Beyond a "woman's problem" : the role of relationship processes in female genital pain

Female genital pain is a prevalent condition that can disrupt the psychosexual and relational well-being of affected women and their romantic partners. Despite the intimate context in which the pain can be elicited (i.e., during sexual intercourse), interpersonal correlates of genital pain and sexuality have not been widely studied in comparison to other psychosocial factors. This review describes several prevailing theoretical models explaining the role of the partner in female genital pain: the operant learning model, cognitive-behavioral and communal coping models, and intimacy models. The review includes a discussion of empirical research on the interpersonal and partner correlates of female genital pain and the impact of genital pain on partners’ psychosexual adjustment. Together, this research highlights a potential reciprocal interaction between both partners’ experiences of female genital pain. The direction of future theoretical, methodological, and clinical research is discussed with regard to the potential to enhance understanding of the highly interpersonal context of female genital pain

Influence of mutations affecting gonadotropin production or responsiveness on expression of inhibin subunit mRNA and protein in the mouse ovary

Measurement of inhibins A and B in the serum of normal cyclic rodents has implicated FSH in the regulation of these peptides within the ovary. To extend these observations we have used a panel of mutant mice carrying mutations which affect either the production of, or the ability to respond to, FSH and LH. As a consequence, the females are infertile and show different degrees of follicular development. The aim of this study was to measure inhibin gene transcription in the ovaries of these mutant females together with inhibin protein levels in ovaries and serum and to relate these to follicular development within the ovary. Comparison was made with a pool of normal/heterozygous females. In hpg females where lack of GnRH production results in the absence of gonadotropin synthesis, in FSHbeta knockout (FSHbetaKO) females where disruption of the gene encoding FSHbeta results in the absence of FSH production, and in FSH receptor knockout (FSHRKO) females which are unable to respond to circulating FSH, follicular development remains at the pre-antral stage in these three mutants. Only in the hpg females were common inhibin alpha subunit mRNA levels significantly lower than normal. In these three mutants, however, mRNA levels for both the betaA and betaB subunits were extremely low compared with normal mice. At the protein level, neither inhibin A nor B was detected in the serum of these three mutants; however inhibin B, albeit at very low levels, was detectable within the ovaries. These observations confirm a major role for FSH in the control of transcription of the RA and betaB genes but suggest that the constitutive transcription of the alpha subunit is less dependent on FSH. In contrast, in LH receptor knockout (LuRKO) female mice inhibin betaA subunit mRNA levels were similar to those measured in normal/heterozygous females but levels of inhibin alpha and betaB subunit mRNAs were significantly higher than in the normal group. This was reflected in significantly higher inhibin B protein levels in ovaries and serum. An inability to respond to LH combined with high circulating levels of FSH leads to a high proportion of antral follicles in LuRKO females, with granulosa cells constituting the major cell type within the ovary. The high percentage of antral granulosa cells is likely to account for the significantly higher levels of inhibin B production in these ovaries.

Ethnic differences in beta-cell function, dietary intake and expression of the metabolic syndrome among UK adults of south Asian, black African-Caribbean and white-European origin at high risk of metabolic syndrome

A cross-sectional analysis of ethnic differences in dietary intake, insulin sensitivity and beta-cell function, using the intravenous glucose tolerance test (IVGTT), was conducted on 497 healthy adult participants of the ‘Reading, Imperial, Surrey, Cambridge, and Kings’ (RISCK) study. Insulin sensitivity (Si) was significantly lower in African-Caribbean (AC) and South Asian (SA) participants [IVGTT-Si; AC: 2.13 vs SA: 2.25 vs white-European (WE): 2.84 (×10−4 mL µU min)2, p < 0.001]. AC participants had a higher prevalence of anti-hypertensive therapy (AC: 19.7% vs SA: 7.5%), the most cardioprotective lipid profile [total:high-density lipoprotein (HDL); AC: 3.52 vs SA: 4.08 vs WE: 3.83, p = 0.03] and more pronounced hyperinsulinaemia [IVGTT–acute insulin response (AIR)] [AC: 575 vs SA: 428 vs WE: 344 mL/µU/min)2, p = 0.002], specifically in female participants. Intake of saturated fat and carbohydrate was lower and higher in AC (10.9% and 50.4%) and SA (11.1% and 52.3%), respectively, compared to WE (13.6% and 43.8%, p < 0.001). Insulin resistance in ACs is characterised by ‘normal’ lipid profiles but high rates of hypertension and pronounced hyperinsulinaemia.

Female-specific intergenerational transmission patterns of the human corticolimbic circuitry

Parents have large genetic and environmental influences on offspring’s cognition, behavior, and brain. These intergenerational effects are observed in mood disorders, with particularly robust association in depression between mothers and daughters. No studies have thus far examined the neural bases of these intergenerational effects in humans. Corticolimbic circuitry is known to be highly relevant in a wide range of processes including mood regulation and depression. These findings suggest that corticolimbic circuitry may also show matrilineal transmission patterns. We therefore examined human parent-offspring association in this neurocircuitry, and investigated the degree of association in gray matter volume between parent and offspring. We used voxel-wise correlation analysis in a total of 35 healthy families, consisting of parents and their biological offspring. We found positive associations of regional grey matter volume in the corticolimbic circuit including the amygdala, hippocampus, anterior cingulate cortex, and ventromedial prefrontal cortex between biological mothers and daughters. This association was significantly greater than mother-son, father-daughter, and father-son associations. The current study suggests that the corticolimbic circuitry, which has been implicated in mood regulation, shows a matrilineal specific transmission patterns. Our preliminary findings are consistent with what has been found behaviorally in depression, and may have clinical implications for disorders known to have dysfunction in mood regulation such as depression. Studies such as ours will likely bridge animal work examining gene expression in the brains and clinical symptom-based observations, and provide promising ways to investigate intergenerational transmission patterns in the human brain.

Activation of the GPR30 receptor promotes lordosis in female mice

BACKGROUND/AIMS: Estrogens are important effectors of reproduction and are critical for upregulating female reproductive behavior or lordosis in females. In addition to the importance of transcriptional regulation of genes by 17beta-estradiol-bound estrogen receptors (ER), extranuclear signal transduction cascades such as protein kinase A (PKA) are also important in regulating female sexual receptivity. GPR30 (G-protein coupled receptor 30), also known as GPER1, a putative membrane ER (mER), is a G protein-coupled receptor that binds 17beta-estradiol with an affinity that is similar to that possessed by the classical nuclear ER and activates both PKA and extracellular-regulated kinase signaling pathways. The high expression of GPR30 in the ventromedial hypothalamus, a region important for lordosis behavior as well as kinase cascades activated by this receptor, led us to hypothesize that GPR30 may regulate lordosis behavior in female rodents. METHOD: In this study, we investigated the ability of G-1, a selective agonist of GPR30, to regulate lordosis in the female mouse by administering this agent prior to progesterone in an estradiol-progesterone priming paradigm prior to testing with stud males. RESULTS: As expected, 17beta-estradiol benzoate (EB), but not sesame oil, increased lordosis behavior in female mice. G-1 also increased lordosis behavior in female mice and decreased the number of rejective responses towards male mice, similar to the effect of EB. The selective GPR30 antagonist G-15 blocked these effects. CONCLUSION: This study demonstrates that activation of the mER GPR30 stimulates social behavior in a rodent model in a manner similar to EB.

Ovarian-Steroid Modulation of Locus Coeruleus Activity in Female Rats: Involvement in Luteinising Hormone Regulation

The noradrenergic nucleus locus coeruleus (LC) has been reported to regulate luteinising hormone (LH) secretion in female rats. Both oestrogen and progestin receptors have been demonstrated in LC neurones, suggesting that these cells are possibly responsive to variations in circulating levels of ovarian steroids. We therefore evaluated changes in the activity of LC neurones during the oestrous cycle and after ovarian-steroid treatment in ovariectomised (OVX) rats, as determined by immunoreactivity to Fos-related antigens (FRA), which comprises all of the known members of the Fos family. Effects of ovarian steroids on the firing rate of LC neurones were also determined in a slice preparation. The number of FRA/tyrosine hydroxylase (TH)-immunoreactive (ir) neurones in the LC increased from 14.00-16.00 h on pro-oestrus, coinciding with the onset of the LH surge and rise in plasma progesterone. FRA immunoreactivity was unaltered during dioestrus. Oestradiol-treated OVX rats (OVX+E) displayed marked reduction in FRA/TH-ir neurones in LC compared to oil-treated OVX rats. Accordingly, oestradiol superfusion significantly reduced the spontaneous firing rate of LC neurones in slices from OVX rats. Compared to OVX+E, oestradiol-treated rats injected with progesterone at 08.00 h (OVX+EP) exhibited higher number of FRA/TH-ir neurones in the LC at 10.00 h and 16.00 h, and great amplification of the LH surge. Bath application of progesterone significantly increased the spontaneous firing rate of OVX+E LC neurones. Our data suggest that ovarian steroids may physiologically modulate the activity of LC neurones in females, with possible implications for LH secretion. Moreover, oestradiol and progesterone appear to exert opposite and complementary effects (i.e. whereas oestradiol inhibits, progesterone, after oestradiol priming, stimulates LC activity).

Paullinia cupana Mart. var. sorbilis, Guarana, Increases Survival of Ehrlich Ascites Carcinoma (EAC) Bearing Mice by Decreasing Cyclin-D1 Expression and Inducing a G0/G1 Cell Cycle Arrest in EAC Cells

The objective of this work is to report the antiproliferative effect of P. cupana treatment in Ehrlich Ascites Carcinoma (EAC)-bearing animals. Female mice were treated with three doses of powdered P. cupana (100, 1000 and 2000 mg/kg) for 7 days, injected with 10(5) EAC cells and treated up to day 21. In addition, a survival experiment was carried out with the same protocol. P. cupana decreased the ascites volume (p = 0.0120), cell number (p = 0.0004) and hemorrhage (p = 0.0054). This occurred through a G1-phase arrest (p < 0.01) induced by a decreased gene expression of Cyclin D1 in EAC cells. Furthermore, P. cupana significantly increased the survival of EAC-bearing animals (p = 0.0012). In conclusion, the P. cupana growth control effect in this model was correlated with a decreased expression of cyclin D1 and a G1 phase arrest. These results reinforce the cancer therapeutic potential of this Brazilian plant. Copyright (C) 2010 John Wiley & Sons, Ltd.

Messenger RNA expression of Pabpnl1 and Mbd3l2 genes in oocytes and cleavage embryos

Objective: To identify genes specifically expressed in mammalian oocytes using an in silico subtraction, and to characterize the mRNA patterns of selected genes in oocytes, embryos, and adult tissues. Design: Comparison between oocyte groups and between early embryo stages. Setting: Laboratories of embryo manipulation and molecular biology from Departamento de Genetica (FMRP) and Departamento de Ciencias Basicas (FZEA) - University of Sao Paulo. Sample(s): Oocytes were collected from slaughtered cows for measurements, in vitro fertilization, and in vitro embryo culture. Somatic tissue, excluding gonad and uterus tissue, was collected from male and female cattle. Main Outcome Measure(s): Messenger RNA levels of poly(A)-binding protein nuclear-like 1 (Pabpnl1) and methyl-CpG-binding domain protein 3-like 2 (Mbd3l2). Result(s): Pabpnl1 mRNA was found to be expressed in oocytes, and Mbd3l2 transcripts were present in embryos. Quantification of Pabpnl1 transcripts showed no difference in levels between good-and bad-quality oocytes before in vitro maturation (IVM) or between good-quality oocytes before and after IVM. However, Pabpnl1 transcripts were not detected in bad-quality oocytes after IVM. Transcripts of the Mbd3l2 gene were found in 4-cell, 8-cell, and morula-stage embryos, with the highest level observed in 8-cell embryos. Conclusion(s): Pabpnl1 gene expression is restricted to oocytes and Mbd3l2 to embryos. Different Pabpnl1 mRNA levels in oocytes of varying viability suggest an important role in fertility involving the oocyte potential for embryo development. (Fertil Steril (R) 2010; 93: 2507-12. (C) 2010 by American Society for Reproductive Medicine.)

EXPRESSION OF COCAINE- AND AMPHETAMINE-REGULATED TRANSCRIPT IN THE RAT FOREBRAIN DURING POSTNATAL DEVELOPMENT

Cocaine- and amphetamine-regulated transcript (CART) is widespread in the rodent brain. CART has been implicated in many different functions including reward, feeding, stress responses, sensory processing, learning and memory formation. Recent studies have suggested that CART may also play a role in neural development. Therefore, in the present study we compared the distribution pattern and levels of CART mRNA expression in the forebrain of male and female rats at different stages of postnatal development: P06, P26 and P66. At 6 days of age (P06), male and female rats showed increased CART expression in the somatosensory and piriform cortices, indusium griseum, dentate gyrus, nucleus accumbens, and ventral premammillary nucleus. Interestingly, we found a striking expression of CART mRNA in the ventral posteromedial and ventral posterolateral thalamic nuclei. This thalamic expression was absent at P26 and P66. Contrastingly, at P06 CART mRNA expression was decreased in the arcuate nucleus. Comparing sexes, we found increased CART mRNA expression in the anteroventral periventricular nucleus of adult females. In other regions including the CA1, the lateral hypothalamic area and the dorsomedial nucleus of the hypothalamus, CART expression was not different comparing postnatal ages and sexes. Our findings indicate that CART gene expression is induced in a distinct temporal and spatial manner in forebrain sites of male and female rats. They also suggest that CART peptide participate in the development of neural pathways related to selective functions including sensory processing, reward and memory formation. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Chronic resistance training decreases MuRF-1 and Atrogin-1 gene expression but does not modify Akt, GSK-3 beta and p70S6K levels in rats

Long-term adaptation to resistance training is probably due to the cumulative molecular effects of each exercise session. Therefore, we studied in female Wistar rats the molecular effects of a chronic resistance training regimen (3 months) leading to skeletal muscle hypertrophy in the plantaris muscle. Our results demonstrated that muscle proteolytic genes MuRF-1 and Atrogin-1 were significantly decreased in the exercised group measured 24 h after the last resistance exercise session (41.64 and 61.19%, respectively; P < 0.05). Nonetheless, when measured at the same time point, 4EBP-1, GSK-3 beta and eIF2B epsilon mRNA levels and Akt, GSK-3 beta and p70S6K protein levels (regulators of translation initiation) were not modified. Such data suggests that if gene transcription constitutes a control point in the protein synthesis pathway this regulation probably occurs in early adaptation periods or during extreme situations leading to skeletal muscle remodeling. However, proteolytic gene expression is modified even after a prolonged resistance training regimen leading to moderate skeletal muscle hypertrophy.

Is gender crucial for cardiovascular adjustments induced by exercise training in female spontaneously hypertensive rats?

Evidence of mild hypertension in women and female rats and our preliminary observation showing that training is not effective to reduce pressure in female as it does in male spontaneously hypertensive rats (SHR) prompt us to investigate the effects of gender on hemodynamic pattern and microcirculatory changes induced by exercise training. Female SHR and normotensive controls (Wistar- Kyoto rats) were submitted to training (55% VO2 peak; 3 months) or kept sedentary and instrumented for pressure and hindlimb flow measurements at rest and during exercise. Heart, kidney, and skeletal muscles (locomotor/ nonlocomotor) were processed for morphometric analysis of arterioles, capillaries, and venules. High pressure in female SHR was accompanied by an increased arteriolar wall: lumen ratio in the kidney (+30%; P < 0.01) but an unchanged ratio in the skeletal muscles and myocardium. Female SHR submitted to training did not exhibit further changes on the arteriolar wall: lumen ratio and pressure, showing additionally increased hindlimb resistance at rest (+29%; P < 0.05). On the other hand, female SHR submitted to training exhibited increased capillary and venular densities in locomotor muscles (+50% and 2.3- fold versus sedentary SHR, respectively) and normalized hindlimb flow during exercise hyperemia. Left ventricle pressure and weight were higher in SHR versus WKY rats, but heart performance (positive dP/dt(max) and negative dP/dt(max)) was not changed by hypertension or training, suggesting a compensated heart function in female SHR. In conclusion, the absence of training- induced structural changes on skeletal muscle and myocardium arterioles differed from changes observed previously in male SHR, suggesting a gender effect. This effect might contribute to the lack of pressure fall in trained female SHRs.

Symptomatic expression of depression among Jewish adolescents: effects of gender and age

Background Depression symptomatology was assessed with the Beck Depression Inventory (BDI) in a sample of Jewish adolescents, in order to compare the frequency and severity of depression with non-Jewish adolescents as well as examine gender difference of the expression of depressive symptomatology. Method Subjects comprised 475 students from Jewish private schools, aged 13-17 years, who were compared with an age-matched non-Jewish sample (n = 899). Kendall`s definition was adopted to classify these adolescents according to level of depressive symptoms. The frequency of depression was calculated for ethnicity, gender and age strata. Discriminant analysis and principal component analysis were performed to assess the importance of depression-specific and non-specific items, along with the factor structure of the BDI, respectively. Results The overall mean score on the BDI in the Jewish and the non-Jewish sample was 9.0 (SD = 6.4) and 8.6 (SD = 7.2), respectively. Jewish girls and boys had comparable mean BDI scores, contrasting with non-Jewish sample, where girls complained more of depressive symptoms than boys (p < 0.001). The frequency of depression, adopting a BDI cutoff of 20, was 5.1% for the Jewish sample and 6.3% for the non-Jewish sample. The frequency of depression for Jewish girls and boys was 5.5% (SE = 1.4) and 4.6% (SE = 1.5), respectively. On the other hand, the frequency of depression for non-Jewish girls and boys was 8.4% (SE = 1.2) and 4.0% (SE = 1.0), respectively. The female/male ratio of frequency of BDI-depression was 1.2 in the Jewish sample, but non-Jewish girls were twice (2.1) as likely to report depression as boys. Discriminant analysis showed that the BDI highly discriminates depressive symptomatology among Jewish adolescents, and measured specific aspects of depression. Factor analysis revealed two meaningful factors for the total sample and each gender (cognitive-affective dimension and somatic dimension), evidencing a difference between Jewish boys and Jewish girls in the symptomatic expression of depression akin to non-Jewish counterparts. Conclusions Ethnic-cultural factor might play a role in the frequency, severity and symptomatic expression of depressive symptoms in Jewish adolescents. The lack of gender effect on depression, which might persist from adolescence to adulthood among Jewish people, should be investigated in prospective studies.

Transcriptome and gene expression profile of ovarian follicle tissue of the triatomine bug Rhodnius prolixus

Insect oocytes grow in close association with the ovarian follicular epithelium (OFE), which escorts the oocyte during oogenesis and is responsible for synthesis and secretion of the eggshell. We describe a transcriptome of OFE of the triatomine bug Rhodnius prolixus, a vector of Chagas disease, to increase our knowledge of the role of FE in egg development. Random clones were sequenced from a cDNA library of different stages of follicle development. The transcriptome showed high commitment to transcription, protein synthesis, and secretion. The most abundant cDNA was a secreted (S) small, proline-rich protein with maximal expression in the vitellogenic follicle, suggesting a role in oocyte maturation. We also found Rp45, a chorion protein already described, and a putative chitin-associated cuticle protein that was an eggshell component candidate. Six transcripts coding for proteins related to the unfolded-protein response (UPR) by were chosen and their expression analyzed. Surprisingly, transcripts related to UPR showed higher expression during early stages of development and downregulation during late stages, when transcripts coding for S proteins participating in chorion formation were highly expressed. Several transcripts with potential roles in oogenesis and embryo development are also discussed. We propose that intense protein synthesis at the FE results in reticulum stress (RS) and that lowering expression of a set of genes related to cell survival should lead to degeneration of follicular cells at oocyte maturation. This paradoxical suppression of UPR suggests that ovarian follicles may represent an interesting model for studying control of RS and cell survival in professional S cell types. (C) 2011 Elsevier Ltd. All rights reserved.

Antimicrobial activity in the tick Rhipicephalus (Boophilus) microplus eggs: Cellular localization and temporal expression of microplusin during oogenesis and embryogenesis

Arthropods display different mechanisms to protect themselves against infections, among which antimicrobial peptides (AMPs) play an important role, acting directly against invader pathogens. We have detected several factors with inhibitory activity against Candida albicans and Micrococcus luteus on the surface and in homogenate of eggs of the tick Rhipicephalus (Boophilus) microplus. One of the anti-M. luteus factors of the egg homogenate was isolated to homogeneity. Analysis by electrospray mass spectrometry (ESI-MS) revealed that it corresponds to microplusin, an AMP previously isolated from the cell-free hemolymph of X (B.) microplus. Reverse transcription (RT) quantitative polymerase chain reactions (qPCR) showed that the levels of microplusin mRNA gradually increase along ovary development, reaching an impressive highest value three days after the adult females have dropped from the calf and start oviposition. Interestingly, the level of microplusin mRNA is very low in recently laid eggs. An enhance of microplusin gene expression in eggs is observed only nine days after the onset of oviposition, achieving the highest level just before the larva hatching, when the level of expression decreases once again. Fluorescence microscopy analysis using an anti-microplusin serum revealed that microplusin is present among yolk granules of oocytes as well as in the connecting tube of ovaries. These results, together to our previous data. suggest that microplusin may be involved not only in protection of adult female hemocele, but also in protection of the female reproductive tract and embryos, what points this AMP as a considerable target for development of new methods to control R. (B.) microplus as well as the vector-borne pathogens. (c) 2009 Elsevier Ltd. All rights reserved.

Differential effects of female sex hormones on cellular recruitment and tracheal reactivity after formaldehyde exposure

Female sex hormones (FSHs) exert profound regulatory effects on the course of lung inflammation due to allergic and non-allergic immune responses. As pollution is one of the pivotal factors to induce lung dysfunction, in this study we investigated the modulatory role of FSHs on lung inflammation after a formaldehyde (FA) exposure. For this purpose, lung and systemic inflammatory responses were evaluated in terms of leukocytes countings in bronchoalveolar lavage (BAL), peripheral blood and bone marrow lavage from 7-day ovariectomized (OVx) and Sham-OVx rats subjected to FA inhalation for 3 consecutive days. The hypothesized link between effects of FSHs on expression of adhesion molecules and mast cells degranulation was also studied. Once exposed to FA, Sham-OVx rats increased the number of total cells recovered in BAL and of leukocytes in peripheral blood, and decreased the counts in bone marrow. By contrast, in OVx rats upon FA exposure there was a reduction of the total cells counts in BAL and of blood leukocytes: lung expressions of ICAM-1 and Mac-1 were depressed, but the number of bone marrow cells did not vary. Estradiol treatment of OVx rats increased the total cells in BAL and decreased the number of blood leukocytes, whereas the number of bone marrow cell remained unaltered. Progesterone treatment, in turn increased the total cells in BAL and blood leukocytes, but decreased the number of bone marrow cells. OVx rats exposed to FA developed tracheal hyperresponsiveness to methacholine (MCh). A similarly altered response was found between the tracheal segments of Sham-OVx rats after FA exposure and that found in tracheae of naive rats. Estradiol treatment prevented FA-induced tracheal hyperresponsiveness to MCh whereas progesterone was ineffective in this regard. In addition, OVx rats upon FA exposure significantly increased both, the ability of mast cell degranulation and serum corticosterone levels. In conclusion, it was found that FSHs act by distinct control mechanisms on FA-induced lung inflammation and tracheal hyperresponsiveness, since at low circulating levels of FSHs (such as those after OVx) there is some resistance to the development of a lung inflammatory response, but the cholinergic tracheal responsiveness is exacerbated. Our data also help to understand the involvement of FSHs on mast cells activity after pollutants exposure and add information regarding the role of FSHs on the mechanisms related to endothelium-leukocyte interactions. (C) 2011 Elsevier Ireland Ltd. All rights reserved.