Further Studies on the Recovery of Fertility in Mice After Protracted Steroid-Induced Sterility

Abstract

Females of strain BALB were maintained sterile for 13 to 20 months by the subcutaneous implantation of pellets containing 40% of 19-nor-progesterone. The life-span of the treated animals was not shorter than that of normal breeding females. Pregnancy can still take place when the pellet is removed after having caused sterility during 395 days, i.e. till the moment when, in normal animals, 98 % of the reproductive task has been fulfilled.The females emerging from a steroid-induced sterility of 395 days behaved as to reproduction like normal aged females: litter frequency and litter size were as small as in the latter.The sterilizing 19-nor-steroid produced ovarian tumours in a considerable percentage of animals. It is not probable that the reproductive activity after removal of the pellets was impaired by these tumours.The experimental conditions as established by the protracted administration of the sterilizing anti-ovulatory steroid represent, supposedly, the maximum sparing of oocytes hitherto obtained. The decline of fertility not being counteracted by this sparing, it would seem that the gerontological decline of fertility is not dependent on the diminished number of oocytes available in the senile ovary.It is not yet possible to locate the gerontological factor responsible for the decline of fertility, in the ovary, or in the hypophysis, or in any other part of the body.Recovery offertility in mice 101

Reproduction in aging normal and neonatally androgenized female rats.

“…The finding that more animals are born in the second or in succeeding litters than in the first litter is present in data by Ingram et al (1958), King (1916), Asdell', Bogart, and Sperling (1941), Biggers. Finn, andMcLaren (1962), andLipschultz, Iglesias, andSalinas (1963).…”

“…It does not appear to be related to the conservation of ova as a result of inhibition of ovulation during pregnancy. This possibility cannot be relevant to the fertility diflerences found between the first and the second pregnancies of young animals Shelton (1959) demonstrated that breeding does not significantly alter the rate of loss of oocytes, and Lipschultz et al (1963) showed that mice prevented from ovulation by implants of 19-nor-progesterone for two thirds of their reproductive life had the same degree of fertility when released from the implants as normally aging animals.…”

Age-Dependent Changes in the Pituitary-- Gonadal Relationship

“…Originally, Lauson, Golden & Sevringhaus (1939) (Hoogstra & Paesi, 1955;Ramirez & McCann, 1963;Barraclough, 1966;Moore, 1965Moore, /1966Matsuyama, Weisz & Lloyd, 1966 (Lipschutz, Igiesias & Salinas, 1963;Verzar, 1966). It appears that in the aged rat pituitary, fsh and lh levels are elevated at a time when ovaries are capable of responding to pmsg (Labhsetwar, 1967a) and the uterus retains the capacity to form deciduomata (Labhsetwar, unpublished observations …”

The Use of Rodents for Studies of Toxicity in Contraceptive Research

“…The chronic administration of progesterone and 19-norprogesterone produce granulosa cell tumours of the ovaries in BALB mice (Lipschutz et al 1963). …”