The Progesterone Receptor Knockout Mouse Model

Abstract

During the first decade of the twentieth centry, a series of classic experiments performed by the noted European embryologists Fraenkel, Loeb, Bouin, and Ancel unequivocally demonstrated the essential role of the corpus luteum in the establishment and maintenance of pregnancy (reviewed in 1,2). Subsequent investigations in the 1920s revealed that organic extracts of the corpus luteum were able to elicit the distinctive histological and physiological phenotype of the endometrium (termed “progestational proliferation”), characteristic of early pregnancy in ovariectomized (OVX) rabbits (reviewed in 3). If the animals were mated 1 d prior to ovariectomy, chronic administration of these extracts was sufficient to maintain normal development of the embryo to term. In the early 1930s, the “internal secretion” of the corpus luteum, responsible for these utero-morphic changes was identified and purified by Willard M. Allen at the University of Rochester, NY, which he names “progestrin,” a substance that favors gestation (4). The discovery of progestin, or progesterone, heralded a new era in reproductive medicine, and it was initially envisioned that the hormone would be used to reduce or inhibit such female fertility disorders as spontaneous miscarriages in women at high risk (reviewed in 5). Ironically, during the following decades, the use of progesterone (in derivative form) as a female contraceptive agent (“the pill”) would overshadow its original promise as a fertility drug (6,7).