Department of Obstetrics and Gynecology, Yamaguchi University
School of Medicine (N.S., S.K., A.K., S.T., H.K.), Minamikogushi 1-1-1,
Ube 755-8505, Japan; and Department of Pathology, Tohoku University
School of Medicine (T.S.), 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575,
Japan
Address all correspondence and requests for reprints to: Norihiro Sugino, M.D., Department of Obstetrics and Gynecology, Yamaguchi University School of Medicine, Minamikogushi 1-1-1, Ube 755-8505, Japan. E-mail: obgyn{at}po.cc.yamaguchi-u.ac.jp
To investigate the relationship between apoptosis and the Bcl-2/Bax
systemin the human corpus luteum (CL), the frequency of apoptosisand
expression of Bcl-2 and Bax were examined in the CL duringthe
menstrual cycle and in early pregnancy. In situ analysis
ofDNA fragmentation showed that the number of apoptotic cellswas much
greater in the regressing CL than that in the midlutealphase CL,
whereas there were almost no apoptotic cells in theCL of early
pregnancy. Immunohistochemistry revealed that Bcl-2expression was
observed in the luteal cells in the midlutealphase and early
pregnancy, but not in the regressing CL. Incontrast, Bax
immunostaining was observed in the regressingCL, but not in the
midluteal phase and early pregnancy. bcl-2messenger
ribonucleic acid (mRNA) levels in the CL during themenstrual cycle
were highest in the midluteal phase and lowestin the regressing CL. In
the CL of early pregnancy, bcl-2 mRNAlevels were
significantly higher than those in the midlutealphase. In contrast,
bax mRNA levels were highest in the regressingCL and
remarkably low in the CL of early pregnancy. Westernblot analyses
revealed that Bcl-2 expression was significantlylower in the
regressing CL than in the midluteal phase and earlypregnancy, and that
Bax expression was, in contrast, significantlyhigher in the regressing
CL than in the midluteal phase andwas remarkably low in the CL of
early pregnancy. When corporalutea of the midluteal phase were
incubated with hCG, hCG significantlyincreased the mRNA and protein
levels of Bcl-2 and significantlydecreased those of Bax. In
conclusion, Bcl-2 and Bax may playimportant roles in the regulation of
the life span of the humanCL by controlling the rate of apoptosis. hCG
may act to prolongthe life span of the CL by increasing Bcl-2
expression and decreasingBax expression when pregnancy occurs.
This article has been cited by other articles:
A. Bowolaksono, R. Nishimura, T. Hojo, R. Sakumoto, T. J. Acosta, and K. Okuda Anti-Apoptotic Roles of Prostaglandin E2 and F2alpha in Bovine Luteal Steroidogenic Cells
Biol Reprod,
August 1, 2008;
79(2):
310 - 317.
[Abstract][Full Text][PDF]
R. Nishimura, J. Komiyama, Y. Tasaki, T. J. Acosta, and K. Okuda Hypoxia Promotes Luteal Cell Death in Bovine Corpus Luteum
Biol Reprod,
March 1, 2008;
78(3):
529 - 536.
[Abstract][Full Text][PDF]
F. Del Canto, W. Sierralta, P. Kohen, A. Munoz, J. F. Strauss III, and L. Devoto Features of Natural and Gonadotropin-Releasing Hormone Antagonist-Induced Corpus Luteum Regression and Effects of in Vivo Human Chorionic Gonadotropin
J. Clin. Endocrinol. Metab.,
November 1, 2007;
92(11):
4436 - 4443.
[Abstract][Full Text][PDF]
A. Rolaki, G. Coukos, D. Loutradis, H. M. DeLisser, C. Coutifaris, and A. Makrigiannakis Luteogenic Hormones Act through a Vascular Endothelial Growth Factor-Dependent Mechanism to Up-Regulate {alpha}5{beta}1 and {alpha}v{beta}3 Integrins, Promoting the Migration and Survival of Human Luteinized Granulosa Cells
Am. J. Pathol.,
May 1, 2007;
170(5):
1561 - 1572.
[Abstract][Full Text][PDF]
S. Berndt, S. P. d'Hauterive, S. Blacher, C. Pequeux, S. Lorquet, C. Munaut, M. Applanat, M. A. Herve, N. Lamande, P. Corvol, et al. Angiogenic activity of human chorionic gonadotropin through LH receptor activation on endothelial and epithelial cells of the endometrium
FASEB J,
December 1, 2006;
20(14):
2630 - 2632.
[Abstract][Full Text][PDF]
E. C. Chao and S. M. Lipkin Molecular models for the tissue specificity of DNA mismatch repair-deficient carcinogenesis
Nucleic Acids Res.,
February 6, 2006;
34(3):
840 - 852.
[Abstract][Full Text][PDF]
K. A Slot, M. Voorendt, M. de Boer-Brouwer, H. H van Vugt, and K. J Teerds Estrous cycle dependent changes in expression and distribution of Fas, Fas ligand, Bcl-2, Bax, and pro- and active caspase-3 in the rat ovary
J. Endocrinol.,
February 1, 2006;
188(2):
179 - 192.
[Abstract][Full Text][PDF]
A. Matsuoka-Sakata, H. Tamura, H. Asada, I. Miwa, T. Taketani, Y. Yamagata, and N. Sugino Changes in vascular leakage and expression of angiopoietins in the corpus luteum during pregnancy in rats
Reproduction,
February 1, 2006;
131(2):
351 - 360.
[Abstract][Full Text][PDF]
N. Sugino, T. Suzuki, A. Sakata, I. Miwa, H. Asada, T. Taketani, Y. Yamagata, and H. Tamura Angiogenesis in the Human Corpus Luteum: Changes in Expression of Angiopoietins in the Corpus Luteum throughout the Menstrual Cycle and in Early Pregnancy
J. Clin. Endocrinol. Metab.,
November 1, 2005;
90(11):
6141 - 6148.
[Abstract][Full Text][PDF]
M. R. Hussein Apoptosis in the ovary: molecular mechanisms
Hum. Reprod. Update,
March 1, 2005;
11(2):
162 - 178.
[Abstract][Full Text][PDF]
Y. Kumazawa, K. Kawamura, T. Sato, N. Sato, Y. Konishi, Y. Shimizu, J. Fukuda, H. Kodoma, and T. Tanaka HCG up-regulates survivin mRNA in human granulosa cells
Mol. Hum. Reprod.,
March 1, 2005;
11(3):
161 - 166.
[Abstract][Full Text][PDF]
K. Okuda, A. Korzekwa, M. Shibaya, S. Murakami, R. Nishimura, M. Tsubouchi, I. Woclawek-Potocka, and D. J. Skarzynski Progesterone Is a Suppressor of Apoptosis in Bovine Luteal Cells
Biol Reprod,
December 1, 2004;
71(6):
2065 - 2071.
[Abstract][Full Text][PDF]
V. K. Yadav, P. Muraly, and R. Medhamurthy Identification of novel genes regulated by LH in the primate corpus luteum: insight into their regulation during the late luteal phase
Mol. Hum. Reprod.,
September 1, 2004;
10(9):
629 - 639.
[Abstract][Full Text][PDF]
S. Takiguchi, N. Sugino, K. Esato, A. Karube-Harada, A. Sakata, Y. Nakamura, H. Ishikawa, and H. Kato Differential Regulation of Apoptosis in the Corpus Luteum of Pregnancy and Newly Formed Corpus Luteum after Parturition in Rats
Biol Reprod,
February 1, 2004;
70(2):
313 - 318.
[Abstract][Full Text][PDF]