Contribution of the Ovary Versus Hypothalamus-Pituitary to Termination of Estrous Cycles in Aging Rats Using Ovarian Transplants

BIOLOGY OF REPRODUCTION Contribution 27, 29-37 (1982) of the Ovary Versus Hypothalamus-Pituitary Termination of Estrous Cycles in Aging Rats Using Ovarian Transplants1 VICTORIA M. SOPELAK2 and Department of Obstetrics West Virginia University West L. BUTCHER3 and Gynecology Medical Center Virginia 26506 Morgantown, ROY to ABSTRACT Vaginal between pituitary smear young in the patterns were and old termination rats monitored to of for 80 days after examine the estrous cyclic importance activity. At orthotopic of the ovarian transplants (OvTr) the ovary and the hypothalamusend of this period, the rats were sacrificed at 2200 and ovaries were h, blood was collected for measurement of ovarian steroids and gonadotropins, prepared for histological study. A second experiment examined the effect of a reduction in ovarian tissue by unilateral ovariectomy of old rats on estrous cyclicity during the first 16 days following surgery. During the 80 days of observation, 25% of the old and 0% of the young sham-operated rats showed irregular estrous cycles. This decrease in cyclicity followed a decrease in the total number of oocytes in the ovaries. Rats with OvTr did not cycle as regularly as young or old intact rats; and 75% of both young and old recipients with OvTr were acydic by Day 80. Ovarian factors were implicated in the termination of cyclicity since: 1) old ovaries in either old or young recipients were found to have a limited ability to maintain cyclicity compared to young or prepuberal ovaries; 2) rats with OvTr which continued to cycle had more ovarian tissue and oocytes than rats which had become constantly estrous or anestrous, but fewer oocytes than intact rats; and 3) in Experiment 2, a greater number of old unilaterally ovariectomized rats demonstrated irregular cycles by 16 days after surgery compared to old intact rats. Within the group of acyclic rats with OvTr, more (P<0.05) old than young recipients became constantly estrous, while more young than old recipients became anestrous. Since numbers of follicles were not different between rats with constant estrus and anestrus, this suggested that there also were alterations at the hypothalamicpituitary axis with advancing age. As long as cyclicity was maintained, there were no significant differences in serum concentrations of the 6 measured steroids or prolactin at 2200 h on metestrus between luteinizing rats with rats with OvTr. However, compared to intact rats, concentrations of and follicle-stimulating hormone (FSH) were increased in the cycling increase in Lii and FSH occurred during constant estrus, with castration found in anestrous rats. The increase in gonadotropins and the decrease in estrous cyclic accompanied a decrease in the number of growing follicles. This increase in gonadotropins levels activity intact rats and hormone (LH) OvTr. A further cannot be explained by changes in steroids alone, since a significant decline in ovarian steroids was not found at this particular sampling time, except in rats with OvTr which were anestrous. It is concluded that a reduced amount of ovarian tissue and number of follicles plays a major role in the some decline difference constant estrus in at the in older reproductive function, probably hypothalamic-pituitary axis through a reduction is responsible for in inhibin. the increased However, incidence of rats. INTRODUCTION Accepted February Received August ‘This investigation search Grant AG-02 Aging. 2Present address: National velopment, 12, 1982. 18, 1981. was supported 311 from the National Aged by NIH Institute Reof irregular and Research Branch, Institute of Child Health and Human DeNational Institutes of Health, Bethesda, MD Roy L. Butcher, West Virginia WV 26506. Dept. University show cycles (Ingram, 1959) and a decline Shelton, an increased incidence for of this (Adams, Studies 29 age-related 1970; of Finch, the decline in The hypohave each responsible reproduction 1978;Talbert, initial changes of 1959; Mandl in fertility with advancing age (Talbert, 1968). thalamus, pituitary, ovary and uterus been implicated as the primary site Pregnancy 20205. 3Reprint requests: Dr. Obstetrics and Gynecology, Medical Center, Morgantown, rats estrous 1978). in the hypo- SOPELAK 30 thalamus, pituitary ciated with often utilized the ovary decrease animals reproductive acyclic times and the which in in the senescence assohave are fecundity, terminal or stages end results rather to than of ovariectomized rats which are steroid primed, and included rats with pituitary tumors. contributing AND the someThus, initiating reproductive factors aging, been age of the studied. Krohn ovary (1962) played suggested a major that role the in maintenance estrous ovaries cycles, since transplants into acyclic old CBA estrous planted cycles, into cycles or transplanted (1965) the Peng and gate ovaries transin irregular Using young ovaries old rats, Aschheim Huang (1972) hypothalamus-pituitary mary site of aging of cyclic activity. The present the effects young restored mice acyclic old mice resulted failure to cycle. into acyclic and that while young of of led to the study was undertaken of the age of the the pri- termination ovary to investiand the age of the recipient topic transplants of on cyclic prepuberal, ovaries age of to study the effects of the the decline in regularity of were utilized the ovary on estrous used trols cycles. young as ovarian transplant to elucidate changes which onset of sacrifice, analysis evaluation gain old rats recipients and hypothalamic-pituitary have occurred estrous understanding aging. ovariectomies to study and Orthoand old cycles. were as con- prior At the to the time of blood was collected for hormonal and ovaries were saved for histological of the oocyte population in order an eral may irregular reproductive sue Cycling activity. young the on estrous of Control were effect cyclic MATERIALS the of to mechanism surgery performed on a decrease of or unilatold in ovarian rats tis- activity. AND METHODS Estrous cycles of sexually mature rats were monitored by daily vaginal smears and only those rats exhibiting at least 3 consecutive 4- or 5-day cycles were utilized in this study. Old rats with tumors, irregular cycles or unthrifty appearance were discarded. Ovarian Transplantation the first experiment, ovarian transplants (OvTr) young age age) and on the and old rats recipient termination age of reproductive cyclicity. Sham-operated young and old rats served as controls for age effects, whereas young rats with young OvTr and old rats with old OvTr served as controls for the effects of transplantation. The 8 treatments (N = 15-17 rats/group) included the following: 1) young sham-operated controls; 2 (...truncated)