Comprehensive molecular features of polycystic ovary syndrome revealed by transcriptome analysis of oocytes and cumulus cells

Abstract

PCOS is typically characterized by polycystic ovarian morphology, hyperandrogenism, ovulatory dysfunction and infertility. Furthermore, PCOS patients undergoing ovarian stimulation have more oocytes, however, poor quality of oocytes lead to lower fertilization and implantation rates, decreased pregnancy and increased miscarriage rates. Our study suggests that global gene expression and cell to cell interactions of oocytes and CCs are significantly altered in women with PCOS. Noticeably, genes related to microtubules such as TUBB8 and TUBA1C are abnormally highly expressed in PCOS oocytes, reducing oocyte quality. The pattern of transposable element expression distinguishes PCOS from Control oocytes, implying the role of transposable elements in the occurrence of PCOS.

Consequences of pathogenic tubulin-mutations on molecular motor proteins and their implications in tubulinopathies

“…Tuba1c, along with Tubb8, is over-expressed in PCOS oocytes where the MTs are defective along with general spindle defects potentially resulting in low-quality oocytes (Li et al, 2021). It was previously shown that Tubb8 is the predominant β-tubulin that is expressed only in primate oocytes and TUBB8 mutations result in oocyte maturation arrest, thereby resulting in female infertility .…”

“…Even though Tubb8 is also expressed in spermatozoa, the mutations do not render males infertile, but instead, the next female generation inherits infertility associated with the mutated copy of TUBB8 following the Mendelian pattern of inheritance . Recently, significant overexpression of Tubb8 has been seen in PCOS oocytes with defective MTs along with general spindle defects leading to overall low-quality oocytes (Li et al, 2021). TUBB8 mutations associated with female infertility are very commonly observed and there are more that 120 variants reported till date in infertile females (Appendix Table.…”