title: Modulation of steroidogenic pathway in rat granulosa cells with subclinical Cd exposure and insulin resistance: an impact on female fertility.
abstract: Changes in lifestyle lead to insulin resistance (IR) in females ultimately predisposing them towards infertility. In addition, cadmium (Cd), an environmental endocrine disruptor, is reported for detrimental effects on granulosa cells, thus leading to ovarian dysfunction. A combination of these factors, lifestyle and environment, seems to play a role in etiology of idiopathic infertility that accounts for 50% amongst the total infertility cases. To address this issue, we made an attempt to investigate the extent of Cd impact on insulin-resistant (IR) granulosa cells. We exposed adult female Charles Foster rats to dexamethasone and confirmed IR condition by fasting insulin resistance index (FIRI). On treatment of IR rats with Cd, the preliminary studies demonstrated prolonged estrous cyclicity, decrease in serum estradiol concentrations, abnormal histology of ovary, and increased granulosa cell death. Further gene and protein expression studies of steroidogenic acute regulatory (StAR) protein, 17β-hydroxysteroid dehydrogenase (17β-HSD), and cytochrome P450 aromatase (CYP19A1) were performed. Protein expression studies demonstrated significant decrease in treated groups when compared with control. Study revealed that, in spite of the molecular parameters being affected at varied level, overall ovarian physiology is maximally affected in IR and Cd coexposed group, thus mimicking the condition similar to those prevailing in infertile females.
authors.affiliation: Department of Biochemistry, Faculty of Science, The M. S. University of Baroda, Vadodara, Gujarat 390 002, India.
authors.forename: Muskaan
authors.initials: M
authors.lastname: Belani
authors.affiliation: Department of Biochemistry, Faculty of Science, The M. S. University of Baroda, Vadodara, Gujarat 390 002, India.
authors.forename: Nupur
authors.initials: N
authors.lastname: Purohit
authors.affiliation: Department of Zoology, Faculty of Science, The M. S. University of Baroda, Vadodara, Gujarat 390 002, India.
authors.forename: Prakash
authors.initials: P
authors.lastname: Pillai
authors.affiliation: Gupta's Pathology Laboratory, Vadodara, Gujarat 390 002, India.
authors.forename: Sharad
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Biochemistry, Faculty of Science, The M. S. University of Baroda, Vadodara, Gujarat 390 002, India.
authors.forename: Sarita
authors.initials: S
authors.lastname: Gupta
mesh_terms: D000328:Adult; D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D003907:Dexamethasone / Q000633:toxicity; D004958:Estradiol / Q000378:metabolism; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D006107:Granulosa Cells / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics; D010053:Ovary / Q000187:drug effects; D010750:Phosphoproteins / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D007328:Insulin; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D002104:Cadmium; D011374:Progesterone; D004958:Estradiol; D003907:Dexamethasone; D005640:Follicle Stimulating Hormone