Significance of pro-angiogenic estrogen metabolites in normal follicular development and follicular growth arrest in polycystic ovary syndrome.

Study Question: Do alterations in pro- and anti-angiogenic estrogen metabolites in follicular fluid (FF) contribute to the follicular growth arrest and anovulation associated with polycystic ovary syndrome (PCOS)?

Summary Answer: FF of PCOS women with anovulation have reduced levels of pro-angiogenic estrogen metabolites (EMs) and vascular endothelial growth factor (VEGF) compared to that of fertile women with regular menstrual cycles, but exogenous gonadotropins increase the pro-angiogenic EMs and VEGF levels in PCOS women.

What Is Known Already: PCOS is characterized by the arrest of follicular development that leads to chronic anovulation. Follicular arrest is generally associated with elevated plasma levels of luteinizing hormone (LH), androgens and anti-Mullerian hormone (AMH).

Molecular modelling predicts that 2-methoxyestradiol disrupts HIF function by binding to the PAS-B domain.

An estradiol metabolite, 2-methoxyestradiol (2ME), has emerged as an important regulator of ovarian physiology. 2ME is recognized as a potent anti-angiogenic agent in clinical trials and laboratory studies. However, little is known about its molecular actions and its endogenous targets.

Anti-Müllerian hormone in type 2 and gestational diabetes during the second half of pregnancy: relationship with sexual steroid levels and metabolic parameters.

Hyperandrogenemia and hyperinsulinemia are observed in women with diabetes during pregnancy. The effect of diabetes on anti-Müllerian hormone (AMH) levels during pregnancy is unclear. The aim of this study was to determine the AMH levels in women with type 2 diabetes (T2D) and gestational diabetes (GD) compared to healthy (C) pregnant women during the second half of gestation.

In-vitro study of gonadotrophin signaling pathways in human granulosa cells in relation to progesterone receptor expression.

In humans, data on gonadotrophin-activated (LH, HCG and FSH) progesterone receptor expression and signalling pathways involved in matrix metalloproteinases (MMPs) expression presumably linked to the follicle rupture, are limited. Our hypothesis is LH, HCG and FSH increase progesterone receptor expression in granulosa cells through different signalling pathways, leading to an increased expression of ADAMTS-1 and MMP3/10, which may mediate follicular rupture through the transcription factor, HIF1A. Human granulosa cells were isolated from follicular aspirates obtained from 22 healthy women participating in our IVF programme for male-factor infertility.

The significance of estradiol metabolites in human corpus luteum physiology.

The human corpus luteum (CL) is a temporary endocrine gland derived from the ovulated follicle. Its formation and limited lifespan is critical for steroid hormone production required to support menstrual cyclicity, endometrial receptivity for successful implantation, and the maintenance of early pregnancy. Endocrine and paracrine-autocrine molecular mechanisms associated with progesterone production throughout the luteal phase are critical for the development, maintenance, regression, and rescue by hCG which sustains CL function into early pregnancy.