Mutant mouse models and their contribution to our knowledge of corpus luteum development, function and regression

Abstract

The corpus luteum is a unique organ, which is transitory in nature. The development, maintenance and regression of the corpus luteum are regulated by endocrine, paracrine and autocrine signaling events. Defining the specific mediators of luteal development, maintenance and regression has been difficult and often perplexing due to the complexity that stems from the variety of cell types that make up the luteal tissue. Moreover, some regulators may serve dual functions as a luteotropic and luteolytic agent depending on the temporal and spatial environment in which they are expressed. As a result, some confusion is present in the interpretation of in vitro and in vivo studies. More recently investigators have utilized mutant mouse models to define the functional significance of specific gene products. The goal of this mini-review is to identify and discuss mutant mouse models that have luteal anomalies, which may provide some clues as to the significance of specific regulators of corpus luteum function.

Gq/11-Dependent Changes in the Murine Ovarian Transcriptome at the End of Gestation1

“…As pregnancy progresses, expression of the luteal PGF2α receptor increases [ 21 – 24 ], and it is engaged by uterine-derived PGF2α [ 25 ], which, through the activation of G q/11 [ 4 ], increases the expression of the Ark1c18 gene and the conversion of progesterone to 20α-hydroxyprogesterone [ 26 – 29 ]. The resulting drop in progesterone ultimately allows uterine contractions and parturition to begin (reviewed in Davis and Rueda [ 25 ], Ratajczak and Muglia [ 39 ], Stocco et al [ 40 ], and Henkes et al [ 41 ]). We cannot assume, however, that all actions of PGF2α are mediated by G q/11 , because the PGF2α receptor also activates G 12/13 [ 5 ].…”

“…The decrease in Lhcgr reduces the responsiveness of luteal cells to hCG, the decrease in Inha results in a reduction in the circulating levels of Inhibin A, and the decrease in the three steroidogenic enzymes is associated with a decrease in circulating estradiol levels. We hypothesize that the G α q/11 -dependent decrease in expression of Lhcgr , Cyp17a1 , Cyp19a1 , and Hsd17b7 , and the increase in expression of Akr1c18 coordinate the drop in circulating progesterone and estradiol that occurs at the end of gestation [ 4 , 25 – 29 , 39 – 41 ]. The decrease in Lhcgr reduces the stimulus for progesterone synthesis, and the increase in Akr1c18 enhances progesterone metabolism.…”

“…The failure of parturition and lack of progesterone withdrawal observed in the Ptgfr null mice shows that activation of the luteal PGF2α receptor is the trigger for parturition in mice (reviewed in Davis and Rueda [ 25 ], Ratajczak and Muglia [ 39 ], Stocco et al [ 40 ], and Henkes et al [ 41 ]). Because we have recently shown that the phenotype of G α q f/f ;G α 11 −/− ;Cre + mice is very similar to that of the Ptgfr null mice, and because luteal cells derived from G α q f/f ;G α 11 −/− ;Cre + mice fail to respond to PGF2α with an increase in Akr1c18 expression, we concluded that the effects of the luteal PGF2α receptor on the induction of Akr1c18 are mediated by the activation of G q/11 [ 4 ].…”

Effects of Endocrine-disrupting Chemicals on Female Reproductive Health

“…Following ovulation, the remnants of the ovulated follicle are stimulated by LH to terminally differentiate into the corpus luteum (CL). The CL, as a primary source of progesterone, is essential for enabling the initiation and maintenance of pregnancy (reviewed in [71,72]). …”