Placental dysfunction reflects endocrine impairment and trophoblast alterations in polycystic ovarian syndrome

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that contributes to pregnancy complications like Intra Uterine Growth Restriction (IUGR), leading to compromised foetal outcome. Although maternal metabolic and hormonal imbalances are well-established in PCOS, the specific molecular alterations within the placenta and its outcome remains poorly explored. This study aimed to characterize key molecular signaling alterations in PCOS placentae with respect to steroid hormone receptors, trophoblast lineage specification, along with their structural alterations. To understand the above alterations, PCOS rodent mothers were developed using letrozole treatment for 21days daily orally, following which induction of pregnancy and those pregnant animals were sacrificed at GD18. Tissues were subjected to expression levels of steroidal and placental cell markers using transcriptomic and protein expression, along with morphometric and histological analysis, correlated with hormone profile. Histological analysis of GD 18 PCOS placenta exhibited a reduction in labyrinth zone, with an increased AR expression, along with downregulation of PR, ER ɑ and ER β, indicating an altered steroidal status. Moreover, dysregulation of genes such as Phlda2, Tpbpa, Pcdh12, Prl3b1, CDX2, GCM1, and GATA2 along with reduced expression of SynA, Syn B were observed suggesting an impaired trophoblast differentiation, vascular development, and immune tolerance. Additionally, elevated expressions of Flt4, H2K^d and IFN gamma suggested compensatory mechanisms attempting to offset placental dysfunction. This study clearly indicates maternal PCOS pathophysiology effects placental development by altering the morphology, along with abnormal hormonal homeostasis, contributing to impaired differentiation. These findings underscore the importance of targeting placental pathways in the management of PCOS-related pregnancy outcomes.