Reproduction and Fertility (Dec 2023)

Local production of 17β-oestradiol in the endometrium during the implantation window: a pilot study

  • L B P M Stevens Brentjens,
  • D Obukhova,
  • B Delvoux,
  • J E den Hartog,
  • B N Bui,
  • F Mol,
  • J P de Bruin,
  • D Besselink,
  • G Teklenburg,
  • F Morgan,
  • M Baker,
  • F J M Broekmans,
  • R J T van Golde,
  • M Zamani Esteki,
  • A Romano

DOI
https://doi.org/10.1530/RAF-23-0065
Journal volume & issue
Vol. 4, no. 4
pp. 1 – 14

Abstract

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Sex steroids are converted to bioactive metabolites and vice versa by endometrial steroid-metabolising enzymes. Studies indicate that alterations in this metabolism might affect endometrial receptivity. This pilot study determined whether the endometrial formation and inactivation of 17β-oestradiol differed between the supposedly embryo-receptive endometrium and non-receptive endometrium of women undergoing IVF/intracytoplasmic sperm injection (ICSI). Endometrial biopsies were obtained from IVF/ICSI patients 5–8 days after ovulation in a natural cycle, prior to their second IVF/ICSI cycle with fresh embryo transfer (ET). Endometrial biopsies from patients who achieved clinical pregnancy after fresh ET (n = 15) were compared with endometrial biopsies from patients that did not conceive after fresh ET (n = 15). Formation of 17β-oestradiol (oxidative 17β-hydroxysteroid dehydrogenases (HSDs)), oestrone (reductive HSD17Bs) and inhibition of HSD17B1 activity were determined by high-performance liquid chromatography. The endometrial transcriptome was profiled using RNA sequencing followed by principal component analysis and differentially expressed gene analysis. The false discovery rate-adjusted P 0.5 were selected as the screening threshold. Formation and inactivation of 17β-oestradiol resulted similar between groups. Inhibition of HSD17B1 activity was significantly higher in the non-pregnant group when only primary infertile women (n = 12) were considered (27.1%, n = 5 vs 16.2%, n = 7, P = 0.04). Gene expression analysis confirmed the presence of HSD17B1 (encoding HSD17B1), HSD17B2 (encoding HSD17B2) and 33 of 46 analysed steroid metabolising enzymes in the endometrium. In the primary infertile subgroup (n = 10) 12 DEGs were found including LINC02349 which has been linked to implantation. However, the exact relationship between steroid-metabolising enzyme activity, expression and implantation outcome requires further investigation in larger, well-defined patient groups.

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