The Apolipoprotein A-I Level Is Downregulated in the Granulosa Cells of Patients with Polycystic Ovary Syndrome and Affects Steroidogenesis (original) (raw)
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Molecular and Cellular Endocrinology, 2019
Introduction Aberrant function of granulosa cells has been implicated in the pathophysiology of PCOS. Materials & methods GL cells were collected during oocyte retrieval for IVF/ICSI. RT-qPCR was used to compare gene expression between 12 control women, 12 with ovulatory PCO and 12 with anovulatory PCOS. To examine which genes are directly regulated by androgens, GL cells from an additional 12 control women were treated in-vitro with 10nM dihydrotestosterone (DHT). Results Women with PCOS showed reduced expression of CYP11A1 3-fold (p=0.005), HSD17B1 1.8-fold (p=0.02) and increased expression of SULT1E1 7-fold (p=0.0003). Similar results were seen in ovulatory women with PCO. GL cells treated with 10nM DHT showed a 4-fold (p=0.03) increase in expression of SULT1E1 and a 5-fold reduction in SRD5A1 (p=0.03). Conclusions These findings support the notion that aberrant regulation of steroid metabolism or action play a part in ovarian dysfunction in PCOS
Human Reproduction, 1996
We evaluated the immunolocalization of the steroidogenic enzymes involved in the production of ovarian steroids, including the cholesterol side-chain cleavage enzyme (P450scc), 3p"-hydroxysteroid dehydrogenase (HSD), 17ahydroxylase (P450cl7) and aromatase (P450arom), oestrogen receptor (ER) and androgen receptor (AR), a steroidogenic transcription factor, Ad4-binding protein (Ad4BP) and a cell cycle-related nuclear antigen, Ki67, in five patients with polycystic ovarian syndrome (PCOS). Results were compared with those from normal cycling human ovaries to study in situ ovarian steroidogenesis and cell proliferation in polycystic ovaries (PCO). We classified the follicles morphologically according to the development of granulosa cells: type A, more than four layers (n = 7); type B, one to three layers (n = 11); and type C, theca interna cells only (n = 21). ER and P450arom were not observed in any of the follicles examined. In type A follicles, P450scc, 3P-HSD, P450cl7, AR and Ad4BP were observed in theca cells in all seven follicles examined, but the granulosa cells were positive only for Ad4BP (4/7) and AR (7/7). These immunohistolocalization patterns resembled those in non-selected antral follicles of normally cycling human ovaries. In theca cells from types B and C follicles, follicles positive for the steroidogenic enzymes, AR and Ad4BP were decreased in number. There were no significant differences between types A and B PCO follicles in the Ki67 labelling index of granulosa or theca cells, and between PCO and antral follicles from normally cycling human ovaries. Data demonstrate that the follicles of PCO are by no means atretic and are actively involved in both steroidogenesis and cell proliferation. The absence of ER and aromatase expression in the granulosa cells of PCO may be important in abnormal follicular development in patients with PCOS.
Proteomic analysis of human ovaries from normal and polycystic ovarian syndrome
MHR: Basic science of reproductive medicine, 2007
Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility, affecting 5-10% of females of reproductive age. Currently, little is known about the changes in whole proteins between PCOS and normal ovaries. In the present study, a proteomic approach comprised two-dimensional gel electrophoresis (2DE) analysis and mass spectroscopy was used to identify proteins and examine expression patterns in three PCOS and normal ovaries. One hundred and ten protein spots were separated and showed different intensities between PCOS and normal ovaries. Sixty-nine proteins associated with cellular metabolism and physiological process were identified from 72 spots. Fifty-four proteins were up-regulated in PCOS ovaries and 15 other proteins were up-regulated in normal ovaries. These data demonstrate, for the first time, the complexity in the regulation of ovarian protein expression in human PCOS, and will provide important insight for a better understanding of the pathogenetic mechanisms underlying this clinical disorder.
The Journal of Clinical Endocrinology and Metabolism, 2002
A defining characteristic of dominant follicles is high estradiol concentrations. Abnormal expression of estrogen receptors (ERs) could contribute to poor follicular development and ovulatory failure in polycystic ovary syndrome (PCOS). The aim of this study was to determine whether there are differences in ER␣ and ER expression in granulosa cells (GC) and theca cells (TC) from women with PCOS, compared with regularly cycling women. GC and TC were obtained by microdissection from 12 polycystic and 23 normal ovaries. ER␣ and ER mRNA and protein expression were measured by semiquantitative RT-PCR and Western blot, respectively. In control ovaries, both GC and TC ER␣ mRNAs were higher in small antral (SA) than in dominant follicles. ER␣ mRNA was similar in PCOS and size-matched control follicles. In control follicles, ER␣ protein concentrations were higher in GC than in TC. In GC, the ER␣ concentrations were comparable among SA, dominant, and PCOS follicles. In TC, ER␣ concentrations were lower in dominant follicles but were markedly increased in PCOS. In control ovaries, GC and TC expression of ER mRNA was higher in SA, compared with dominant follicles. In PCOS, ER mRNA was intermediate between SA and dominant follicles in both GC and TC. In GC, the ER protein concentrations followed the same pattern as mRNA expression; but in TC ER, protein in PCOS was equivalent to that in dominant follicles. The results of this study demonstrate that there are significant alterations in the expression of ER␣ and ER in PCOS that may be related to abnormal follicular development. (J Clin Endocrinol Metab 87: 5532-5538, 2002)
Immunohistochemical study of steroidogenesis and cell proliferation in polycystic ovarian syndrome
Human reproduction (Oxford, England), 1996
We evaluated the immunolocalization of the steroidogenic enzymes involved in the production of ovarian steroids, including the cholesterol side-chain cleavage enzyme (P450scc), 3beta-hydroxysteroid dehydrogenase (HSD), 17alpha-hydroxylase (P450c17) and aromatase (P450arom), oestrogen receptor (ER) and androgen receptor (AR), a steroidogenic transcription factor. Ad4-binding protein (Ad4BP) and a cell cycle-related nuclear antigen, Ki67, in five patients with polycystic ovarian syndrome (PCOS). Results were compared with those from normal cycling human ovaries to study in situ ovarian steroidogenesis and cell proliferation in polycystic ovaries (PCO). We classifed the follicles morphologically according to the development of granulosa types: type A, more than four layers (n = 7); type B, one to three layers (n = 11); and type C, theca interna cells only (n = 21). ER and P450arom were not observed in any of the follicles examined. In type A follicles, P450scc, 3beta-HSD, P450c17, AR a...
The Journal of Clinical Endocrinology & Metabolism, 2019
Context Polycystic ovary syndrome (PCOS) is the most common cause of anovulation. A key feature of PCOS is arrest of follicles at the small- to medium-sized antral stage. Objective and Design To provide further insight into the mechanism of follicle arrest in PCOS, we profiled (i) gonadotropin receptors; (ii) characteristics of aberrant steroidogenesis; and (iii) expression of anti-Müllerian hormone (AMH) and its receptor in granulosa cells (GCs) from unstimulated, human small antral follicles (hSAFs) and from granulosa lutein cells (GLCs). Setting GCs from hSAFs were collected at the time of cryopreservation of ovarian tissue for fertility preservation and GLCs collected during oocyte aspiration before in vitro fertilization/intracytoplasmic sperm injection. Participants We collected hSAF GCs from 31 women (98 follicles): 10 with polycystic ovaries (PCO) and 21 without. GLCs were collected from 6 women with PCOS and 6 controls undergoing IVF. Main Outcome Measures Expression of the...
Fertility and Sterility, 2010
To compare steroid concentrations and steroid product-to-precursor ratios in ovarian follicular fluid (FF) from women with polycystic ovary syndrome (PCOS) and from regularly menstruating women in their early follicular phase, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Polycystic ovary syndrome involves abnormal regulation of the steroidogenic enzymes, leading to arrest of follicle development. Case-control study. University hospital clinic. Follicular fluid from size-matched ovarian follicles (5-8 mm) in 27 nonstimulated women with PCOS and in 21 women without PCOS was sampled. Thirteen steroids were quantitated from 40 μL of FF, using LC-MS/MS. None. Concentrations of steroids in the FF and product-to-precursor ratios (enzyme activity) were compared between the groups. In women with PCOS, ovarian FF contained higher concentrations of individual and total androgens, lower individual and total estrogens (E), and a lower total E-to-androgen ratio, compared with regularly menstruating women. The product-to-precursor concentration ratios indicated higher CYP17-linked and lower CYP19-linked (aromatase) enzyme activity. Receiver operating characteristic plots indicated the early CYP17 step (17-OH5P/5P) being highly important for the prevalence of PCOS (c=0.95). The women with PCOS had higher ovarian CYP17-linked and lower CYP19-linked (aromatase) enzyme activity, confirming previous data. Multiple steroid assessments from minute volumes including FF from nonstimulated ovaries, using LC-MS/MS, might be useful in research, clinical endocrinology, and in IVF.
The Journal of Clinical Endocrinology & Metabolism, 2001
Recent data suggest that steroidogenic enzyme messenger ribonucleic acids (mRNAs) may be overexpressed in thecal cells, and LH receptors may be prematurely expressed in granulosa cells in women with polycystic ovaries. The purpose of this study was to determine whether there is abnormal gene expression in thecal and granulosa cells from polycystic ovaries. Ovarian tissue specimens were obtained from 12 women with PCOS and 24 regularly cycling control women. The granulosa cells and the theca interna were microdissected from individual follicles. LH receptor, steroidogenesis acute regulatory protein (StAR), cholesterol side-chain cleavage cytochrome P450 (CYP11A), and 17␣-hydroxylase/C 17-20 lyase cytochrome P450 (CYP17) mRNAs were measured by RT-PCR. There was no difference between 3-to 7-mm control follicles and dominant follicles with respect to LH receptor mRNA expression in either thecal or granulosa
Objective: To explore the level of apolipoprotein A1 expression in human endometrial tissues in women with polycystic ovary syndrome compared to fertile women. Patients and Methods: This was a cross sectional study performed at Ain Shams University Maternity Hospital, over a 2-year period, between Jan 2014 and Jan 2016, and included 80 women divided into two groups. Group I (n=40) with polycystic ovary syndrome who were presented at the infertility clinic and group II (n=40) fertile women who were presented due to any cause other than infertility as a control group. All women were scheduled for endometrial sampling by Endosampler. Participant ages ranged from 20 to 35 years. A written informed consent was obtained from all women before participation. Endometrial apolipoprotein A1 was investigated using ELIZA. Samples were obtained from all patients in the proliferative phase (just before ovulation when the dominant follicle is 20 mm) and secretory phase (5 days after the 1st sample)