Apoptosis of human corpora lutea during cyclic luteal regression and early pregnancy

Shikone, Toshihiko

doi:10.1210/jc.81.6.2376

Cited by 62 publications

(37 citation statements)

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“…The apoptotic status of corpora lutea in human ovary is similar to that reported by others (21). In the current study, DNA fragmentation was present in corpora lutea that had positive staining for DNA fragmentation but not in corpora lutea without positive staining for DNA fragmentation.…”

Section: Discussionsupporting

confidence: 92%

Programmed Cell Death in Human Ovary Is a Function of Follicle and Corpus Luteum Status*

Yuan

Giudice

1997

The Journal of Clinical Endocrinology &Amp; Metabolism

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Although extensive investigation on follicular apoptosis (programmed cell death) has been conducted in the infraprimate ovary, there is little information regarding apoptosis and its relationship to follicular status in the human. In this study, apoptosis was investigated in 116 human ovarian follicles (primordial to dominant) and 5 corpora lutea from a total of 27 premenopausal women. Follicles and corpora lutea were evaluated for the presence of DNA fragmentation, characteristic of apoptosis, by two methods: in situ hybridization using 3' end-labeling of DNA with digoxigenin-labeled nucleotides and subsequent digoxigenin antibody and peroxidase staining, and/or biochemical analysis of low molecular weight DNA laddering. Follicle functional status was evaluated by determining follicle sizes and follicular fluid androgen/estrogen (A/E) ratios. No apoptosis was observed in 67 primordial, primary, or secondary follicles. Positive staining for DNA fragmentation was found in a few granulosa cells in 0.1- to 2-mm follicles, whereas abundant staining in granulosa was detected in 2.1- to 9.9-mm follicles. In contrast, no DNA fragmentation was detected in dominant follicles (10-16 mm). The frequency of apoptosis in follicles was calculated to be 37% in 0.1- to 2-mm follicles, 50% in 2.1- to 5-mm follicles, and 27% in 5.1- to 9.9-mm follicles. Abundant low molecular weight DNA laddering was only found in androgen-dominant follicles and not in estrogen-dominant follicles. Positive staining for DNA fragmentation and low molecular weight DNA laddering were observed in degenerating but not healthy-appearing corpora lutea. In the former, DNA fragmentation was found primarily in large luteal cells. These data suggest that follicular atresia in human ovary results from normal programmed cell death and primarily occurs in the granulosa cell layers of the early antral and < 10-mm antral follicles primarily. Furthermore, because apoptosis occurs as early as the 200-mm stage, follicle selection may begin as early as the initial formation of the antrum. The results also suggest that degeneration of the corpus luteum occurs by apoptotic mechanisms.

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Section: Discussionsupporting

confidence: 92%

Programmed Cell Death in Human Ovary Is a Function of Follicle and Corpus Luteum Status*

Yuan

Giudice

1997

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…There was an increase in TNF-α and β mRNA levels in the CL at late luteal phase, when regression is occurring and an increase in apoptotic signals is expected (Shikone et al, 1996;Sugino et al, 2000). Others reported unchanged mRNA levels, but an increase in TNF-α protein, in the bovine CL during the estrous cycle (Petroff et al, 1999;Sakumoto et al, 2000).…”

Section: Discussionmentioning

confidence: 98%

“…There is some evidence that apoptosis occurs during luteolysis (Fraser et al, 1995;Gaytan et al, 1998;Shikone et al, 1996;Sugino et al, 2000;Vaskivuo et al, 2002a;Yuan and Giudice, 1997), but other studies suggest that autophagocytosis is involved in luteal cell death (Fraser et al, 1999;Morales et al, 2000;Quatacker, 1971). Apoptosis can be triggered by multiple different stimuli originating from within or outside the cell.…”

Section: Introductionmentioning

confidence: 99%

Expression and regulation of tumor necrosis factor (TNF) and TNF‐receptor family members in the macaque corpus luteum during the menstrual cycle

Peluffo

Young

Hennebold

et al. 2008

Molecular Reproduction Devel

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Members of the tumor necrosis factor (TNF)-receptor (R) family may be involved in the tissue remodeling that occurs in the primate corpus luteum (CL) during development and regression. As a first step towards addressing this issue, studies assessed TNF ligand-R expression and regulation in CL collected from monkeys during the early (ECL, d3–5), mid (MCL, d7–8), mid-late (MLCL, d10–11), late (LCL, d14–16), and very late (VLCL, menses) luteal phase of the menstrual cycle. CL were also collected after gonadotropin and/or steroid ablation and replacement (with hLH and the progestin R5020) for 3 days at mid-late luteal phase. TNF-α, -β, FAS ligand (FASL), and TNF-R1 mRNA levels were 2- to 6-fold greater (p<0.05) at the MLCL or LCL phase as compared to earlier (ECL, MCL). In contrast, TNF-R2 and FAS mRNA levels did not change during the luteal phase. Immunohistochemical staining for TNF-β, TNF-R1, TNF-R2, FAS, and FASL was observed in luteal cells, whereas only TNF-β staining was observed in endothelial cells. Several TNF-R components were influenced by LH and/or steroid ablation; notably, steroid ablation reduced (p<0.05) luteal TNF-α, but not TNF-β, mRNA levels, which was prevented by progestin treatment. In contrast, steroid ablation increased (p<0.05) luteal cell immunostaining for FAS and FASL, which was reduced by progestin treatment. Thus, several members of the TNF R-ligand family are expressed in the primate CL in an LH- and/or progestin-dependent manner. Peak expression in the late luteal phase may signify a role for the TNF-R system in death receptor-mediated apoptosis during luteolysis.

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“…PGF 2␣ has been shown to inhibit LH-and hCG-induced progesterone production (11,25). Several studies demonstrate that the luteolytic effect of PGF 2␣ is through increasing the production of endothelin-1, which, in turn, inhibits luteal steroidogenesis and induces the release of tumor necrosis factor-␣, a proapoptotic factor (35)(36)(37). In addition, tumor necrosis factor-␣ was found to increase PGF 2␣ production in human granulosa cells (38).…”

Section: Discussionmentioning

confidence: 99%

Role of Mitogen-Activated Protein Kinase in Prostaglandin F_2αAction in Human Granulosa-Luteal Cells¹

Tai

Kang

Choi

et al. 2001

The Journal of Clinical Endocrinology & Metabolism

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In the ovary it has been demonstrated that PGF(2alpha) activates the phospholipase C (PLC)/diacylglycerol/protein kinase C pathway. However, little is known about the downstream signaling events that mediate subsequent cellular responses such as steroidogenesis. The present study was designed to examine the effect of PGF(2alpha) on activation of the mitogen-activated protein kinase (MAPK) signaling pathway and its physiological role in human granulosa-luteal cells (hGLCs). Human GLCs, obtained from women undergoing in vitro fertilization-embryo transfer, were treated with increasing concentrations of PGF(2alpha) (10 nmol/L to 10 micromol/L) for 5 min. For time-course experiments, hGLCs were treated with 1 micromol/L PGF(2alpha) for 1, 5, 10, or 20 min. Western blot analysis, using a monoclonal antibody that detected the phosphorylated forms of extracellular signal-regulated kinases 1 and 2 (p42(mapk) and p44(mapk), respectively), demonstrated that PGF(2alpha) activated MAPK in hGLCs in a dose- and time-dependent manner. Treatment of the cells with neomycin (10 mmol/L; a PLC inhibitor), bisindolylmaleimide I (5 micromol/L; a PKC inhibitor), or PD98059 (50 micromol/L; a MEK inhibitor and a MAPK kinase inhibitor) significantly attenuated the PGF(2alpha)-induced activation of MAPK. In contrast, MAPK activation was not significantly affected by pertussis toxin (200 ng/mL; a G(i) inhibitor) pretreatment. To determine the role of MAPK in steroidogenesis, hGLCs were treated with PGF(2alpha) (1 micromol/L), hCG (1 IU/mL), or PGF(2alpha) plus hCG in the presence or absence of PD98059. Progesterone levels in the culture medium were examined by RIA. Treatment of hGLCs with PGF(2alpha) significantly inhibited hCG-induced progesterone production. The presence of the MEK inhibitor, PD98059, reversed the inhibitory effect of PGF(2alpha) on hCG-induced progesterone production. To our knowledge, it is the first demonstration of PGF(2alpha)-induced activation of the MAPK signaling pathway in the human ovary. These results indicated that PGF(2alpha) activated MAPK subsequent to PLC and PKC activation through pertussis toxin-insensitive G protein in hGLCs. Further, we demonstrated that PGF(2alpha)-induced MAPK activation is associated with modulation of progesterone production. These results support the idea that the MAPK signaling pathway is involved in mediating PGF(2alpha) actions in the human ovary.

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Apoptosis of human corpora lutea during cyclic luteal regression and early pregnancy

Cited by 62 publications

References 0 publications

Programmed Cell Death in Human Ovary Is a Function of Follicle and Corpus Luteum Status*

Programmed Cell Death in Human Ovary Is a Function of Follicle and Corpus Luteum Status*

Expression and regulation of tumor necrosis factor (TNF) and TNF‐receptor family members in the macaque corpus luteum during the menstrual cycle

Role of Mitogen-Activated Protein Kinase in Prostaglandin F_2αAction in Human Granulosa-Luteal Cells¹

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Apoptosis of human corpora lutea during cyclic luteal regression and early pregnancy

Cited by 62 publications

References 0 publications

Programmed Cell Death in Human Ovary Is a Function of Follicle and Corpus Luteum Status*

Programmed Cell Death in Human Ovary Is a Function of Follicle and Corpus Luteum Status*

Expression and regulation of tumor necrosis factor (TNF) and TNF‐receptor family members in the macaque corpus luteum during the menstrual cycle

Role of Mitogen-Activated Protein Kinase in Prostaglandin F2αAction in Human Granulosa-Luteal Cells1

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Role of Mitogen-Activated Protein Kinase in Prostaglandin F_2αAction in Human Granulosa-Luteal Cells¹