habitats. In order to test whether or not OT specifically would be measurable in the urine of a primate, 10 microCi of tritium-labeled OT were injected into the peripheral blood supply of four adult male common marmosets (Callithrix jacchus), with continuous urinary collection over 48 h. When urine was processed by HPLC separation and beta counting for radioactive clearance, the label was present in all samples in the fraction where OT elutes. Large amounts of OT were also seen in a fraction other than that containing the OT standard, indicating that OT is measurable but that it also undergoes substantial metabolic breakdown. In a second experiment, we isolated six common marmosets for 48 h and then exposed them to social contact to evaluate the effect of changing social stimuli on endogenous urinary measurement of both OT and AVP. Both were measured after HPLC separation to isolate the intact molecule and also to control for cross-reactivity with metabolites in subsequent RIA. Cortisol was also measured to objectively evaluate the stress response. A priori assumptions were that urinary OT and AVP would be lower during a period of isolation and higher during periods of social contact. These assumptions were met, leading us to conclude that peripheral OT and AVP are measurable via urinary assay and that such an assay is a valid means of evaluating social condition in this species.     

Distribution of osmoregulatory peptides and neuronal-glial configuration in the hypothalamic magnocellular nuclei of desert rodents

The desert rodents Psammomys obesus and Gerbillus tarabuli live under extreme conditions and overcome food and water shortage by modes of food and fluid intake specific to each species. Using immunohistochemistry and electron microscopy, we found that the hypothalamic magnocellular nuclei, and in particular, their vasopressinergic component, is highly and similarly developed in Psammomys and Gerbillus. In comparison to other rodents, the hypothalamus in both species contains more magnocellular VP neurons that, together with oxytocin neurons, accumulate in distinct and extensive nuclei. As in dehydrated rodents, many magnocellular neurons contained both neuropeptides. A striking feature of the hypothalamic magnocellular system of Psammomys and Gerbillus was its display of ultrastructural properties related to heightened neurosecretion, namely, a significant reduction in glial coverage of neuronal somata and dendrites in the hypothalamic nuclei. There were many neuronal elements whose surfaces were directly juxtaposed and shared the same synapses. Their magnocellular nuclei also showed a high level of sialylated isoform of the Neural Cell Adhesion Molecule (PSA-NCAM) that underlies their capacity for neuronal and glial plasticity. These species thus offer striking models of structural neuronal and glial plasticity linked to natural conditions of heightened neurosecretion.     

普贝生用于足月妊娠促宫颈成熟的疗效观察

目的：探讨普贝生促进宫颈成熟,提高足月妊娠经阴道分娩的有效性和安全性。方法：120例足月妊娠的未临产孕妇随机分为试验组与对照组,其中试验组50例给予阴道后穹隆置入普贝生1～2次,对照组50例给予小剂量催产素静脉滴注,比较两组宫颈成熟度,分娩情况及对于产妇、新生儿的影响。结果：①试验组宫颈Bishop评分增加3．81±1．04,对照组增加3．09±1．15,两组间差异有统计学意义（P〈0．05）②试验组促宫颈成熟的显效率为78．33％,总有效率为91．67％,高于对照组35．00％显效率和63．33％总有效率（P〈0．01）。③试验组阴道分娩率73．33％,进入产程时间（34．19±13．20）h,产程（8．47±2．68）h,对照组阴道分娩率41．67％,进入产程时间（52．14±16．05）h,产程（12．25±3．73）h,两组间比较差异有显著性（P〈0．01或0．05）。④试验组产后出血量（225．31±67．80）ml,新生儿体重（3369．48±311．65）g,Apgar评分9．52±0．39,对照组产后出血量（232．44±75．76）ml,新生儿体重（3417．63±359．68）g,Apgar评分9．48±0．47,两组间差异无统计学意义（P〉0．05）。结论：普贝生可有效促进足月妊娠产妇的宫颈成熟．提高经阴道引产成功率,降低剖宫产率,且安全性好,对母儿影响小。     

Enhanced osteoclastogenesis in women after natural delivery

In the pre-expulsive and expulsive phases of labor, oxytocin and several other osteoclastogenic mediators, such as prostaglandins and IL-6, are secreted in high concentrations. This study was undertaken to assess whether the peripheral blood obtained from healthy women after vaginal delivery contains a larger pool of osteoclast precursors compared with age- and gender-matched controls. Our results clearly show that the number and size of osteoclasts generated in vitro from osteoclast precursors isolated from women after delivery are significantly larger than those from controls. This finding can account for the decrease in bone mass that is often observed during the breastfeeding period and the concomitant release of high quantities of calcium in the milk. Further investigations are required to establish whether analysis of blood osteoclast precursors can be predictive of changes in bone remodeling in this setting.     

The vertebrate social behavior network: evolutionary themes and variations

Based on a wide variety of data, it is now clear that birds and teleost (bony) fish possess a core "social behavior network" within the basal forebrain and midbrain that is homologous to the social behavior network of mammals. The nodes of this network are reciprocally connected, contain receptors for sex steroid hormones, and are involved in multiple forms of social behavior. Other hodological features and neuropeptide distributions are likewise very similar across taxa. This evolutionary conservation represents a boon for experiments on phenotypic behavioral variation, as the extraordinary social diversity of teleost fish and songbirds can now be used to generate broadly relevant insights into issues of brain function that are not particularly tractable in other vertebrate groups. Two such lines of research are presented here, each of which addresses functional variation within the network as it relates to divergent patterns of social behavior. In the first set of experiments, we have used a sexually polymorphic fish to demonstrate that natural selection can operate independently on hypothalamic neuroendocrine functions that are relevant for (1) gonadal regulation and (2) sex-typical behavioral modulation. In the second set of experiments, we have exploited the diversity of avian social organizations and ecologies to isolate species-typical group size as a quasi-independent variable. These experiments have shown that specific areas and peptidergic components of the social behavior network possess functional properties that evolve in parallel with divergence and convergence in sociality.     

Reduced anxiety in postpartum rats requires recent physical interactions with pups, but is independent of suckling and peripheral sources of hormones

Changes in emotional behavior occur across the reproductive cycle in female rodents, with reduced anxiety found during the postpartum period, but relatively little is known about factors contributing to this decreased anxiety. Using increased duration of time spent in the open arms of an elevated plus-maze as an indicator of reduced anxiety, it was found in a series of experiments that (1) anxiety is significantly reduced in Long-Evans females during the first week of lactation, but not thereafter, (2) relatively recent contact with pups before testing (within 4 h) is necessary for their reduced anxiety, (3) dams that receive only distal sensory cues from pups for the 4 h prior to testing do not show reduced anxiety, (4) the absence of nipples, and therefore a lack of suckling by pups, has no effect on dams' anxiety, (5) cesarean delivery of pups 2 days prior to expected parturition did not alter later anxiety in dams, (6) hypophysectomy during mid-pregnancy or ovariectomy within 24 h after parturition also did not prevent reduced anxiety in dams, and (7) differences in anxiety between lactating and virgin females are greatest 4-8 min after being placed in the plus-maze. Therefore, exposure to their own peripheral hormones through mid-pregnancy is sufficient to prime female rats to show reduced anxiety, but only if they later have recent physical interaction with pups. Furthermore, because suckling and the peripheral hormones released during suckling appear to be unnecessary, decreased anxiety in maternal rats may instead be regulated by the transient intracerebral release of neuropeptides or neurotransmitters while dams receive other types of tactile inputs from their infants.     

Both oxytocin and vasopressin may influence alloparental behavior in male prairie voles

Neuropeptides, especially oxytocin (OT) and arginine vasopressin (AVP), have been implicated in several features of monogamy including alloparenting. The purpose of the present study was to examine the role of OT and AVP in alloparental behavior in reproductively na?ve male prairie voles. Males received intracerebroventricular (ICV) injections of artificial cerebrospinal fluid (aCSF), OT, an OT receptor antagonist (OTA), AVP, an AVP receptor antagonist (AVPA), or combinations of OTA and AVPA and were subsequently tested for parental behavior. Approximately 45 min after treatment, animals were tested for behavioral responses to stimulus pups. In a 10-min test, spontaneous alloparental behavior was high in control animals. OT and AVP did not significantly increase the number of males that showed parental behavior, although more subtle behavioral changes were observed. Combined treatment with AVPA and OTA (10 ng each) significantly reduced male parental behavior and increased attacks; following a lower dose (1 ng OTA/1 ng AVPA), males were less likely to display kyphosis and tended to be slower to approach pups than controls. Since treatment with only one antagonist did not interfere with the expression of alloparenting, these results suggest that access to either OT or AVP receptors may be sufficient for the expression of alloparenting.     

Olfactory-mediated parasite recognition and avoidance: linking genes to behavior

A major cost of social behavior is the increased risk of exposure to parasites and infection. Animals utilize social information, including chemical signals, to recognize and avoid conspecifics infected with either endoparasites or ectoparasites. Here, we briefly discuss the relations among odors, parasite recognition, and avoidance, and consider some of the associated hormonal, neural, and genomic mechanisms. In rodents, odor cues mediate sexual and competitive interactions and are of major importance in individual recognition and mate detection and choice. Female mice distinguish between infected and uninfected males by urinary odors, displaying aversive response to, and avoidance of, the odors of infected individuals. This reduces both the likelihood of the transmission of parasites to themselves and allows females to select for parasite-free males. This set of olfactory and mate choice responses can be further modulated by social factors such as previous experience and exposure to infected males and the mate choices of other females. Male mice, who also face the threat of infection, similarly distinguish and avoid parasitized individuals by odor, thus reducing their likelihood of infection. This recognition and avoidance of the odors of infected individuals involves genes for the neuropeptide, oxytocin (OT), and estrogenic mechanisms. Mice with deletions of the oxytocin gene [OT knockout mice (OTKO)] and mice whose genes for estrogen receptor (ER)-alpha or ER-beta have been disrupted [ER knockout mice (ERKO), alpha-ERKO and beta-ERKO] are specifically impaired in their recognition of, aversion to, and memory of the odors of infected individuals. These findings reveal some of the genes involved in the mediation of social recognition in the ecologically relevant context of parasite recognition and avoidance.     

ADAMs, a disintegrin and metalloproteinases, mediate shedding of oxytocinase

Placental leucine aminopeptidase (P-LAP), a type-II transmembrane protease responsible for oxytocin degradation during pregnancy, is converted to a soluble form through proteolytic cleavage. The goal of this study was to determine the nature of the P-LAP secretase activity. The hydroxamic acid-based metalloprotease inhibitors GM6001 and ONO-4817 as well as the TNF-alpha protease inhibitor-2 (TAPI-2) reduced P-LAP release, while tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2, which are matrix metalloproteinase inhibitors, had no effect on P-LAP release in Chinese hamster ovary (CHO) cells stably overexpressing P-LAP, thus indicating possible involvement of ADAM (a disintegrin and metalloproteinase) members in P-LAP shedding. Furthermore, overexpression of ADAM9 and ADAM12 increased P-LAP release in P-LAP-CHO transfectants. Immunohistochemical analysis in human placenta demonstrated strong expression of ADAM12 in syncytiotrophoblasts, while little expression of ADAM9 was detected throughout the placenta. Our results suggest ADAM members, at least including ADAM12, are involved in P-LAP shedding in human placenta.