Induction of endometrial HOXA 10 gene expression by vitamin D and its possible influence on reproductive outcome of PCOS patients undergoing ovulation induction procedure

Abstract

Background and Objectives: Polycystic ovarian syndrome (PCOS) is one of the most common endocrinopathies in women frequently presenting with anovulatory infertility. Low successful pregnancy and live birth rates even after successful ovulation induction (OI) and in vitro fertilization (IVF) in these patients indicate that endometrial dysfunction may be another important factor contributing to infertility. Vitamin D acting through nuclear receptors induces the expression of various genes required for cell growth and differentiation and plays a crucial role in reproduction. Homeobox 10 (HOXA10) may be one of the potential targets for vitamin D action. HOXA10 gene product promotes the differentiation of endometrial cells, making the endometrium receptive for implantation. The present study was undertaken to determine the effect of circulating vitamin D levels on HOXA10 gene expression in endometrial tissues and its possible influence on the reproductive outcome of PCOS patients undergoing OI procedure. Materials and Methods: A prospective cohort study was conducted on 110 infertile PCOS patients. The patients were divided into two groups: Group 1: Vitamin D ≥20 ng/ml, Group 2: Vitamin D <20 ng/ml. Endometrial samples were obtained from 22 patients using pipelle biopsy, used to determine HOXA10 mRNA (messenger ribonucleic acid) expression by quantitative RT-PCR (reverse transcription-polymerase chain reaction) and protein expression by Western blotting. OI was performed using Clomiphene citrate or Letrozole from the 3rd day of the cycle, and patients were followed up for a maximum of five cycles. Attainment of successful pregnancy was considered a positive outcome.Results: Both the groups were similar in mean age and other endocrine parameters. Serum vitamin D levels were significantly low (P < 0.001), and BMI (body mass index) was significantly high (P = 0.032) in group 2 compared to group 1. Endometrial HOXA10 mRNA (by quantitative rtPCR) and protein expression (by western blotting) were significantly low in group 2 compared to group 1. The clinical pregnancy rate was low in group 2 (28.6%) compared to group 1 (42.3%), but this difference was not significant (P = 0.22). On regression analysis adjusted for age and BMI, vitamin D was an independent predictor of successful pregnancy after OI (P = 0.09). Conclusion: Circulating vitamin D levels influence the endometrial HOXA10 gene expression, and this may be reflected on the reproductive outcome of infertile PCOS patients undergoing OI.

Keywords

• hoxa 10
• ovulation induction
• polycystic ovarian syndrome
• vitamin d