From: Doug Skrecky (oberon@vcn.bc.ca)
Date: Thu Oct 14 1999 - 23:17:16 MDT
Authors
Perez GI. Robles R. Knudson CM. Flaws JA. Korsmeyer SJ. Tilly JL.
Institution
Vincent Center for Reproductive Biology, Massachusetts General Hospital and
Department of Obstetrics, Gynecology and Reproductive Biology, Harvard
Medical School, Boston 02114, USA.
Title
Prolongation of ovarian
lifespan into advanced chronological age by Bax-deficiency.
Source
Nature Genetics. 21(2):200-3, 1999 Feb.
Abstract
Female mammals are endowed with a finite number of oocytes at birth, each
enclosed by a single layer of somatic (granulosa) cells in a primordial
follicle. The fate of most follicles is atretic degeneration, a process that
culminates in near exhaustion of the oocyte reserve at approximately the
fifth decade of life in women, leading to menopause. Apoptosis has a
fundamental role in follicular atresia, and recent studies have shown that
Bax, which is expressed in both granulosa cells and oocytes, may be central
to ovarian cell death. Here we show that young adult female
Bax-/- mice possess threefold more primordial follicles in their
ovarian reserve than their wild-type sisters, and this
surfeit of follicles is maintained in advanced chronological age, such that
20-22-month-old female Bax-/- mice possess hundreds of follicles at all
developmental stages and exhibit ovarian steroid-driven
uterine hypertrophy. These observations contrast with the
ovarian and uterine atrophy seen in aged wild-type female
mice. Aged female Bax-/- mice fail to become pregnant when housed with young
adult males; however, metaphase II oocytes can be retrieved from, and corpora
lutea form in, ovaries of aged Bax-/- females following superovulation with
exogenous gonadotropins, and some oocytes are competent for in vitro
fertilization and early embryogenesis. Therefore, ovarian
lifespan can be extended by selectively disrupting Bax
function, but other aspects of normal reproductive performance remain
defective in aged Bax-/- female mice.
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