Endocrine Abstracts

Context: Recurrent Pregnancy Loss (RPL), defined as two or more consecutive pregnancy losses, is a serious reproductive problem, affecting 1–5 per cent of reproductive-age women. Although a high percentage (7.46%) of RPL cases are reported from India, scanty reports are available on the molecular mechanisms associated with RPL susceptibility in the population of the north-eastern state of Assam. Hormonal imbalances are a major cause of recurrent pregnancy loss. Recent studies indicate that estrogen plays a crucial role throughout pregnancy in fetal development, utero-placental blood flow, and implantation.

Objective: This work proposes to elucidate the role of alterations in the estrogen signalling pathway in the pathogenesis of RPL in the population of Assam. It would have therapeutic significance in atleast a sub-population of idiopathic RPL patients.

Methods: RPL patients who had undergone three or more spontaneous miscarriages (n=21) and medically terminated pregnancies (MTP) cases (n=35) were enrolled for this study. Biochemical level of estrogen in RPL patients and MTP cases was studied by ELISA. This was followed by transcript level study of differential expression of its receptors, ERα and ERβ by real time PCR method, and further validation at the protein level using immunofluorescence.

Results: The ELISA results indicated a higher level of estrogen in the RPL cases (5.03 ± 1.52 pg/ml) when compared with the MTP cases (3.6 ± 2.2 pg/ml) (P<0.020). The mRNA expression of the ER isoforms, ERα (0.08 ± 0.11 fold change) and ERβ (0.07 ± 0.09 fold change) was found to be downregulated in the RPL cohort compared to MTP. ERα, being the more functionally important receptor for estrogen-mediated signal transduction, its protein expression was also validated through immunofluorescence (IF). The IF results showed sporadic expression of ERα protein in both the MTP as well as RPL cases, with a sharp downregulation or even no expression of the receptors in the RPL product of conception (POC) tissues. However, correlation analysis did not show any significant correlation between these factors (P>0.05).

Conclusion: The results indicate the possible role of estrogen receptor expression that may be involved with RPL pathogenesis in the study population. However, the findings of this pilot study require validation in a larger sample size for therapeutic implementation.