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

L Bpm 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 Jm Broekmans; R J T van Golde; M Zamani Esteki; A Romano

doi:10.1530/RAF-23-0065

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

L Bpm 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 Jm Broekmans, R J T van Golde, M Zamani Esteki, A Romano

^*Corresponding author for this work

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Abstract

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 < 0.05 and log fold change >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.

Original language	English
Article number	e230065
Number of pages	14
Journal	Reproduction & fertility
Volume	4
Issue number	4
Early online date	1 Nov 2023
DOIs	https://doi.org/10.1530/RAF-23-0065
Publication status	Published - 13 Dec 2023

Keywords

HSD17B1
IVF
endometrium
implantation
oestrogen
receptivity

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Stevens Brentjens, L. B., Obukhova, D., Delvoux, B., den Hartog, J. E., Bui, B. N., Mol, F., de Bruin, J. P., Besselink, D., Teklenburg, G., Morgan, F., Baker, M., Broekmans, F. J., van Golde, R. J. T., Esteki, M. Z., & Romano, A. (2023). Local production of 17β-oestradiol in the endometrium during the implantation window: a pilot study. Reproduction & fertility, 4(4), Article e230065. https://doi.org/10.1530/RAF-23-0065

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

abstract = "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 < 0.05 and log fold change >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.",

keywords = "HSD17B1, IVF, endometrium, implantation, oestrogen, receptivity",

author = "{Stevens Brentjens}, {L Bpm} and D Obukhova and B Delvoux and {den Hartog}, {J E} and Bui, {B N} and F Mol and {de Bruin}, {J P} and D Besselink and G Teklenburg and F Morgan and M Baker and Broekmans, {F Jm} and {van Golde}, {R J T} and Esteki, {M Zamani} and A Romano",

note = "Publisher Copyright: {\textcopyright} 2023 the author(s) Published by Bioscientifica Ltd.",

year = "2023",

month = dec,

day = "13",

doi = "10.1530/RAF-23-0065",

language = "English",

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Stevens Brentjens, LB, Obukhova, D, Delvoux, B, den Hartog, JE, Bui, BN, Mol, F, de Bruin, JP, Besselink, D, Teklenburg, G, Morgan, F, Baker, M, Broekmans, FJ, van Golde, RJT, Esteki, MZ & Romano, A 2023, 'Local production of 17β-oestradiol in the endometrium during the implantation window: a pilot study', Reproduction & fertility, vol. 4, no. 4, e230065. https://doi.org/10.1530/RAF-23-0065

TY - JOUR

T1 - Local production of 17β-oestradiol in the endometrium during the implantation window

T2 - a pilot study

AU - Stevens Brentjens, L Bpm

AU - Obukhova, D

AU - Delvoux, B

AU - den Hartog, J E

AU - Bui, B N

AU - Mol, F

AU - de Bruin, J P

AU - Besselink, D

AU - Teklenburg, G

AU - Morgan, F

AU - Baker, M

AU - Broekmans, F Jm

AU - van Golde, R J T

AU - Esteki, M Zamani

AU - Romano, A

PY - 2023/12/13

Y1 - 2023/12/13

N2 - 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 < 0.05 and log fold change >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.

AB - 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 < 0.05 and log fold change >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.

KW - HSD17B1

KW - IVF

KW - endometrium

KW - implantation

KW - oestrogen

KW - receptivity

UR - http://www.scopus.com/inward/record.url?scp=85180008130&partnerID=8YFLogxK

U2 - 10.1530/RAF-23-0065

DO - 10.1530/RAF-23-0065

M3 - Article

C2 - 37962510

SN - 2633-8386

VL - 4

JO - Reproduction & fertility

JF - Reproduction & fertility

IS - 4

M1 - e230065

ER -

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

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