Multiomics analysis of adaptation to repeated DNA damage in prostate cancer cells.

DNA damage is frequently utilized as the basis for cancer therapies; however, resistance to DNA damage remains one of the biggest challenges for successful treatment outcomes. Critically, the molecular drivers behind resistance are poorly understood. To address this question, we created an isogenic model of prostate cancer exhibiting more aggressive characteristics to better understand the molecular signatures associated with resistance and metastasis. 22Rv1 cells were repeatedly exposed to DNA damage daily for 6 weeks, similar to patient treatment regimes. Using Illumina Methylation EPIC arrays and RNA-seq, we compared DNA methylation and transcriptional profiles between the parental 22Rv1 cell line and the lineage exposed to prolonged DNA damage. Here we show that repeated DNA damage drives the molecular evolution of cancer cells to a more aggressive phenotype and identify molecular candidates behind this process. Total DNA methylation was increased while RNA-seq demonstrated these cells had dysregulated expression of genes involved in metabolism and the unfolded protein response (UPR) with Asparagine synthetase (ASNS) identified as central to this process. Despite the limited overlap between RNA-seq and DNA methylation, oxoglutarate dehydrogenase-like (OGDHL) was identified as altered in both data sets. Utilising a second approach we profiled the proteome in 22Rv1 cells following a single dose of radiotherapy. This analysis also highlighted the UPR in response to DNA damage. Together, these analyses identified dysregulation of metabolism and the UPR and identified ASNS and OGDHL as candidates for resistance to DNA damage. This work provides critical insight into molecular changes which underpin treatment resistance and metastasis.

Expectation violations enhance neuronal encoding of sensory information in mouse primary visual cortex.

The response of cortical neurons to sensory stimuli is shaped both by past events (adaptation) and the expectation of future events (prediction). Here we employed a visual stimulus paradigm with different levels of predictability to characterise how expectation influences orientation selectivity in the primary visual cortex (V1) of male mice. We recorded neuronal activity using two-photon calcium imaging (GCaMP6f) while animals viewed sequences of grating stimuli which either varied randomly in their orientations or rotated predictably with occasional transitions to an unexpected orientation. For single neurons and the population, there was significant enhancement in the gain of orientation-selective responses to unexpected gratings. This gain-enhancement for unexpected stimuli was prominent in both awake and anaesthetised mice. We implemented a computational model to demonstrate how trial-to-trial variability in neuronal responses were best characterised when adaptation and expectation effects were combined.

Selectivity for local orientation information in visual mirror symmetry perception.

Mirror symmetry is a global percept formed from specific arrangements of matching local information. It has been shown that some features of this local information can interact with the global percept, interfering with symmetry perception. One such feature is orientation; it is well established that the orientation of the symmetry axis has a significant impact on symmetry perception, but the role of local orientation of individual elements is still equivocal. Some studies have argued for no role of local orientation in symmetry perception, while other studies have shown a detrimental effect of certain local orientation combinations. Using dynamic stimuli composed of oriented Gabor elements with increasing temporal delay (SOA) between the onset of the first and second element in a symmetric pair, we systematically map how orientation variation within and between symmetric pairs affected the temporal integration of symmetric patterns in five observers. This method allows consideration of both sensitivity to symmetry (threshold, or T0) as well as the duration of visible persistence of each condition through the visual system (P). Our results show a clear role for local orientation in symmetry perception and highlight the importance of local orientation in symmetry perception. Our findings reinforce the need for more nuanced perceptual models incorporating local element orientation, which is currently unaccounted for.

Contribution of higher-order structure to perception of mirror symmetry: Role of shapes and corners.

Visual mirror symmetry is a global feature that is dependent on specific low-level relationships between component elements. Initially conceptualized as virtual lines between paired elements, it has been suggested that higher-order structure between pairs of symmetric elements forming virtual four cornered shapes may also be important for strengthening the percept of mirror symmetry. We utilize corner elements, formed by joining two Gabor elements along a central midline creating vertices with variable internal angles, in a temporal integration paradigm. This allows us to specifically manipulate the presence and type of higher-order versus lower-order structure in patterns with symmetrically placed elements. We show a significant contribution of higher-order structure to the salience of visual symmetries compared with patterns with only lower-order structures. We also find that although we are more sensitive to patterns with higher-order structure, there is no difference in the temporal processing of higher-order versus lower-order patterns. These findings have important implications for existing spatial filter models of symmetry perception that rely on lower-order structures alone and reinforces the need for elaborated models that can more readily capture the complexities of real-world symmetries.

Eliminating brightness induction effects when measuring motion centre-surround suppression of contrast.

The perceived contrast of a central stimulus is supressed when it is embedded in a higher contrast surround, centre-surround suppression of contrast. Local brightness induction effects between the two stimulus regions have been proposed to account for conflicting results when relative grating phases were different. Here, suppression and brightness induction effects are dissociated using a centre-surround arrangement with moving gratings. Four experienced observers were involved in experiments, utilising two-interval forced-choice contrast matching tasks. The stimuli were drifting sinusoidal grating patterns with surrounds (95% contrast) differing in direction of motion and orientation relative to the 40% contrast centre grating. First a 90°-phase-offset same direction surround condition was compared to both same direction (phase aligned) and opposing direction conditions. The reduction in the suppression for the phase-offset condition suggested a reduction in brightness induction influences. Then suppression was examined when surround directions varied and where phase was either fixed or randomised. For small changes in the motion direction between centre and surround (0° to 26.6°) the amount of brightness induction varied sinusoidally with the difference in phase introduced by the direction difference. Finally, the spatial separation between the centre and surround was varied to determine the reduction of suppression and brightness induction with increasing spatial distance. We found both fit an exponential decay function, with surround suppression producing the larger range of influence. Our findings quantify both brightness induction and suppression effects and validate the use of phase randomisation to remove effects of brightness induction when evaluating surround suppression.

Lateral inhibition between banks of orientation selective channels predicts shape context effects: A tilt-illusion field.

The perceived shapes of almost circular paths are modified by concentrically placed context paths. These induced changes have previously been attributed to curvature masking. This paper shows that, instead, they can be explained by the impacts of local tilt illusions. First, the tilt-illusion was measured over the full range of orientation differences between short test and context lines and it was shown that the resulting function can be predicted by a model based on a vectorial population response of a bank of orientation selective channels, provided lateral inhibition between channels with the same orientation selectivity and adjacent receptive fields was postulated. Subsequently, it was demonstrated that, if the perceived shape of a test path were modified to accommodate the predicted local tilt-illusion, then this could account for previously reported changes in the detectability of a path sinusoidally modulated in radius. Further, we measured points of subjective vertical in test lines and points of subjective circularity in test paths when surrounded by modulated context paths. The tilt required to null the tilt-illusion approximated the maximum orientation difference from circular measured in the modulated paths at their point of subjective circularity, supporting the proposal that the illusory shape change is due to local changes in the position of the path arising from a response to local tilt illusions induced by the orientation context. An important corollary to this result is that such effects will generalize to all paths which are adjacent.

Analysis of shape uses local apparent position rather than physical position.

Objects are often identified by the shapes of their boundaries. Here, by measuring threshold amplitudes for detection of sinusoidal modulation of local position, orientation and centrifugal speed in a closed path of Gabor patches, we show that the positions of such boundaries are misperceived to accommodate local illusions of orientation context and motion induced positional bias. These two types of illusion are shown to occur independently, but the misperception of position is additive. We conclude that, in the analysis of shape, the visual system uses the apparent rather than the veridical boundary conformation.

The temporal integration windows for visual mirror symmetry.

Symmetry perception in dot patterns is tolerant to temporal delays of up to 60 ms within and between element pairs. However, it is not known how factors effecting symmetry discrimination in static patterns might affect temporal integration in dynamic patterns. One such feature is luminance polarity. Using dynamic stimuli with increasing temporal delay (SOA) between the onset of the first and second element in a symmetric pair, we investigated how four different luminance-polarity conditions affected the temporal integration of symmetric patterns. All four luminance polarity conditions showed similar upper temporal limits of approximately 60 ms. However psychophysical performance over all delay durations showed significantly higher symmetry thresholds for unmatched-polarity patterns at short delays, but also significantly less sensitivity to increasing temporal delay relative to matched-polarity patterns. These varying temporal windows are consistent with the involvement of a fast, sensitive first-order mechanism for matched-polarity patterns, and a slower, more robust second-order mechanism for unmatched-polarity patterns. Temporal integration windows for unmatched-polarity patterns were not consistent with performance expected from attentional mechanisms alone, and instead supports the involvement of second-order mechanisms that combines information from ON and OFF channels.

Autophagy of mucin granules contributes to resolution of airway mucous metaplasia.

Exacerbations of muco-obstructive airway diseases such as COPD and asthma are associated with epithelial changes termed mucous metaplasia (MM). Many molecular pathways triggering MM have been identified; however, the factors that regulate resolution are less well understood. We hypothesized that the autophagy pathway is required for resolution of MM by eliminating excess non-secreted intracellular mucin granules. We found increased intracellular levels of mucins Muc5ac and Muc5b in mice deficient in autophagy regulatory protein, Atg16L1, and that this difference was not due to defects in the known baseline or stimulated mucin secretion pathways. Instead, we found that, in mucous secretory cells, Lc3/Lamp1 vesicles colocalized with mucin granules particularly adjacent to the nucleus, suggesting that some granules were being eliminated in the autophagy pathway rather than secreted. Using a mouse model of MM resolution, we found increased lysosomal proteolytic activity that peaked in the days after mucin production began to decline. In purified lysosomal fractions, Atg16L1-deficient mice had reduced proteolytic degradation of Lc3 and Sqstm1 and persistent accumulation of mucin granules associated with impaired resolution of mucous metaplasia. In normal and COPD derived human airway epithelial cells (AECs), activation of autophagy by mTOR inhibition led to a reduction of intracellular mucin granules in AECs. Our findings indicate that during peak and resolution phases of MM, autophagy activity rather than secretion is required for elimination of some remaining mucin granules. Manipulation of autophagy activation offers a therapeutic target to speed resolution of MM in airway disease exacerbations.

Motion direction tuning in centre-surround suppression of contrast.

The perceived contrast of a central stimulus is reduced in the presence of a high contrast surround. A number of stimulus features influence the amount of suppression. A two-mechanism model has been proposed for stationary patterns involving a narrowly-tuned process, requiring very similar stimuli in the centre and surround, and a weaker, untuned or very broadly tuned process unselective for stimulus features. This study examines whether a similar model applies to the motion pathway in human participants by varying the orientation and direction of motion of the surround relative to the centre. Four experienced observers completed a two-interval forced-choice contrast matching task. The stimuli were drifting sinusoidal grating patterns with high contrast surrounds (95%) differing in direction of motion and orientation relative to the centre grating. All surround conditions produced suppression but a common orientation and direction of motion produced significantly more suppression than either opposite direction of motion conditions or orthogonal direction conditions. The tuning for motion direction differences was assessed for same and opposite directions of motion. These findings support the extension of the two-mechanism model of contrast suppression to motion direction.

The association between in utero exposure to maternal psychological stress and female reproductive function in adolescence: A prospective cohort study.

Background: Experimental studies suggest that prenatal stress affects reproductive function in female offspring, but human evidence is sparse and inconsistent. In this present study, we aim to investigate whether maternal psychological stress, quantified as stressful life events during pregnancy, affect reproductive function in the female offspring. Method: In a large population-based pregnancy cohort study (The Raine Study) continuously followed from prenatal life through to adolescence we examined the association between the number of maternal stressful life events in both early and late gestation and subsequent ovarian and uterine function in 228 female adolescent offspring. Mothers prospectively reported stressful life events during pregnancy at 18 and 34 weeks using a standardized 10-point questionnaire. Female offspring (n â€‹= â€‹228) age 14-16 years underwent gynecological examination including transabdominal abdominal ultrasound (TAUS) to measure uterine volume and ovarian AFC. Plasma samples on day 2-6 of the spontaneous menstrual cycle measured circulating AMH and inhibin B. Multivariate linear regression analysis was used to examine the associations between maternal stressful life events and reproductive function in female offspring. Adolescents taking hormonal contraception were excluded. Results: Most adolescents (145/228, 64%) were exposed to at least one stressful life event in early gestation and around half (125/228, 55%) were exposed to at least one in later gestation. Exposure to one or more maternal stressful life events in late gestation was associated with a greater uterine volume (ߠ​= â€‹0.13, 95% CI 0.04; 0.23) and higher ovarian AFC (ߠ​= â€‹0.19, 95% CI 0.02; 0.35) at age 14-16 years. No associations between maternal stressful events in late gestation and reproductive function were identified. No associations between stressful life events in early or late gestation and circulating AMH or Inhibin B were observed. Conclusion: Maternal psychological stress in late, but not early gestation was associated with a significantly greater uterine volume and ovarian antral follicle count (AFC) in adolescent offspring but did not affect ovarian production of antimullerian hormone (AMH) or Inhibin B. These findings suggest that female reproductive function is influenced by prenatal exposure to stress.

In utero exposure to maternal stressful life events and risk of polycystic ovary syndrome in the offspring: The Raine Study.

BACKGROUND: PCOS is the most common endocrine disorder in reproductive age women. The origins of PCOS are unknown but experimental and limited human evidence suggests that greater prenatal exposure to androgens may predispose to PCOS. Experimental evidence suggests that maternal stressors may affect reproductive function in the offspring via changes in prenatal androgen exposure. In this present study, we aim to investigate whether maternal stressful life events during pregnancy are associated with polycystic ovary morphology (PCOM) or polycystic ovary syndrome (PCOS) in adolescent offspring. METHOD: In a large population-based pregnancy cohort study (The Raine Study) continuously followed from prenatal life through to adolescence we examined the association between maternal stressful life events during pregnancy in both early and late gestation, and subsequent circulating concentrations of ovarian and adrenal androgens, PCOM and PCOS in the normal menstrual cycle of offspring age 14-16 years. Maternal stressful life events were prospectively recorded during pregnancy at 18 and 34 weeks using a 10-point questionnaire. Female offspring (n = 223) completed a questionnaire about their menstrual cycles, underwent a clinical examination for hirsutism (Ferriman-Gallwey score) and transabdominal pelvic ultrasound examination to determine ovarian morphology according to standardized criteria for classification of PCOM. Plasma samples were obtained at day 2-6 of the normal menstrual cycle for measurement of androgens. PCOM was defined according to the international consensus definition, 2003 and the evidence-based guideline for the assessment and management of PCOS, 2018. PCOS was diagnosed according to Rotterdam criteria and National Institute of Health (NIH) criteria. Multivariate linear and logistic regression analyses were used to examine the associations between maternal stressful life event exposure and ovarian morphology (PCOM), circulating ovarian and adrenal androgens (clinical and biochemical hyperandrogenism (hirsutism)) and presence of PCOS. RESULTS: Of 223 recruited adolescent girls, 78 (35.9%) and 68 (31.3%) had PCOM by the 2003 and 2018 criteria respectively, while 66 (29.6%) and 37 (16.6%) had PCOS, using Rotterdam and NIH criteria, respectively. Most girls (141/223, 63.2%) were exposed to at least one stressful life event in early gestation and around half (121/223, 54.3%) were exposed to at least one stressful life event in late gestation. Maternal stressful life events in early gestation were associated with a statistically significant lower prevalence of PCOM when applying the 2003 criteria [adjusted odds ratio [aOR] and 95% confidence intervals (CI): 0.74 (95% CI: 0.55; 0.99)], and a similar association was detected when applying the 2018 PCOM criteria (aOR, 0.69, 95% CI: 0.50; 0.95)]. Maternal stressful life events in early gestation were also associated with lower circulating concentrations of testosterone (ß = -0.05, 95% CI: -0.09; -0.004) and androstenedione (ß = -0.05, 95% CI: -0.10; -0.002) in the offspring. No similar effects for PCOM or circulating androgens were detected in late gestation. No statistically significant associations between maternal stressful life events in early or late gestation with PCOS (neither Rotterdam nor NIH criteria) in adolescence were detected. The prospective collection of maternal stressful life events during both early and late gestation and direct measurement of PCOM, PCOS and circulating androgens in adolescence and key co-variates implies minimal possibility of recall, information bias and selection bias. CONCLUSION: Maternal exposure to stressful life events in early gestation is associated with significantly reduced circulating ovarian and adrenal androgen concentrations in adolescence (testosterone and androstenedione), and an indication of fewer cases of polycystic ovary morphology (PCOM) defined by the 2003 international consensus definition and by the 2018 international evidence-based guideline, but has no effect on polycystic ovary syndrome (PCOS), diagnosed using either Rotterdam or NIH criteria.

Neonatal outcomes following previable prelabour rupture of membranes before 23 weeks of gestation - A retrospective cohort study.

OBJECTIVE: To compare outcomes of hospitalized preterm infants following previable prelabour rupture of membranes (PPROM) at≤23 weeks of gestation. METHODS: Retrospective cohort study of preterm infants admitted for intensive care, between January 2006 and December 2016 following PPROM, was conducted. Short term clinical outcomes included severity of respiratory morbidity, length of hospital stay and mortality. Neurodevelopment in survivors was assessed using Bayley's Scales of Infant Development (3rd edition) at 24 months corrected age. RESULTS: A total of 82 preterm infants were admitted following PPROM at < 23 weeks and were grouped as: Group 1 (n = 28) with PPROM < 20 weeks and Group 2 (n = 54) with PPROM between 20-22 + 6 weeks. Median latency following PPROM was significantly longer in Group 1 infants [69(Interquartile range (IQR): 43-74; Range (R): 25-100 vs. 29(IQR: 10-53; R: 2-72) days, p < 0.001]. Median gestation at delivery was 27.4 weeks (Group 1) vs. 25.1 weeks (Group 2). Group 1 had a significantly higher incidence of oligohydramnios [13(46.4%) vs. 8(14.8%), p = 0.002], lower Apgar scores (<7) at 5 minutes [19(67.9%) vs. 24(44.4%), p = 0.044], increased pulmonary hypoplasia [13(46.4%) vs. 5(9.3%), p < 0.001], joint contractures [3(10.7%) vs. 0, p = 0.037] and mortality [10(35.7%) vs. 7(13.0%), p = 0.016]. Neurodevelopmental outcomes at 24 months corrected age were comparable in the 36 surviving infants (9/18 vs. 27/547). CONCLUSION: Morbidity and mortality is high in infants born after previable PPROM; specifically, in those with PPROM < 20 weeks although early childhood neurodevelopmental outcomes were comparable. Larger prospective studies focussing on long term neonatal outcomes are needed to confirm these findings.

Shape partitioning interacts with global shape integration.

Objects are often identified by the shape of their profiles but complex objects are often comprised of multiple articulated components. It has been proposed that complex objects are decomposed and recognized by their component parts. This study exploits the proposition that the visual system decomposes objects at matched deep concavities on their boundaries. Rapid decreases in thresholds for detection of sinusoidal deformation of a circle's radius with number of cycles of modulation shows that shape information is integrated around radial frequency (RF) patterns. Here we merge RF patterns to form composite patterns with concavities and show that integration around the RF patterns is disrupted if the concavities are shallow but preserved if they are deep, consistent with their decomposition at matched deep concavities. Geon theory identifies complex patterns through a structural description of viewpoint invariant primitives known as geons. Geons are defined by properties on their boundaries that co-occur in a non-accidental manner across viewpoint changes rather than by reconciling metric properties such as curvature with viewpoint specific templates. Similarly, shapes of RF patterns are defined by the positions of curvature features on their boundaries. We argue that RF patterns provide flexible stimuli that might be used to study geons.

A new visual illusion of aspect-ratio context.

Perception of local properties of the visual field is influenced by aftereffects of adaptation. The tilt aftereffect describes repulsion of the perceived orientation of a line from the orientation of an adapting line. Analogous effects of spatial context are often called illusions. Repulsion of the perceived orientation of a grating from the orientation of a surrounding grating is referred to as the tilt illusion. In the same manner, the size aftereffect and Ebbinghaus illusion form a complementary pair of temporal and spatial context effects of size. Here we report psychophysical evidence for a previously unknown aspect-ratio illusion which causes the perceived aspect-ratio of a rectangle to be repelled from the aspect-ratio of rectangles surrounding it. This illusion provides a spatial analogue to the aspect-ratio aftereffect.

The association between in-utero exposure to stressful life events during pregnancy and male reproductive function in a cohort of 20-year-old offspring: The Raine Study.

STUDY QUESTION: Is exposure to gestational stress in the critical time window for the normal differentiation and growth of male reproductive tissue associated with male reproductive function in offspring in later life? SUMMARY ANSWER: Exposure to stressful life events (SLEs) in early, but not late gestation, are associated with reduced adult male reproductive function, consistent with the hypothesis that events during early prenatal life programme adult male reproductive function. WHAT IS ALREADY KNOWN: Animal studies suggest that gestational stress may impact on the reproductive function of male offspring, but human evidence is sparse. STUDY DESIGN, SIZE, DURATION: Using a prospective longitudinal cohort, we examined the association between number and type of maternal stressors during pregnancy in both early and late gestation and reproductive function in 643 male Generation 2 (offspring) at age 20 years. Mothers and their male Generation 2 (offspring) from The Raine Study participated. Mothers prospectively reported SLEs during pregnancy recorded at gestational weeks 18 and 34 using a standardized 10-point questionnaire. PARTICIPANTS/MATERIALS, SETTING, METHODS: The 643 male Generation 2 (offspring) underwent testicular ultrasound examination and semen analysis and provided serum for reproductive hormone analysis. Multivariate linear regression analysis was used to examine associations. MAIN RESULTS AND ROLE OF CHANCE: Of 643 recruited males, 407 (63%) were exposed to at least one SLE in early gestation. Fewer SLEs were reported in late gestation (n = 343, 53%). Maternal SLE exposure in early gestation was negatively associated with total sperm count (ß = -0.31, 95% CI -0.58; -0.03), number of progressive motile sperm (ß = -0.15, 95% CI -0.31; 0.00) and morning serum testosterone concentration (ß = -0.04, 95% CI -0.09; -0.00). No similar effects of maternal SLE exposure in late pregnancy were detected. The large sample size and an objective detailed direct assessment of adult male reproductive function with strict external quality control for sperm quality, as well as detailed prospectively collected information on prenatal SLEs in two distinct time windows of pregnancy reported by the women in early and late gestation along with other risk factors, imply minimal possibility of recall, information bias and selection bias. When assessing our results, we adjusted for a priori chosen confounders, but residual confounding or confounding by factors unbeknown to us cannot be ruled out. LIMITATIONS, REASONS FOR CAUTION: It is not possible to measure how SLEs impacted differently on the mother's experience or perception of stress. Resilience (coping) gradients may alter cortisol levels and thus modify the associations we observed and the mothers' own perception of stress severity may have provided a more precise estimate of her exposure. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that exposure to SLEs in early, but not late gestation, are associated with reduced adult male reproductive function. Improved support for women with exposure to SLEs during pregnancy, particularly during the first trimester, may improve the reproductive health of their male offspring in later life. Intervention studies of improved pregnancy support could provide more insight into this association and more information is needed about the potential specific epigenetic mechanisms underlying this association. STUDY FUNDING/COMPETING INTEREST(S): The male fertility sub-study was funded by NHMRC Grant 634 457. The core management of the Raine Study is funded by University of Western Australia, Curtin University, Telethon Kids Institute, Women and Infants Research Foundation, Edith Cowan University, Murdoch University, The University of Notre Dame Australia and Raine Medical Research foundation. Dr Bräuner's salary was supported by Læge Sofus Carl Emil Friis og Hustru Olga Doris Friis foundation in Denmark. All authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Phase specific shape aftereffects explained by the tilt aftereffect.

Aftereffects of adaptation are frequently used to infer mechanisms of human visual perception. Commonly, the properties of stimuli are repelled from properties of the adaptor. For example, in the tilt aftereffect a line is repelled in orientation from a previously experienced line. Perceived orientation is predicted by the centroid of the responses of a population of mechanisms individually tuned to limited ranges of orientation but collectively sensitive to the whole possible range. Aftereffects are also predictable if the mechanisms are allowed to adapt. Adaptation across radial frequency patterns, patterns deformed from circular by a sinusoidal modulation of radius, causes repulsive aftereffects, sensitive to the relative amplitudes and orientations of the patterns. Here we show that these shape aftereffects can be accounted for by the application of local tilt aftereffects around the shape contour. We suggest that fields of tilt aftereffects might provide a general mechanism for exaggerating the perceptual difference between successively experienced stimuli, making them more discriminable. If the human visual system does indeed exploit this possibility, then the conclusions often made by studies assuming adaptation within mechanisms sensitive to the shape of stimuli will need to be reconsidered. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Associations between major dietary patterns and testicular function in a population-based cohort of young men: results from the Western Australian Pregnancy Cohort (Raine) Study.

BACKGROUND: Controversial speculation suggestions that dietary intake may affect semen quality and testicular function, however, there are limited comprehensive studies observing dietary patterns. OBJECTIVE: To study associations between major dietary patterns and markers of testicular function in adulthood. MATERIAL AND METHODS: Observational cross-sectional study of two hundred and ninety men with an average age of 20 years, from the Western Australian Pregnancy Cohort (Raine) Study. Usual dietary intake assessed using a semi-quantitative food frequency questionnaire at 20 years of age. Two dietary patterns previously identified using exploratory factor analysis ("Healthy" or "Western") and participants received z-scores for each dietary pattern. Primary endpoints were testicular volume, total sperm per ejaculate, morning serum testosterone concentration. Secondary endpoints were semen sample parameters, inhibin B and sex steroids (DHT: 3α-diol, 3ß-diol; LH; FSH; DHEA; estradiol; estrone). RESULT(S): Participants were on average 20.0 ± 0.4 years old, had a median of 2 days sexual abstinence and a body mass index of 24.1 ± 3.9 kg/m2 , 13% were smokers, 52% were 'moderate' alcohol drinkers, 23% frequently used recreational drugs and 68% reported 'high' physical activity levels. Sperm concentration and DHT 3α-diol were negatively associated with a greater z-score for the "Western" dietary pattern (p = 0.007 and; p = 0.044, respectively), and serum estradiol concentration was positively associated with a "Western" dietary pattern (p = 0.007) after adjustment for BMI, varicocele, cryptorchidism and sexual abstinence. DISCUSSION: Despite associations between greater intake of the "Western" dietary pattern and a decreased male reproductive health markers, our lack of consistent associations of either a "Healthy" or a "Western" dietary pattern, limit clinical or biological significance in isolation. CONCLUSIONS: A potential negative association of a "Western" dietary pattern with male reproductive health was detected and should be studied further in population-based studies.