Apoptosis in the human uterine endometrium during the menstrual cycle.

Kokawa, Katsuji; Shikone, Toshihiko; Nakano, Ryuichi

doi:10.1210/jcem.81.11.8923873

Cited by 74 publications

(46 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings suggest that autophagy occurs primarily in the glandular cells of the secretory endometrium during the menstrual cycle. This pattern is similar to the previous observation that apoptosis was detected in the glandular epithelium of the late secretory phase and menstruating endometrium, whereas very little apoptosis was detected during the proliferative phase or at the beginning of the secretory phase [3][4][5]. Therefore, endometrial cell autophagy may be involved in the regulation of the human endometrial cycle.…”

Section: Discussionsupporting

confidence: 90%

“…These sequential changes are generally regarded as being associated with ischemic necrosis of the functional layer of the endometrium caused by contraction of the spiral arteries, with the process being dependent on the concentration of sex hormones [1,2]. In contrast to earlier findings, recent studies have detected apoptosis, a form of programmed cell death (PCD), in the endometrial epithelial cells during the late secretory phase and in the menstruating endometrium, whereas very little apoptosis has been detected during the proliferative phase or at the beginning of the secretory phase [3][4][5]. Therefore, apoptosis appears to be the common pathway of cell death for eliminating senescent endometrial cells from the functional layer of the human endometrium during the late secretory and menstrual phases of the cycle [6,7].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Role of Autophagy in Human Endometrium1

Choi

Lee

et al. 2012

Biology of Reproduction

View full text Add to dashboard Cite

Autophagy appears to play an important role in the normal development and maintenance of homeostasis in a variety of tissues, including the female reproductive tract. However, the role of autophagy and the association between autophagy and apoptosis in cyclic remodeling of the human endometrium have not been described. Therefore, we investigated the involvement of autophagy during the human endometrial cycle and its association with apoptosis. Endometrial samples were obtained from 15 premenopausal, nonpregnant women who underwent hysterectomies for benign gynecological reasons. The autophagy-associated protein, microtubule-associated protein 1 light chain 3 alpha (MAP1LC3A), was immunolocalized, and its expression level was measured by Western blot analysis. Apoptosis was evaluated by measuring the expression level of cleaved caspase 3 protein. MAP1LC3A protein was primarily expressed within the endometrial glandular cells and increased during the secretory phase. The expression level of the membrane-bound form of MAP1LC3A (MAP1LC3A-II) also increased as the menstrual cycle progressed, reaching a maximum level during the late secretory phase. This pattern coincided with the expression of cleaved caspase 3. Furthermore, expression of MAP1LC3A-II and cleaved caspase 3 increased in the in vitro-cultured endometrial cancer cells when estrogen and/or progesterone were withdrawn from the culture media to mimic physiological hormonal changes. These findings suggest that endometrial cell autophagy is directly involved in the cyclic remodeling of the human endometrium and is correlated with apoptosis. In addition, we inhibited autophagic processes using 3-methyladenine (3-MA) or bafilomycin A1 (Baf A1) to evaluate the role of autophagy in apoptosis induction in endometrial cancer cells. While the inhibition of autophagosome formation using 3-MA did not decrease apoptosis or cell death, the inhibition of autophagosome degradation by fusion with lysosomes using Baf A1 increased apoptosis and cell death, suggesting that the accumulation of autophagosomes induces apoptosis. Furthermore, Baf A1-induced apoptotic cell death was decreased by the apoptosis inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK). In conclusion, these results indicate that autophagy is involved in the endometrial cell cycle affecting apoptosis and is most prominent during the late secretory phase.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

The Role of Autophagy in Human Endometrium1

Choi

Lee

et al. 2012

Biology of Reproduction

View full text Add to dashboard Cite

show abstract

“…Cyclic variations of this marker are characterized by activation of apoptosis by the end of the secretory phase and during menstrual phase. The intensity of apoptosis in the endometrium is maximum in the late secretory, menstrual, and early proliferative phase [6].…”

Section: Resultsmentioning

confidence: 99%

Apoptosis and proliferative activity in endometrium during peritoneal endometriosis

2006

View full text Add to dashboard Cite

Apoptosis and proliferative activity of the glandular epithelium and endometrial stroma in patients with peritoneal endometriosis and in women of reproductive age without endometriosis were studied at various stages of menstrual cycle. Differences in the intensity of apoptosis were revealed manifesting in changed expression of proteins in the glandular epithelium of patients with endometriosis during the secretory phase of the menstrual cycle compared to normal. Proliferative activity of the glandular epithelium in the proliferative phase was higher than in the secretory phase. Our results suggest that the imbalance between apoptosis proteins in the endometrium plays a role in the pathogenesis of peritoneal endometriosis.

show abstract

“…Apoptotic cells are scarce during the proliferative phase of the cycle. Their proportion increases progressively during the secretory phase, peaking in the menstrual phase [9]. We recently demonstrated a gradual increase in iNOS, but not eNOS, mRNA and protein expression from the proliferative-phase towards the secretory-phase endometrium [10].…”

Section: Introductionmentioning

confidence: 91%

Elevation of Inducible Nitric Oxide Synthase Activity in Human Endometrium during Menstruation1

Tschugguel

Schneeberger

Unfried

et al. 1999

Biology of Reproduction

View full text Add to dashboard Cite

Nitric oxide (NO) is a known agonist of programmed cell death (apoptosis). In order to discover its potential role during menstrual shedding, a process associated with extensive apoptosis, we evaluated activity and mRNA levels of the inducible and constitutive isoforms of NO synthase (NOS) in endometrial specimens of the proliferative (n = 11), late-secretory (n = 7), and menstrual (n = 17) phase of the cycle. These levels were compared with the proportion of apoptotic cells by detection of histochemically labeled DNA fragments. Inducible NOS (iNOS) activity during menstruation was six times that of the proliferative or late-secretory phase (p < 0.05), whereas constitutive NOS activity remained unchanged. Competitive reverse transcription-polymerase chain reaction revealed 146% and 77% increases of iNOS mRNA expression in the late-secretory and menstrual phases, respectively, compared to the proliferative phase (p < 0.05), whereas constitutive NOS mRNA expression remained constant. Inducible NOS immunostaining was restricted to epithelial cells, whereas constitutive NOS immunostainig was confined to vascular endothelia. In addition, the proportion of apoptotic cells within the glands of late-secretory or menstrual endometrium was twice that of the proliferative phase (p < 0.05). We conclude that local production of NO is involved in the signal transduction mechanisms leading to endometrial breakdown during menstruation.

show abstract

Apoptosis in the human uterine endometrium during the menstrual cycle.

Cited by 74 publications

References 27 publications

The Role of Autophagy in Human Endometrium1

The Role of Autophagy in Human Endometrium1

Apoptosis and proliferative activity in endometrium during peritoneal endometriosis

Elevation of Inducible Nitric Oxide Synthase Activity in Human Endometrium during Menstruation1

Contact Info

Product

Resources

About