Do contrasting socio-ecological conditions bring difference in premenstrual syndrome and its concomitants? A sedente-migrant comparative study from Eastern India.

OBJECTIVES: We asked in our research whether the premenstrual syndrome (PMS) and its concomitants, differ between "sedente" and "migrant" populations hailing from the same ethnic group, owing to their living in contrasting socio-ecological conditions. METHODS: A total of 501 Oraon adolescents (sedente: 200, migrant: 301) were studied. Data on PMS was reported retrospectively using a list of 29 standard symptoms. Principal component analysis (PCA) was applied on PMS. PCA, which resulted in six principal components (PC1 to PC6) were loaded with "behavioral and cognitive," "negative mood," "pain and fluid retention," "vestibular and breast tenderness," and "fatigue," and/or "gastrointestinal" symptoms. Step-wise hierarchical regression was applied using migration status (step 1), socio-demographic (step 2), menstrual (step 3), and nutritional and lifestyle variables (step 4) as concomitants for each principal component. RESULTS: Significantly, a greater number of migrants reported PMS but of milder intensity, unlike the sedentes. Significant sedente-migrant differences were found in the concomitants for PMS. Multivariate analyses showed differential socio-demographic (occupational, educational and wealth status, religion), nutritional (dietary carbohydrate protein and fat, tea intake, body mass index, percent body fat, waist hip ratio, fat mass index), menstrual (age at menarche, cycle length, dysmenorrhoea) and anemic status of the sedentes and the migrants were significantly associated with PMS. CONCLUSIONS: Sedente and migrant participants, despite hailing from the same ethnic group, sharply differed in the prevalence of PMS and its concomitants owing to their living in contrasting socio-ecological conditions.

Do maternal obstetric morbidity and its concomitants differ between sedente and migrant groups? The case of the Oraon populations of Eastern India.

The state of pregnancy and child birth is a stretch of intense vulnerability and incurs reproductive cost, which is governed within a specific socio-ecological context. We asked in our research whether the obstetric morbidities at three stages: antepartum, intrapartum and postpartum, and their concomitants differed significantly between sedente and migrant populations. 403 Oraon indigenous women [203 sedente and 200 migrants] living in Eastern India were selected. Data on socio-demographic, reproductive, maternal health care services and obstetric morbidities were collected using semi structured schedules. We applied Categorical Principal Component Analysis (CATPCA) on the first three variables; PC1 and PC4 were loaded with "socio-demographic and maternal health care services" and PC2 and PC3 loaded with "socio-demographic and reproductive" variables. We applied Poisson regression to examine the determinants of obstetric morbidities. Bivariate analyses showed significant (p ≤ 0.05) sedente-migrant differences in variables related to socio-demographic, reproductive, maternal health care and obstetric morbidities. Poisson regression showed migrants were more likely (p ≤ 0.001) to experience ante and intrapartum morbidities than the sedentes, after controlling the confounders. PC1, PC2 and PC3 could significantly (p ≤ 0.05) predict ante and intrapartum morbidities. For postpartum morbidities, barring the variables related to availing of maternal health care services at the time of child delivery and post delivery, neither migration status nor any of the PCs was a significant predictor. For example, participants who delivered their child in health institutions and had episiotomy and/or caesarean delivery (p ≤ 0.01); and those who availed first PNC within the 24 hours of delivery, stayed under medical supervision after delivery for more than 48 hours and received higher coverage of PNCs were more and less likely respectively (p ≤ 0.05) to have experienced postpartum morbidities. We conclude that the maternal obstetric morbidities and their concomitants differed between sedente and migrant Oraon populations owing to their living in differential socio-ecological contexts.

Pathways that determine the fertility of sedente and migrant Oraon populations of Eastern India: a structural equation modelling approach.

Within local socio-ecological context, the fertility determinants of a population are mediated through complex interrelated physiological and behavioural pathways. We aimed to find out the direct and indirect determinants of fertility of sedente and migrant Oraon populations using Structural Equation Model (SEM). Bivariate analysis showed significant (p ≤ 0.05) sedente-migrant differences in socio-demographic, reproductive, contraceptive, and reproductive and sexual decision-making variables. Results of SEM showed migration status, age at first conception, contraceptive preference and reproductive and sexual decision making have direct but negative association (p ≤ 0.05), and age of the participants, under-five mortality and preference for male child have direct but positive association with fertility (p ≤ 0.05). These variables are also associated with fertility through certain mediated pathways (p ≤ 0.05) like ages at first conception with contraceptive preferences, reproductive and sexual decision-making ability (positive), under-five mortality and desired family size (negative). Educational status of the spouses showed indirect association (p ≤ 0.05) with fertility through four pathways: (i) contraceptive preferences; (ii) reproductive and sexual decision-making ability; (iii) ages at first conception (positive); and (iv) desired family size (negative). Hence, sedente and migrant participants reflected a sharp difference in the determinants of fertility owing to differential local socio-ecological attributes.

Do vasomotor and genitourinary symptoms of menopause vary between sedente and migrant groups? A study on the Oraon tribal populations of Eastern India.

OBJECTIVES: Human reproductive characteristics are embedded within local ecological contexts. A shift in the local ecology is likely to offer challenges in reproductive outcome. We aimed to investigate sedente-migrant variation in experiencing vasomotor and genitourinary symptoms at perimenopausal and postmenopausal stages and its concomitants. METHODS: Four hundred Oraon tribal populations living in Eastern India (sedente [100 each from perimenopausal and postmenopausal groups] and migrants [100 each from perimenopausal and postmenopausal groups]) were studied. Data on vasomotor and genitourinary symptoms, socio-demographic and reproductive history, body compositions, lifestyle variables, and energy intake were compared between sedente and migrant independently for perimenopausal and postmenopausal groups. Principal component analysis (PCA) was used to identify the principal components (PCs) of menopausal symptoms. A two level multilevel linear regression was applied independently for perimenopausal and postmenopausal groups to identify the concomitants of menopausal symptoms and estimate sedente-migrant variance. RESULTS: Bivariate analysis showed significant (p ≤ .05) sedente-migrant differences in socio-demographic, reproductive, body composition, energy intake, and lifestyle variables and in some of the vasomotor and genitourinary symptoms. In multilevel analyses, random effect did not show significant heterogeneity between sedente and migrant groups in experiencing menopausal symptoms; however, fixed effect showed that region from which participants were recruited (Gram Panchayat [GP]) and individual level characteristics were concomitants (p ≤ .05) for menopausal symptoms, irrespective of menopausal status. CONCLUSION: Variability at GP levels and individual level characteristics of sedente and migrant groups predominantly determined menopausal symptoms of the study populations, but not the migration status.

N-acetyl-L-cysteine increases MnSOD activity and enhances the recruitment of quiescent human fibroblasts to the proliferation cycle during wound healing.

The rebuilding of the connective tissue during wound healing requires the recruitment of fibroblasts to the wound area as well as reentry of quiescent fibroblasts to the proliferative cycle. Whether this process can be modulated by a small molecular weight thiol antioxidant N-acetyl-L-cysteine (NAC) was tested in normal human skin fibroblasts (NHFs) using a uni-directional wound healing assay. NAC treated cells demonstrated a decreased migration rate but increased number of proliferating cells recruited into the wound area post wounding. Fifteen day quiescent control and NAC treated NHFs were re-plated at a lower density and cell numbers counted at different days post-plating. Interestingly, NAC treated cells exhibited increased cellular proliferation indicated by both decreased cell population doubling time and increased S phase cells. NAC treated cells demonstrated decreased steady state levels of reactive oxygen species as well as increased protein and activity levels of manganese superoxide dismutase (MnSOD). NAC treatment failed to induce proliferation in quiescent cells lacking MnSOD expression. These results demonstrate that NAC enhanced the recruitment of quiescent NHFs into proliferation cycle during wound healing. Our results also suggest that the wound healing properties of NAC might be due to its ability to induce and enhance MnSOD expression and activity. Altogether, these findings suggest NAC might be potentially developed as a dietary intervention to improve tissue injury in animals and humans.

Hydroxytyrosol inhibits chemokine C-C motif ligand 5 mediated aged quiescent fibroblast-induced stimulation of breast cancer cell proliferation.

Cancer is an age-associated disease. Although the mechanisms of age-associated increase in cancer incidence are not completely understood, it is believed that the tumor stromal environment significantly influences epithelial malignancy. Fibroblasts are a major cell type in the stroma and, under normal conditions, fibroblasts reside in the quiescent state. Cellular quiescence is a reversible process where cells enter into the proliferative cycle and then exit back to quiescence. We have shown previously that quiescent fibroblasts lose their proliferative capacity as they age, and we defined this mode of cellular aging as chronological life span. Using conditioned media and co-culture experiments, results from this study show that normal human fibroblasts (NHFs) nearing the end of their chronological life span stimulate the proliferation of MB231 and MCF7 human breast epithelial cancer cells. Chemokine C-C motif ligand 5 (CCL5) expression was found to be approximately 8-fold higher in old compared to that in young quiescent NHFs, which correlated with an increase in the ERK1/2-cyclin D1 pro-proliferative pathway in MB231 cells. Conditioned media treated with anti-CCL5 antibody suppressed the activation of the ERK1/2-cyclin D1 pathway and proliferation of MB231 cells. Hydroxytyrosol, a dietary polyphenol and an active ingredient of olive, inhibited CCL5 expression in aging quiescent NHFs. This inhibition was associated with NHFs inability to activate the ERK1/2-cyclin D1 pathway and enhance proliferation of MB231 cells. These results show that fibroblasts nearing the end of their chronological life span promote proliferation of human breast epithelial cancer cells and dietary polyphenols inhibit this process.

MnSOD activity regulates hydroxytyrosol-induced extension of chronological lifespan.

Chronological lifespan (CLS) is defined as the duration of quiescence in which normal cells retain the capacity to reenter the proliferative cycle. This study investigates whether hydroxytyrosol (HT), a naturally occurring polyphenol found in olives, extends CLS in normal human fibroblasts (NHFs). Quiescent NHFs cultured for a long duration (30-60 days) lose their capacity to repopulate. Approximately 60% of these cells exit the cell cycle permanently; a significant increase in the doubling time of the cell population was observed. CLS was extended in quiescent NHFs that were cultured in the presence of HT for 30-60 days. HT-induced extension of CLS was associated with an approximately 3-fold increase in manganese superoxide dismutase (MnSOD) activity while there was no change in copper-zinc superoxide dismutase, catalase, or glutathione peroxidase protein levels. Quiescent NHFs overexpressing a dominant-negative mutant form of MnSOD failed to extend CLS. HT suppressed age-associated increase in mitochondrial ROS levels. Results from spectroscopy assays indicate that HT in the presence of peroxidases can undergo catechol-semiquinone-quinone redox cycling generating superoxide, which in a cellular context can activate the antioxidant system, e.g., MnSOD expression. These results demonstrate that HT extends CLS by increasing MnSOD activity and decreasing age-associated mitochondrial reactive oxygen species accumulation.

MnSOD activity protects mitochondrial morphology of quiescent fibroblasts from age associated abnormalities.

Previously, we have shown manganese superoxide dismutase (MnSOD) activity protects quiescent human normal skin fibroblasts (NHFs) from age associated loss in proliferative capacity. The loss in proliferative capacity of aged vs. young quiescent cells is often characterized as the chronological life span, which is clearly distinct from replicative senescence. We investigate the hypothesis that MnSOD activity protects the mitochondrial morphology from age associated damage and preserves the chronological life span of quiescent fibroblasts. Aged quiescent NHFs exhibited abnormalities in mitochondrial morphology including abnormal cristae formation and increased number of vacuoles. These results correlate with the levels of cellular reactive oxygen species (ROS) and mitochondrial morphology in MnSOD homozygous and heterozygous knockout mouse embryonic fibroblasts. The abnormalities in mitochondrial morphology in aged quiescent NHFs cultured in presence of 21% oxygen concentration were more severe than NHFs cultured in 4% oxygen environment. The alteration in mitochondrial morphology was associated with a significant increase in cell population doubling: 54h in 21% compared to 44h in 4% oxygen environment. Overexpression of MnSOD decreased ROS levels, and preserved mitochondrial morphology in aged quiescent NHFs. These results demonstrate that MnSOD activity protects mitochondrial morphology and preserves the proliferative capacities of quiescent NHFs from age associated loss.