The impact of unabated stimulation by human chorionic gonadotropin on the steroid hormone environment of pregnant rats and the spontaneous expression of ovarian cysts in female progeny

Abstract

Unabated stimulation by low doses of human chorionic gonadotropin (hCG) induces ovarian cysts in pregnant rats. In order to determine the impact of these in vivo treatments on the hormonal milieu of pregnancy, and the potential impact of an aberrant cystic-ovary state during pregnancy on the resulting female offspring, pregnant rats were treated with either 0 (control), 1, or 3 IU hCG twice daily for at least 9 days, beginning on day 13 of pregnancy. Serum was harvested from control and hCG treated animals on days 15, 17, 19, and 22 of pregnancy. Control pregnant rats and animals treated with 1 IU hCG shared similar serum profiles for progesterone (P4), androstenedione (A4), 5alpha-androstane-3alpha,17beta-diol (3alpha-diol), androsterone (A5), and estrone (E1) between days 15 and 22 of pregnancy. Testosterone serum concentrations were similar for control and 1 IU hGG-treated pregnant rats between days 15 and 19 of pregnancy; whereas, on day 22, 1 IU hGG-treated pregnant rats displayed lower serum testosterone than control pregnant rats (P < or = 0.05). In contrast, serum estradiol (E2) concentrations for 1 IU hCG- treated pregnant rats were greater than E2 values observed for control rats on days 15-19 of pregnancy (P < or = 0.05). Serum testosterone and 3alpha-diol values for 3 IU hCG-treated pregnant rats differed from those of control pregnant rats only on day 19 when these values were transiently greater for these hCG-treated animals compared with serum values for control pregnant rats (P < or = 0.05). Serum A4 values for 3 IU hCG-treated pregnant rats were elevated compared to values for control pregnant rats only on days 15 and 17 (P < or = 0.05). In contrast, serum E1, A5, and E2 were elevated on days 19-22, 17-22, and 15-22, respectively, in 3 IU hCG-treated pregnant rats compared to control pregnant rats (P < or = 0.05). No pups from control pregnant rats displayed ovarian cysts during the time they were observed postnatally. In contrast, 6 of 25 pups from 3 IU hCG-treated pregnant rats displayed cystic ovaries, without corpora lutea, on day 55 of age. Serum steroid concentrations for these cyst-bearing progeny were similar to those of female progeny from control pregnant rats, whereas female progeny without ovarian cysts from 3 IU hCG-treated pregnant rats displayed differences in serum steroid values from those of progeny from control pregnant rats (P < or = 0.05). The data support the concept that an aberrant, yet physiologic hormonal environment associated with the induction of ovarian cysts during pregnancy in rats, can lead to the spontaneous establishment of an ovarian cystic state in at least a subset of the female progeny. Further, the date suggest that tonically increased ovarian estrogen production during pregnancy, reflected by tonically elevated peripheral serum estrogen concentrations, may play a pivotal role in the etiology of an ovarian cystic state in this subset of daughters from hCG-induced, cyst-bearing pregnant rats.