Significance of Hyperhomocysteinemia in Immediate As Well As Long-Term Health Risk/s in Women with Polycystic Ovary Syndrome: a Probabilistic Model Using Dynamic Bayesian Network Analysis

Chakraborty, Pratip; Mitra, Imon; Kalapahar, S; Sharma, Sunita; Chattopadhyay, Ratna; Chakravarty, Baidyanath

doi:10.1007/s43032-022-01028-4

Cited by 3 publications

(2 citation statements)

References 27 publications

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“…PCOS is commonly associated with metabolic and cardiovascular complications, and IR is the potential pathogenetic mechanism for both (22,24,25). Insulin resistance and compensatory hyperinsulinemia are one of the most important events in the pathogenesis of PCOS.…”

Section: Discussionmentioning

confidence: 99%

Hyperhomocysteinemia and pregnancy outcomes in women with polycystic ovary syndrome: A case-control study

Asanidze

Kristesashvili

Parunashvili

et al. 2023

IJRM

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Background: One of the reproductive medicine challenges is to determine the role of hyperhomocysteinemia in the pathogenesis of polycystic ovary syndrome (PCOS), especially in women with recurrent pregnancy loss (RPL). Objective: Determine the correlation between hyperhomocysteinemia and pregnancy outcome in women with PCOS. Materials and Methods: This case-control study involved 245 women (20-30 yr) and was conducted in Georgia, Tbilisi from 2019-2022. Of these, 175 were women with PCOS (study group) and 70 were healthy women (control group). Women with PCOS were divided into group I with RPL (n = 90), and group II with live births (n = 85). Group I was divided into subgroups A and B with and without insulin resistance. The investigation measured homocysteine (Hcy), follicle-stimulating, luteinizing, anti-Mullerian hormones, total and free testosterone were determined. To determine the ovarian volume and antral follicle count, participants also underwent an ultrasound examination. Results: In women with PCOS, the average Hcy level was significantly higher than in the controls, p < 0.05. In group I, the average Hcy level was significantly higher than in group II and controls, p < 0.05. There was no significant difference in average Hcy level between group II and controls. The average Hcy level in group I, subgroup A was significantly higher than in subgroup B, p < 0.05. The average total, free testosterone levels, and homeostatic model assessment-insulin resistance levels (HOMA-IR) in group I was significantly higher than in group II and controls. HOMA-IR in group II and controls did not differ significantly. The average anti-Mullerian hormone levels in women with PCOS were significantly higher than controls, p < 0.05. No significant difference was observed in average anti-Mullerian hormone level, ovarian volume, antral follicle count, and body mass index between the comparison groups of PCOS. In group I, a positive correlation between Hcy with HOMA-IR was detected. Conclusion: Serum Hcy levels are elevated in women with PCOS and RPL, which correlates with their insulin resistance status. Key words: Polycystic ovary syndrome, Hyperhomocysteinemia, Recurrent abortion, Insulin resistance.

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Section: Discussionmentioning

confidence: 99%

Hyperhomocysteinemia and pregnancy outcomes in women with polycystic ovary syndrome: A case-control study

Asanidze

Kristesashvili

Parunashvili

et al. 2023

IJRM

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“…Referring to our previous studies [2,22] in hyperhomocysteinemic spontaneous abortion patients, a pregnant rat model was prepared exposed to high homocysteine intake, in which fetal survival was examined during mid to late gestation. Recently, our group has demonstrated the role of HHcy in long-term goals of polycystic ovary syndrome (PCOS) [23]. Pregnancy loss in PCOS is a much-discussed issue; HHcy being the centerpiece of USM in INDIA [2], we concentrated on the pathology to dissect the mechanism responsible for HHcy-mediated USM.…”

Section: Introductionmentioning

confidence: 99%

Attenuation of placental pyruvate kinase M2 promotes oxidative imbalance and enhances inflammatory- apoptosis cross talk in rats with hyperhomocysteinemia associated pregnancy loss

Chakraborty

Chatterjee

et al. 2022

Preprint

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10-15% of clinically recognized pregnancies end in miscarriage. Hyperhomocysteinemia in pregnant women has been associated with deep venous thrombosis, recurrent miscarriage, preeclampsia to name a few. Impaired placental function due to overt oxidative stress is one of the key mechanisms in development of pregnancy loss. Paucity of pathway–based microarray approach in embryonic–endometrial communication warrants elucidation of distinct profile of miRNAs in hyperhomocysteinemia-associated pregnancy loss (HAPL). Hyperhomocysteinemia was induced at a dose of 100mg/kg body-weight/day for D1-D18 of pregnancy. Placental histology by haematoxylin-eosin staining documented thrombus with reduced area of spongiotropoblasts in chorionic plate vessel. Placental mRNA was subjected to microarray analysis followed by pathway-analysis using Ingenuity Pathway Analysis (IPA). Genes involved in reproductive physiology, inflammatory pathways, immune responses, homocysteine metabolism, glucose metabolism, and oxidative stress were differentially expressed in HAPL. 21 pathways documented by IPA, were skewed to 10 by recursive feature elimination highlighting possible deregulation/s. Expression/s was re-confirmed by quantitative real- time PCR (qRT-PCR), western blot and flow cytometric analysis (FACS). Nine priori molecules (PKM2, AKT, PI3K, NF-κB, COX-2, sflt-1, HIF-1α, bax, caspase 9) were specifically modulated in HAPL as demonstrated by protein and mRNA expression. A parallel increase in insulin signaling (PI3K+,AKT+), inflammation (COX2+,NF-κB+), hypoxia (sflt-1+,HIF-1α+), apoptosis (bax+,caspase9+) with concomitant decrease in pyruvate kinase M2 in hyperhomocysteinemic placental cells by FACS with CD56, a marker for pregnancy loss was documented. The findings provide evidence that an oxidative stress-mediated placental damage perhaps represents the pathogenesis of HAPL, which may explore pathway-based therapeutic options for recurrent miscarriage.10–15% of clinically recognized pregnancies end in miscarriage. Hyperhomocysteinemia in pregnant women has been associated with deep venous thrombosis, recurrent miscarriage, preeclampsia to name a few. Impaired placental function due to overt oxidative stress is one of the key mechanisms in development of pregnancy loss. Paucity of pathway–based microarray approach in embryonic–endometrial communication warrants elucidation of distinct profile of miRNAs in hyperhomocysteinemia-associated pregnancy loss (HAPL). Hyperhomocysteinemia was induced at a dose of 100mg/kg body-weight/day for D1-D18 of pregnancy. Placental histology by haematoxylin-eosin staining documented thrombus with reduced area of spongiotropoblasts in chorionic plate vessel. Placental mRNA was subjected to microarray analysis followed by pathway-analysis using Ingenuity Pathway Analysis (IPA). Genes involved in reproductive physiology, inflammatory pathways, immune responses, homocysteine metabolism, glucose metabolism, and oxidative stress were differentially expressed in HAPL. 21 pathways documented by IPA, were skewed to 10 by recursive feature elimination highlighting possible deregulation/s. Expression/s was re-confirmed by quantitative real- time PCR (qRT-PCR), western blot and flow cytometric analysis (FACS). Nine priori molecules (PKM2, AKT, PI3K, NF-κB, COX-2, sflt-1, HIF-1α, bax, caspase 9) were specifically modulated in HAPL as demonstrated by protein and mRNA expression. A parallel increase in insulin signaling (PI3K+,AKT+), inflammation (COX2+,NF-κB+), hypoxia (sflt-1+,HIF-1α+), apoptosis (bax+,caspase9+) with concomitant decrease in pyruvate kinase M2 in hyperhomocysteinemic placental cells by FACS with CD56, a marker for pregnancy loss was documented. The findings provide evidence that an oxidative stress-mediated placental damage perhaps represents the pathogenesis of HAPL, which may explore pathway-based therapeutic options for recurrent miscarriage.

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Homocysteine, vitamin B12, and folate circulating levels in women with and without polycystic ovary syndrome: A systematic review and meta-analysis

Ulloque-Badaracco,

Al-kassab-Córdova,

Hernández-Bustamante

et al. 2024

Womens Health (Lond Engl)

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Background: Some studies have reported that homocysteine, vitamin B12, and folic acid levels are associated with polycystic ovary syndrome (PCOS), whereas other studies yielded controversial results. Objectives: This study aimed to systematize the available evidence of homocysteine, vitamin B12, and folate levels in women with and without PCOS. Design: Systematic review and meta-analysis Data Sources and Methods: A systematic search without language restrictions was performed on PubMed, Ovid/Medline, Scopus, Embase, and Web of Science. In addition, the reference lists of the selected studies were reviewed. The Newcastle–Ottawa Scale was employed to evaluate the quality of studies. The means and standard deviations of the outcomes were pooled as standardized mean differences (SMDs) with 95% confidence intervals (CI). Furthermore, the DerSimonian and Laird method was employed for the quantitative synthesis. Results: A total of 75 studies met the eligibility criteria for at least one outcome. Patients with PCOS had higher circulating homocysteine levels than those without (SMD: 0.82; 95% CI: 0.62–1.02, n = 70 studies, p < 0.001). This trend remained in the sensitivity and subgroup analyses by world regions of studies, assay methods, and insulin resistance. No significant differences were observed in circulating vitamin B12 (SMD: −0.11; 95% CI: −0.25 to 0.03; n = 17 studies, p = 0.13) and folate levels (SMD: −0.2; 95% CI: −0.68 to 0.27; n = 17 studies, p = 0.41) between patients with and without PCOS. Conclusions: (i) Patients with PCOS exhibited significantly higher homocysteine levels than those without, and (ii) no significant differences were observed in both vitamin B12 and folate levels in women with and without PCOS. Registration: PROSPERO ID (CRD42023432883)

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Significance of Hyperhomocysteinemia in Immediate As Well As Long-Term Health Risk/s in Women with Polycystic Ovary Syndrome: a Probabilistic Model Using Dynamic Bayesian Network Analysis

Cited by 3 publications

References 27 publications

Hyperhomocysteinemia and pregnancy outcomes in women with polycystic ovary syndrome: A case-control study

Hyperhomocysteinemia and pregnancy outcomes in women with polycystic ovary syndrome: A case-control study

Attenuation of placental pyruvate kinase M2 promotes oxidative imbalance and enhances inflammatory- apoptosis cross talk in rats with hyperhomocysteinemia associated pregnancy loss

Homocysteine, vitamin B12, and folate circulating levels in women with and without polycystic ovary syndrome: A systematic review and meta-analysis

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