Browsing by Author "Sriparna Pal"

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BPS-induced ovarian dysfunction: Protective actions of melatonin via modulation of SIRT-1/Nrf2/NFĸB and IR/PI3K/pAkt/GLUT-4 expressions in adult golden hamster
(John Wiley and Sons Inc, 2023) Sriparna Pal; Aishwarya Sahu; Rakesh Verma; Chandana Haldar
Ever-increasing occurrence of plastic-manufacturing industries leads to environmental pollution that has been associated with declined human health and increased incidence of compromised reproductive health. Female subfertility/infertility is a complex phenomenon and environmental toxicants as well as lifestyle factors have a crucial role to play. Bisphenol S (BPS) was believed to be a “safer” replacement of bisphenol A (BPA) but recent data documented its neurotoxic, hepatotoxic, nephrotoxic, and reprotoxic attributes. Hence based on the scarcity of reports, we investigated molecular insights into BPS-induced ovarian dysfunction and protective actions of melatonin against it in adult golden hamsters, Mesocricetus auratus. Hamsters were administered with melatonin (3 mg/kg BW i.p. alternate days) and BPS (150 mg/kg BW orally every day) for 28 days. BPS treatment disrupted hypothalamo–pituitary–ovarian (HPO) axis as evident by reduced gonadotropins such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH), ovarian steroids such as estradiol (E2) and progesterone (P4), thyroid hormones namely triiodothyronine (T3) and thyroxine (T4) and melatonin levels along with their respective receptors (ERα, TRα, and MT-1) thereby reducing ovarian folliculogenesis. BPS exposure also led to ovarian oxidative stress/inflammation by increasing reactive oxygen species and metabolic disturbances. However, melatonin supplementation to BPS restored ovarian folliculogenesis/steroidogenesis as indicated by increased number of growing follicles/corpora lutea and E2/P4 levels. Further, melatonin also stimulated key redox/survival markers such as silent information regulator of transcript-1 (SIRT-1), forkhead box O-1 (FOXO-1), nuclear factor E2-related factor-2 (Nrf2), and phosphoinositide 3-kinase/protein kinase B (PI3K/pAkt) expressions along with enhanced ovarian antioxidant capacity. Moreover, melatonin treatment reduced inflammatory load including ovarian nuclear factor kappa-B (NFĸB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) expressions, serum tumor necrosis factor α (TNFα), C-reactive protein (CRP) and nitrite–nitrate levels as well as upregulated ovarian insulin receptor (IR), glucose uptake transporter-4 (GLUT-4), connexin-43, and proliferating cell nuclear antigen (PCNA) expressions in ovary thereby ameliorating inflammatory and metabolic alterations due to BPS. In conclusion, we found severe deleterious impact of BPS on ovary while melatonin treatment protected ovarian physiology from these detrimental changes suggesting it to be a potential preemptive candidate against environmental toxicant-compromised female reproductive health. © 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Environmental toxicant compromised reproductive health: Rescue by melatonin
(Nova Science Publishers, Inc., 2020) Jitendra Kumar; Sriparna Pal; Shruti R. Hansda; Chandana Haldar; Rakesh Verma
Several factors are responsible for declined male and female reproductive potential such as altered lifestyle, nutritional deficiency, global industrialization and increased exposure to environmental toxicants. The World Health Organization documents that around 15% couples face the problems of infertility but its underlying aetiology and treatment still need to be explored. Increased exposure to environmental toxins impair testicular and ovarian physiology through modulation of metabolic status (IR-GLUTs), redox (SIRT-1/Nrf-2/HO-1), inflammatory (NF-κB/COX-2) and apoptotic (Bax/Bcl-2 ratio, caspase-3) proteins and thus compromises reproductive health. Moreover, environmental contaminants have been reported in human blood, urine and milk. Melatonin, a pineal hormone, controls numerous physiological functions and act as an antioxidant, antiapoptotic, anti-inflammatory molecule in various organisms including human. Extra pineal organs such as retina, cerebellum, gastrointestinal tract and reproductive organs are also the source of melatonin. Within gonads, presence of Aralkylamine N-acetyltransferase (AANAT) and N-acetylserotonin O-methyltransferase (ASMT) convinced the intra gonadal synthesis of melatonin. Further, melatonin receptor (MT-1/2) has been reported in testicular Leydig cells, Sertoli cells, sperm and ovarian granulosa cells of mammals including humans that altogether reinforced its autocrine and paracrine role in regulation of reproductive physiology. Recently, melatonin has been reported to modulate various transcription factors and proteins that controls metabolic status and survival factors such as SIRT-1/Nrf-2 and its downstream signalling pathway in various organs including gonads. Therefore, advancement in melatonin research suggests that it could be use for the treatment of fertility related problems and improve the reproductive health. © 2021 Nova Science Publishers, Inc.
Impact of photoperiod on uterine redox/inflammatory and metabolic status of golden hamster, Mesocricetus auratus
(John Wiley and Sons Inc, 2022) Sriparna Pal; Chandana Haldar; Rakesh Verma
Photoperiod modulates reproductive physiology at multiple levels in seasonally breeding animals. Golden hamsters are long-day breeders that diminish their fertility during the short days. Photoperiod is known to regulate hormonal milieu and uterus is a hormone-sensitive dynamic tissue. However, there is lack of molecular insight regarding the impact of photoperiod on uterine physiology with respect to redox and metabolic status in Mesocricetus auratus. We evaluated the impact of photoperiod on circulatory hormonal parameters (triiodothyronine [T3], thyroxin [T4], estradiol [E2], progesterone [P4], melatonin, and insulin), their receptor expressions and key markers associated with redox (SIRT-1/FOXO-1), inflammatory (NFĸB/COX-2) and metabolic (IR/GLUT4) status in uterus. Adult female golden hamsters were exposed to different photoperiodic regimes, that is, short photoperiod (SP; 8L:16D) and long photoperiod (LP; 16L:8D) for 12 weeks. SP drastically decreased peripheral hormone profiles (T3, T4, E2, and P4) and compromised uterine histoarchitecture when compared with LP-exposed hamsters. Further, SP markedly decreased thyroid hormone receptor-α (TRα), insulin receptor, and glucose uptake transporter-4 (GLUT-4) expressions in uterus. We noted enhanced uterine oxidative (increased MDA and decreased SOD/CAT levels), SIRT-1/FOXO-1 expression and inflammatory (NFĸB/COX-2) load in SP condition. Further, elevated levels of circulatory insulin, melatonin, and its receptor (MT-1) expression in uterus was noted under SP condition. Thus, we may suggest that photoperiod might regulate uterine seasonality through modulation of local hormonal and redox/metabolic homeostasis thereby may restrict offspring bearing capacity under short days. © 2022 Wiley Periodicals LLC.
Melatonin attenuates LPS-induced ovarian toxicity via modulation of SIRT-1, PI3K/pAkt, pErk1/2 and NFĸB/COX-2 expressions
(Academic Press Inc., 2022) Sriparna Pal; Chandana Haldar; Rakesh Verma
The association between inflammation and metabolic disturbances leads to various female pathophysiological conditions. Bacterial lipopolysaccharide (LPS), found in the outer membrane of gram-negative bacteria, elicits an oxidative and inflammatory response that profoundly interferes with female reproductive health. We investigated the ameliorative action of melatonin on LPS-induced ovarian pathophysiology in golden hamsters, Mesocricetus auratus. Hamsters were administered with exogenous melatonin (5 mg/kg BW) and LPS (100 μg/kg BW) intraperitoneally for 7 days. LPS treatment impaired ovarian folliculogenesis as evident by histoarchitecture (elevated number of atretic follicles, reduced number of growing follicles and corpus luteum) and steroidogenesis (decreased aromatase/ERα, estradiol and progesterone). On the other hand, LPS administration also perturbed thyroid hormone (T3 and T4) homeostasis, ovarian melatonin receptor (MT-1) expression, antioxidant potential (SOD and catalase) and concomitantly elevated nitro-oxidative stress (decreased SOD, catalase and elevated CRP, TNFα and nitrate/nitrite level) and inflammatory load (NFĸB and COX-2) which culminated into ovarian follicular apoptosis (elevated caspase-3). LPS also disrupted metabolic homeostasis as indicated by hyperinsulinemia with a simultaneous decrease in ovarian IR/GLUT-4 and glucose content. Moreover, LPS treatment decreased expressions of key markers of ovarian physiology (SIRT-1, pErk1/2, PI3K and pAkt). Melatonin co-treatment with LPS improve these detrimental changes proposing melatonin as a potent therapeutic candidate against ovarian dysfunction induced by endotoxin. © 2022 Elsevier Inc.
Photoperiod modulates oestrogen status, insulin interposed glucose uptake and connexin-43 in testes of golden hamster, Mesocricetus auratus
(Taylor and Francis Ltd., 2020) Sriparna Pal; Rakesh Verma; Jitendra Kumar; Chandana Haldar
The environmental photoperiod plays an important role in regulation of seasonal reproductive events. However, with reference tooestrogen status the exact mechanism involved in testicular seasonality is still unclear in general and especially in long-day breeder golden hamster, Mesocricetus auratus. Therefore, in the present study we explored the effect of day length (long day, LD and short day, SD) in modulation of oestrogen level, metabolic and gap junction markers expressionin testes. Our results suggest that LD exposureinduced normal testicular activity as evident by histoarchitectural analyses showing different stages of spermatogenesis, spermatozoa filled lumen and normal Leydig cells. Furthermore, LD upregulated testicular metabolic parameters such as IR, GLUT-8, glucose leveland LDH activity along with predominant testicular gap junction protein (Connexin-43) expression as compared to SD. On the other hand, the expressions of ER-α, aromatase and caspase-3 were reduced under LD condition as compared to SD. Thus, it can be inferred that photoperiod modulates the circulatoryoestrogen level, along with gap junction protein and apoptosis markers expression in testes and harmonizes the energy homeostasis involved in reproductive maintenance for seasonality of golden hamster. Therefore, we may conclude that day-length-mediatedoestrogen is a prominent modulator of male reproductive health. Abbreviations: Insulin receptor (IR); Glucose uptake transporter-8 (GLUT-8); Estrogen receptor-alpha (ER-α); Connexin-43 (Cxn-43); Lactate dehydrogenase (LDH). © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.
Photoperiodic modulation of ovarian metabolic, survival, proliferation and gap junction markers in adult golden hamster, Mesocricetus auratus
(Elsevier Inc., 2022) Sriparna Pal; Chandana Haldar; Rakesh Verma
Female reproductive physiology is greatly dependent on tight regulation of metabolic and survival factors. Photoperiod regulates female reproductive rhythms but very less information exists explaining whether photoperiod could modulate thyroid hormone homeostasis, metabolic/energy parameters along with survival, proliferation and gap junction proteins in the ovary of a long-day breeder, Mesocricetus auratus. Adult female hamsters were exposed to different photoperiodic regimes i.e., critical photoperiod (CP; 12.5L:11.5D), short photoperiod (SP; 8L:16D) and long photoperiod (LP; 16L:8D) for 12 weeks. LP upregulated thyroidal and gonadal activity as apparent by histoarchitecture, thyroid hormone profile [triiodothyronine (T3), thyroxin (T4) and thyroid stimulating hormone (TSH)], luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2) and progesterone (P4) levels when compared with SP exposed hamsters. Further, LP increased thyroid hormone receptor-α/deiodinase-2 (TRα/Dio-2), estrogen receptor-α (ERα)/aromatase and insulin receptor/glucose transporter-4 (IR/GLUT-4) expressions in ovary. Interestingly, ovarian sirtuin-1 (SIRT-1) expression was also upregulated under LP condition along with cell proliferation (proliferating cell nuclear antigen or PCNA), survival (B cell lymphoma-2 or Bcl-2) and gap junction (connexin-43) markers when compared to SP exposed hamsters. We also noted elevated levels of circulatory leptin, insulin along with melatonin and its receptor (MT-1) in ovary under SP condition. Thus, we suggest that photoperiod plays a vital role in regulation of thyroid and reproductive hormone homeostasis along with key metabolic and survival markers in the ovary of adult golden hamsters, M. auratus providing further insight into the regulation of female reproductive seasonality in a long-day breeder. © 2021 Elsevier Inc.