Genome-wide analysis identifies 12 loci influencing human reproductive behavior.

The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits

Novel unconditioned prosocial behavior in prairie voles (Microtus ochrogaster) as a model for empathy

Abstract Objective In this study, empathy is quantified using a novel social test. Empathy and prosocial behavior are linked to the expression of oxytocin in humans and rodent models. Specifically, prosocial behavior in prairie voles (Microtus ochrogaster) has been linked to the expression of oxytocin in the paraventricular nucleus of the hypothalamus. The animal’s behavior was considered empathic if it spends significantly more time attempting to remove a loos fitting restraint (tether) from the stimulus animal than time in contact with a, simultaneously presented, non-social object similar to the tether. The behavioral data was cross-referenced with the number of neurons expressing oxytocin and arginine vasopressin, as well as the density of dopaminergic neurons (identified by the expression of tyrosine hydroxylase), in the paraventricular nucleus of the hypothalamus. These proteins influence empathic behavior in humans, non-human primates, rats, mice, and prairie voles. Results The consistency between neuroanatomical mechanisms linked to empathy, and the durations of time spent engaging in empathic contact, support the prediction that the empathic contact in this test is a distinct prosocial behavior, lacking prior behavioral training or the naturally occurring ethological relevance of other prosocial behaviors, and is a measure of empathy

A Novel Model for Neuroendocrine Toxicology: Neurobehavioral Effects of BPA Exposure in a Prosocial Species, the Prairie Vole (Microtus ochrogaster)

Impacts on brain and behavior have been reported in laboratory rodents after developmental exposure to bisphenol A (BPA), raising concerns about possible human effects. Epidemiological data suggest links between prenatal BPA exposure and altered affective behaviors in children, but potential mechanisms are unclear. Disruption of mesolimbic oxytocin (OT)/vasopressin (AVP) pathways have been proposed, but supporting evidence is minimal. To address these data gaps, we employed a novel animal model for neuroendocrine toxicology: the prairie vole (Microtus ochrogaster), which are more prosocial than lab rats or mice. Male and female prairie vole pups were orally exposed to 5-μg/kg body weight (bw)/d, 50-μg/kg bw/d, or 50-mg/kg bw/d BPA or vehicle over postnatal days 8–14. Subjects were tested as juveniles in open field and novel social tests and for partner preference as adults. Brains were then collected and assessed for immunoreactive (ir) tyrosine hydroxylase (TH) (a dopamine marker) neurons in the principal bed nucleus of the stria terminalis (pBNST) and TH-ir, OT-ir, and AVP-ir neurons in the paraventricular nucleus of the hypothalamus (PVN). Female open field activity indicated hyperactivity at the lowest dose and anxiety at the highest dose. Effects on social interactions were also observed, and partner preference formation was mildly inhibited at all dose levels. BPA masculinized principal bed nucleus of the stria terminalis TH-ir neuron numbers in females. Additionally, 50-mg/kg bw BPA-exposed females had more AVP-ir neurons in the anterior PVN and fewer OT-ir neurons in the posterior PVN. At the 2 lowest doses, BPA eliminated sex differences in PVN TH-ir neuron numbers and reversed this sex difference at the highest dose. Minimal behavioral effects were observed in BPA-exposed males. These data support the hypothesis that BPA alters affective behaviors, potentially via disruption of OT/AVP pathways

Anxiogenic Effects of Developmental Bisphenol A Exposure Are Associated with Gene Expression Changes in the Juvenile Rat Amygdala and Mitigated by Soy

<div><p>Early life exposure to Bisphenol A (BPA), a component of polycarbonate plastics and epoxy resins, alters sociosexual behavior in numerous species including humans. The present study focused on the ontogeny of these behavioral effects beginning in adolescence and assessed the underlying molecular changes in the amygdala. We also explored the mitigating potential of a soy-rich diet on these endpoints. Wistar rats were exposed to BPA via drinking water (1 mg/L) from gestation through puberty, and reared on a soy-based or soy-free diet. A group exposed to ethinyl estradiol (50 µg/L) and a soy-free diet was used as a positive estrogenic control. Animals were tested as juveniles or adults for anxiety-like and exploratory behavior. Assessment of serum BPA and genistein (GEN), a soy phytoestrogen, confirmed that internal dose was within a human-relevant range. BPA induced anxiogenic behavior in juveniles and loss of sexual dimorphisms in adult exploratory behavior, but only in the animals reared on the soy-free diet. Expression analysis revealed a suite of genes, including a subset known to mediate sociosexual behavior, associated with BPA-induced juvenile anxiety. Notably, expression of estrogen receptor beta (<em>Esr2</em>) and two melanocortin receptors (<em>Mc3r</em>, <em>Mc4r</em>) were downregulated. Collectively, these results show that behavioral impacts of BPA can manifest during adolescence, but wane in adulthood, and may be mitigated by diet. These data also reveal that, because ERβ and melanocortin receptors are crucial to their function, oxytocin/vasopressin signaling pathways, which have previously been linked to human affective disorders, may underlie these behavioral outcomes.</p> </div

BPA, EE and dietary effects on juvenile Elevated Plus Maze (EPM) activity.

<p>(A) BPA exposure significantly decreased the percent of males that entered an open arm. No significant effect of gender was found for any subsequent measure, therefore the data were collapsed across sexes. (B) There were no significant group differences in latency to enter the open arms. (C) A main effect of diet on mean number of open arm entries was identified (not depicted), with soy-fed animals making significantly more entries. BPA exposed animals on the soy-free diet (BPA) made fewer entries compared to the diet matched controls (Soy-free) and also the BPA exposed animals on the soy diet (BPA + Soy). (D) Soy-based diet significantly increased time spent on the open arms, regardless of BPA exposure. EE had no significant effect on any EPM endpoint examined. Graphs depict mean ± SEM, *<i>P</i>≤0.05, **<i>P</i>≤0.001, # main effect of diet; <i>P</i>≤0.05.</p

BPA, EE and dietary effects on adult Elevated Plus Maze (EPM) activity.

<p>As expected, a significant gender effect was found for all measurements except latency to enter an open arm. In general, BPA exposure eliminated these sex differences. (A) A higher percent of females entered the open arms than males regardless of exposure group. (B) Soy-free males took significantly longer to enter an open arm than females maintained on the same diet. BPA exposure eliminated this sex difference, with a tendency for reversal. Soy diet also eliminated this behavioral sex difference. (C) Females made significantly more open arm entries than males in all groups except those on the soy-free diet and exposed to BPA (BPA). There was no overall effect of BPA or diet on this behavior. (D) Similarly, in all groups except those on the soy-free diet and exposed to BPA, females spent significantly more time on the open arms than males. Graphs depict mean ± SEM, *<i>P</i>≤0.05, ** <i>P</i>≤0.001.</p

Mean Pup Intake (ml) and Exposure Levels (µg) of BPA or EE.

<p>Average daily water consumption was quantified from the pups during postnatal days 21–40, from which average daily BPA or EE was calculated. Soy exposure occurred via diet only and therefore is not included.</p

Mean Dam Fluid Intake (ml) and Exposure Levels (µg) of BPA or EE.

<p>Average daily water consumption was quantified from the dams during mid-gestation and mid-lactation, from which average daily BPA or EE was calculated. Soy exposure occurred via diet only and therefore is not included.</p