Understanding Pregnancy with PCOS

Monika R, PSG College of Technology, Coimbatore

Polycystic ovary syndrome is a common endocrine and metabolic disorder affecting approximately 4–18% of reproductive-aged women. It is characterized by hyperandrogenism and chronic anovulation. PCOS is related to an increased risk for metabolic complications, including type 2 diabetes, dyslipidemia, hypertension, and cardiovascular disease. Also, children of mothers with PCOS have an increased risk of autism. 

In humans, hormonal disturbances such as hyperandrogenism are considered important for developing PCOS. This androgen excess may exert metabolically harmful effects on adipose tissue (AT). Subcutaneous abdominal AT is extremely related to anovulation in women with obesity and infertility. AT even have pivotal roles in the metabolism of steroid family genes (sex steroid, mineralocorticoids, glucocorticoids), involved in AT’s steroidogenesis in women with PCOS. Yet there are not many studies conducted on the gene expressions in AT between women with and without PCOS.

However, recently a case study was conducted by researchers supported by Royan Institute and Islamic Azad University, Science and Research Branch, Tehran, Iran, to determine the difference in gene expressions associated with steroidogenesis in abdominal subcutaneous AT of PCOS and non-PCOS pregnant women.

Do gene expressions in AT differ between PCOS and non-PCOS pregnant women?

Neda Emami, the lead author of the study and Faculty of Science at Islamic Azad University,  said, “Our objectives were to finalize the differences between mRNA expression levels of key steroid converting enzymes associated with steroidogenesis in subcutaneous AT of PCOS and non-PCOS pregnant women”.

“For the current study, we enrolled 12 pregnant women with PCOS (case) and 36 non-PCOS pregnant women (control) in 1:3 ratio, with both age- and BMI-matched undergoing cesarean delivery,” said Neda Emami. He also added that by using quantitative real-time PCR, they investigated the expressions of 15 genes associated with steroidogenesis in abdominal subcutaneous AT.

Genes related to steroidogenesis

• The initial phase of steroidogenesis – Involves the steroidogenic acute regulator (STAR) and cytochrome P450 monooxygenase (CYP11A1) genes. 
• Glucocorticoids metabolism – 17α-hydroxylase (CYP17A1) and β-Hydroxysteroid dehydrogenase (HSD3B1, HSD3B2, HSD11B1, and HSD11B2) genes are involved in cortisol metabolism, whose profile is regulated by glucocorticoids metabolism. 
• Mineralocorticoids metabolism – The steroid 21-hydroxylase (CYP21A2) gene is involved. 
• Sex steroid metabolism – Involves aromatase cytochrome P450 (CYP19A1), and 17β-Hydroxysteroid dehydrogenases (HSD17B) with families (1, 2, 3, 5, 7, and 12) genes.

The difference in gene expression between PCOS and non-PCOS pregnant women

The levels of mRNA in subcutaneous AT samples of PCOS relative to non-PCOS (ns.: non-significant), according to the study, is given below:

From the case study, Neda Emami and his colleagues found that women with PCOS showed significantly higher mRNA levels of genes liable for the initial phase of steroidogenesis (STAR and CYP11A1) and glucocorticoid metabolism (CYP17A1, HSD11B1, and HSD11B2) than non-PCOS; and there was no significant difference in the mRNA levels of genes accountable for glucocorticoid metabolism (HSD3B1 and HSD3B2) and sex steroids except HSD17B2. But most of the sex steroid-converting genes were highly expressed on the day of delivery in subcutaneous AT. The expression of the gene responsible for mineralocorticoid metabolism CYP21A2 in non-PCOS was fourfold higher than those of women with PCOS.   “No significant differences were detected concerning age, BMI (prior pregnancy and at delivery day), gestational period, and parity between the two groups,” said Emami.

Importance of this kind of case study 

This research displays the acute reduction of CYP21A2 mRNA for PCOS women in AT which further confirms gene expression disorders in mineralocorticoid metabolism for PCOS pregnant women. This achievement also opens the horizon for more exploration regarding AT roles in cortisol metabolism in mothers with PCOS. This study only indicates the alterations in gene expressions involved in glucocorticoids and mineralocorticoids metabolism of pregnant women with PCOS, but further studies with regards to functional activity remain required. The pathogenesis and treatment of PCOS also are yet unclear. The efforts to display the specific cellular mechanisms of PCOS will contribute to novel treatments and control methods for this complex syndrome.

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Source: Emami, N., Moini, A., Yaghmaei, P., Akbarinejad, V., Shahhoseini, M., & Alizadeh, A. (2021). Differences in expression of genes related to steroidogenesis in abdominal subcutaneous adipose tissue of pregnant women with and without PCOS; a case-control study. BMC Pregnancy and Childbirth, 21(1), 490. https://doi.org/10.1186/s12884-021-03957-5

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About the author: Monika Raman is an undergraduate student pursuing her final year B. Tech in Biotechnology. She is an enthusiastic Biotech student aspiring for an opportunity to develop skills and grow professionally in the research field. Extremely motivated and possess strong interpersonal skills.