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Follicular Atresia as an Apoptotic Process: Atresia-Associated Increase in the Ovarian Expression of the Putative Apoptotic Marker Sulfated Glycoprotein-2

  • Reproductive Endocrinology
  • Published:
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Abstract

Objective

TO evaluate the possibility that morphologically confirmed/hypophysectomy-induced ovarian follicular atresia, a putative apoptotic process, is coupled to alterations in the steady-state levels of ovarian sulfated glycoprotein-2 (SGP-2) transcripts.

Methods

Hypophysectomy-induced follicular atresia in immature rats, morphologically confirmed at the light and electron microscopic levels, was correlated with alterations in the steady-state levels of ovarian SGP-2 transcripts as assessed by a solution hybridization/RNase protection assay. Cellular localization was accomplished by in situ hybridization technology.

Results

Hypophysectomy of the 24-day-old immature rat, an established precipitant of follicular atresia, led (3 days later) to a significant (V <.05) increase (up to 3.3-fold) in the relative abundance of densitometrically quantified ovarian SGP-2 transcripts compared with age-matched intact controls. Detailed time-course analysis after hypophysectomy revealed significantly (V <.05) increased ovarian SGP-2 mRNA expression as early as 2 days after hypophysectomy; no further increments were noted on days 4 or 8. Light microscopic analysis of comparable ovarian material 4 days after hypophysectomy revealed increased numbers of atretic follicles displaying large numbers of degenerating granulosa cells. Electron microscopic analysis of the degenerating cells of atretic follicles (from hypophysectomized rats) disclosed nuclear condensation and cytoplasmic shrinkage as well as apoptotic bodies at all levels of the granulosa cell layer. In situ hybridization established the granulosa cell of the intact untreated rat as the somatic cell concerned with SGP-2 gene expression. In turn, hypophysectomy led to an increase in SGP-2 expression at the level of the theca-interstitial cell, an effect prevented by the concurrent provision of pregnant mare serum gonadotropin (PMSG). The hypophysectomy-induced increase in ovarian SGP-2 transcripts was similarly reversed (54% inhibition by day 21) by the concomitant provision of FSH, an established antiatretic principle. The delayed administration (day 26) of a single dose of PMSG to rats hypophysectomized on day 24 eliminated the hypophysectomy-induced increase in ovarian SGP-2 transcripts as assessed on day 28. Qualitatively similar but quantitatively more pronounced increments in ovarian SGP-2 gene expression were obtained when atresia was induced by hypophysectomy of PMSG-primed immature rats.

Conclusions

These observations establish the immature rat ovary as a site of SGP-2 gene expression and reveal hypophysectomy-induced follicular atresia to result in the up-regulation of ovarian (specifically, thcca-interstitial) SGP-2 gene expression, an effect prevented by the concurrent provision of FSH or PMSG. To the extent that SGP-2 is an acceptable apoptotic marker, the present findings support the hypothesis that ovarian follicular atresia may be an apoptotic process. (J Soc Gynecol Invest 1996;3:199-208)

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Author information

Authors and Affiliations

  1. Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, and the Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, 21201, USA, 405 W. Redwood Street. Third Floor

    Arye Hurwitz MD, Kristiina Ruutiainen-Altman PhD, MD, Louis Marzella PhD, Luis Botero MD, Matat Dushnik MD &  Eli Y. Adashi MD

  2. Department of Obstetrics and Gynecology, Hadassah University Hospital., Mount Scopus, Jerusalem, Israel

    Matat Dushnik MD

  3. Departamento de Gineco-Obstetncia (3rd PISO), Unniersidad Javeriana. Hospital San Ignacio., Bogota, Colombia

    Luis Botero MD

Authors
  1. Arye Hurwitz MD
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  2. Kristiina Ruutiainen-Altman PhD, MD
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  3. Louis Marzella PhD
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  5. Matat Dushnik MD
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Additional information

Supported in part bv research grants HD-19998 and HD-30288 from the National Institute for Health and Human Development. National Institutes of Health (EYA).

Arye Hurwitz is the recipient of a Serono Fellowship and an American Physician Award.

Kristiina Ruutiainen-Altman is the recipient of a Fogarty International Fellowship Award, a Lalor Foundation Award, a Finnish Culture Foundation Award, and an award from the Academy of Finland.

Luis Botero is the recipient of a Rockefeller Fellowship Award.

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Hurwitz, A., Ruutiainen-Altman, K., Marzella, L. et al. Follicular Atresia as an Apoptotic Process: Atresia-Associated Increase in the Ovarian Expression of the Putative Apoptotic Marker Sulfated Glycoprotein-2. Reprod. Sci. 3, 199–208 (1996). https://doi.org/10.1177/107155769600300407

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