Reproductive senescence in female C57BL/6J mice: Ovarian impairments and neuroendocrine impairments that are partially reversible and delayable by ovariectomy

C. V. Mobbs, D. M. Gee, C. E. Finch

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63 Scopus citations

Abstract

Ovarian and neuroendocrine impairments were examined before and after the age-correlated loss of estrous cycles in C57BL/6J female mice. The role of ovarian secretions in inducing neuroendocrine impairments before and after the loss of estrous cycles was also examined by determining neu-roendocrine impairments after prolonged ovariectomy. Young (6-month-old) cycling, middle-aged (12-, 14-, and 16-month-old) cycling or acyclic, and old (18-month-old) acyclic mice were used. Ovarian impairments were assessed by grafting old ovaries into young hosts. Neuroendocrine impairments were assessed by grafting young ovaries into middle-aged and old hosts, ovariec-tomized either at grafting or 2 months before, and by inducing a LH surge in mice that had been ovariectomized for 4 days, 1 month, or 2 months. One group of 16-month-old and one group of 18-month-old mice were also ovariectomized at 6 months of age; these groups were used to examine the steroid-induced LH surge. The LH surge was induced by inserting sc a single priming estradiol (E2) implant, followed by two more (surge-inducing) implants 6 days later; 33 h after the second implantation, mice were decapitated (1800 h). The number of estrous cycles supported by middle-aged and old ovaries grafted into young hosts was reduced by more than 90% compared with that in young ovaries. The number of estrous cycles supported by middle-aged and old hosts given young ovarian grafts was reduced by 60% and 90%, respectively, compared with that in young hosts. Middle-aged and old hosts also had progressively longer estrous cycles than young hosts. Levels of the E2-induced LH surge in middle-aged and old mice were also reduced by 60% and 90%, respectively, compared with levels in young mice. In old acyclic mice, ovariectomy for 2 months partially reversed impairments in the LH surge and partially restored the ability to support cycles with young grafts; these functions, normally 90% impaired in old mice, were only 60% impaired after prolonged ovariectomy. Moreover, ovariectomy 2 months before grafting in old hosts resulted in snorter estrous cycles and 60% fewer pituitary adenomas. In middle-aged cycling mice, ovariectomy for 2 months did not affect impairments in the LH surge or in the ability to support estrous cycles with young grafts; these functions remained 60% impaired in middle-aged mice ovariectomized for 2 months. If mice were ovariectomized when young, the age-correlated impairments of the E2-induced LH surge at 16 months were largely prevented. We conclude that both ovarian and neuroendocrine impairments occur during reproductive senescence in female mice before and after estrous cycles cease. Exposure to ovarian secretions during estrous cycles causes neuroendocrine impairments by middle age; these middle-age impairments are not reversed by ovariectomy for 2 months, but can be prevented by ovariec-tomy when young. After estrous cycles cease, further exposure to secretions from polyfollicular acyclic ovaries causes additional neuroendocrine impairments; these additional impairments can be reversed by prolonged ovariectomy.

Original languageEnglish
Pages (from-to)1653-1662
Number of pages10
JournalEndocrinology
Volume115
Issue number5
DOIs
StatePublished - 1984
Externally publishedYes

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