Pregnancy in young and aged rats. I. Ovarian progesterone and 20 alpha-hydroxypregn-4-en-3-one formation.

Abstract

The conversions of [3H]pregnenolone (P5) to [3H]progesterone (P4) and [3H]20 alpha-hydroxypregn-4-en-3-one (20-OHP4) were determined in vitro in ovaries of 3 (young)- and 11 (aged)-month-old rats throughout pregnancy. Aged females exhibited an increased incidence of embryonic-fetal resorption beginning at midgestation. The mean +/- SE numbers of live and dead fetuses in aged females between day 11 of gestation and term were 8.6 +/- 0.5 and 2.3 +/- 0.3, respectively, compared to 12.0 live fetuses in young females. In young animals, ovarian conversion of P5 to P4 approximated 30% on days 1-3 of gestation, increased (P less than 0.001) to a plateau of about 45% on days 6-11, then declined to 23.5% by day 15. In aged females, ovarian formation of P4 from P5 showed no significant progressive rise or fall throughout pregnancy. The increment in P4 formation observed on days 6-11 in young rats, therefore, did not occur in aged females, and the percent conversion of P5 to P4 was 40% lower (P less than 0.05 to P less than 0.005) in aged rats during this interval. Ovarian P4 formation was similarly low in aged females that did or did not exhibit embryonic death on days 9-11. From day 12 of gestation until term, the percent conversion of P5 to P4 was similar in all young and aged animals. Conversion of P5 to 20-OHP4 in young rats increased (P less than 0.005) steadily to a peak of 21.9 +/- 5.8% (mean +/- SE) at midgestation, then declined thereafter. 20-OHP4 formation was about 50% greater in aged than in young females on days 2-6, but values were similar thereafter. The mean ratio of conversion of P5 to P4 to that of P5 to 20-OHP4, therefore, was 50% lower (P less than 0.025) in aged (1.8 +/- 0.2) than in young (3.3 +/- 0.4) rats between days 6 and 11 of gestation. The subnormal amount of P4 recovered after ovarian incubation in aged females apparently reflected subnormal P4 formation and/or enhanced P4 catabolism to steroid metabolites. The present results, therefore, demonstrate intrinsic changes in ovarian function during aged rat pregnancy. The onset of fetal demise in aged females, however, does not appear to be related to this alteration in ovarian steroidogenesis.