The relationship between follicle development and progesterone receptor membrane component-1 expression in women undergoing in vitro fertilization

Abstract

Objective To determine the relationship between Progesterone Receptor Membrane Component-1 (PGRMC1) expression and the outcome of in vitro fertilization treatment. Design A prospective study in which PGRMC1 mRNA levels, methylation status of the Pgrmc1 promoter, and the presence of point mutations within Pgrmc1 were obtained from granulosa/luteal cells of women undergoing controlled ovarian hyperstimulation (COH). Setting Fertility center/Basic science laboratory Patients Eighty-five IVF patients and 10 women, who were undergoing COH for the purpose of oocyte donation, were included in this study. Interventions None. Main Outcome Measures PGRMC1 measurements were correlated with clinical outcomes, such as number of follicles, number of retrieved oocytes and ongoing pregnancy rates. Results PGRMC1 mRNA levels within granulosa/luteal cells of 18% of IVF patients were > 2.25 fold higher than those of oocyte donors. Individuals with elevated PGRMC1 mRNA levels had 30% fewer large follicles and fewer oocytes retrieved. The elevated PGRMC1 mRNA levels were associated with an increase in the methylation of Pgrmc1 promoter. Conclusion In patients with elevated PGRMC1 mRNA levels, gonadotropin-induced follicle development is attenuated, although sufficient numbers of follicles develop to allow for embryo transfer and subsequent pregnancy.

PGRMC1 Elevation in Multiple Cancers and Essential Role in Stem Cell Survival

“…PGRMC1 has been previously shown to play a key role in ovarian tumor growth, apoptosis resistance, invasion, angiogenesis, drug resistance and metastasis [5] [21] [42]-[45]. There are also numerous reports linking PGRMC1 to normal ovarian function, including follicle development [46] [47], and is aberrant in premature ovarian failure [48]. Thus, the finding that high PGRMC1-expressing tumors correlate with poor overall survival emphasizes the importance of PGRMC1 as a therapeutic target in ovarian cancer.…”

Array CGH characterization of an unbalanced X-autosome translocation associated with Xq27.2–qter deletion, 11q24.3–qter duplication and Xq22.3–q27.1 duplication in a girl with primary amenorrhea and mental retardation

“…Down-regulation of PGRMC1 has been associated with premature ovarian failure (Mansouri et al, 2008;Schuster et al, 2010) and polycystic ovarian syndrome (Schuster et al, 2010). Overexpression of PGRMC1 has also been associated with impaired follicular development by disrupting the interaction with mitotic spindle apparatus of granulosa cells and inhibiting the mitosis of granulosa cells (Elassar et al, 2012;Lodde and Peluso, 2011). Primary ovarian failure has been noted in females with dup(Xq) involving Xq24 such as dup(X)(q12qter) (Varella-Garcia et al, 1981), dup(X) (q13.3q27.2) (Van Dyke et al, 1983), dup(X)(q22.3q27.3) (Kleczkowska et al, 1993), dup(X) (q22.1q24) (Chen et al, 2011), and t(X;15)(q24;q26.3) involving Xq24 duplication (Giacomozzi et al, 2010).…”

Progesterone Receptor Membrane Component-1 (PGRMC1) and PGRMC-2 Interact to Suppress Entry into the Cell Cycle in Spontaneously Immortalized Rat Granulosa Cells1

“…Similarly, PGRMC1 is expressed at very low levels in women with polycystic ovarian syndrome [5,6]. Finally, poor follicular development is associated with elevated Pgrmc1 mRNA levels in granulosa cells of women undergoing controlled ovarian stimulation as part of their infertility treatment [7]. All three of these clinical examples support a role for PGRMC1 in ovarian follicular development.…”