Dysregulation of collagen expression in peri‐implantation endometrium of women with high ovarian response

Abstract

Aim To analyze the effects of high ovarian response on endometrial collagen synthesis and related gene expression during the peri‐implantation period in patients undergoing in vitro fertilization‐embryo transfer. Methods Peripheral blood and endometrial biopsies were obtained from infertile women on day 6 after oocytes retrieval or ovulation in 16 stimulated cycles (SC) and 16 natural cycles (NC) respectively. Serum estrogen (E2), progesterone (P4), histological staging, endometrial collagen, matrix metalloproteinases (MMP2, 9) and tissue inhibitors of metalloproteinases (TIMP1, 3) were assayed. Results Serum levels of both E2 and P4 were significantly higher in the SC group than those in the NC group. All endometrial samples were in the secretory phase. The collagen in the stroma of the SC group was more dense and higher than that in the NC group. MMP2 and MMP9 were detected significantly lower in the SC group than those in the NC group, while TIMP1 and TIMP3 were significantly higher. MMP2, 9 expressions are increased by estrogen and reduced by progesterone in dose‐dependent manner through estrogen receptor and progesterone receptor. Correspondingly, TIMP1, 3 expressions decreased by estrogen dose‐dependently while progesterone played the opposite role. Conclusion High levels of P4 could stimulate excessive synthesis of collagen in peri‐implantation endometrium of women with high ovarian response, and the mechanisms may be related to the decrease of MMP2, 9 and the increase of TIMP1, 3 through P4 receptor.

Specific locations and amounts of denatured collagen and collagen-specific chaperone HSP47 in the oviducts and uteri of old cows as compared with those of heifers

“…However, little is known about the exact pathophysiological mechanisms in oviducts and uteri. Collagen, one of the most abundant extra-cellular matrix (ECM) proteins, exerts a critical role in successful pregnancies, and abnormal collagen expression is associated with recurring miscarriages in women (Li et al 2019, Shi et al 2020). The bovine endometrium, similar to that of other mammalians, changes morphologically throughout the oestrous cycle (Arai et al 2013).…”

The effects of multiple controlled ovarian hyperstimulation over a 2-year period on ovarian reserve and reactivity: a retrospective clinical study

“…Ovarian reactivity refers to the response of the ovary to GN during COH, and this is measured by GN dosage, ovulation induction time, number of eggs, and other indicators (9). At present, reports examining the effects of repeated COH on ovarian reactivity remain controversial.…”

Does the decrease in E2 levels between the trigger of ovulation and embryo transfer affect the reproductive outcome in IVF-ICSI cycles?

“…Implantation is the most important step in assisted reproductive technologies (ARTs), but the process is still poorly understood. However, it has been shown that implantation is strongly related to endometrial receptivity, which in turn is affected by serum estradiol (E2) and progesterone (P) levels ( 1 , 2 , 3 ) . The results clearly showed that very low or supraphysiological E2 levels have a negative impact on the reproductive outcome ( 4 , 5 ) .…”