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1 March 2004 Localization and Developmental Expression of the Activin Signal Transduction Proteins Smads 2, 3, and 4 in the Baboon Fetal Ovary
Reinhart B. Billiar, J. Benjamin St. Clair, Nicholas C. Zachos, Marcia G. Burch, Eugene D. Albrecht, Gerald J. Pepe
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Abstract

We recently demonstrated that the reduction in the number of primordial follicles in ovaries of near-term baboon fetuses deprived of estrogen in utero was associated with increased expression of α-inhibin, but not activin βA and βB or the activin receptors. Therefore, we proposed that estrogen regulates fetal ovarian follicular development by controlling the intraovarian inhibin:activin ratio. As a prelude to conducting experiments to test this hypothesis, in the current study we determined whether the primate fetal ovary expressed Smads 2/3 and 4 and whether expression of these activin-signaling proteins was altered in fetal ovaries of baboons in which estrogen production was suppressed. Western blot analyses demonstrated that the 59 kDa Smad 2, 54 kDa Smad 3, and 64 kDa Smad 4 proteins were expressed in fetal ovaries of untreated baboons at both mid and late gestation and that the level of expression was not significantly altered in late gestation by in vivo treatment with CGS 20267 or CGS 20267 and estrogen. Immunocytochemistry localized Smads 2/3 and 4 to cytoplasm of oocytes and pregranulosa cells at midgestation and oocytes and granulosa cells of primordial follicles in late gestation. Smad 4 was also detected in granulosa cell nuclei in late gestation, and nuclear expression appeared to be decreased in fetal ovaries of baboons deprived of estrogen. The site of localization of Smads correlated with localization of the activin receptors IA and IIB, which we previously showed were abundantly expressed in oocytes and (pre)granulosa cells at both mid and late gestation and unaltered by estrogen deprivation. In summary, the results of the current study are the first to show that the intracellular signaling molecules required to transduce an activin signal are expressed in the baboon fetal ovary and that expression was not altered by estrogen deprivation in utero. These findings, coupled with our previous observations showing that estrogen deprivation reduced follicle numbers and upregulated/induced expression of inhibin but not activin or the activin receptors, lend further support to the hypothesis that estrogen regulates fetal ovarian folliculogenesis by controlling the intraovarian activin:inhibin ratio.

Reinhart B. Billiar, J. Benjamin St. Clair, Nicholas C. Zachos, Marcia G. Burch, Eugene D. Albrecht, and Gerald J. Pepe "Localization and Developmental Expression of the Activin Signal Transduction Proteins Smads 2, 3, and 4 in the Baboon Fetal Ovary," Biology of Reproduction 70(3), 586-592, (1 March 2004). https://doi.org/10.1095/biolreprod.103.018598
Received: 22 April 2003; Accepted: 1 October 2003; Published: 1 March 2004
KEYWORDS
activin
estradiol
follicular development
ovary
pregnancy
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