Clomiphene citrate inhibits gonadotropin-induced ovulation by reducing cyclic adenosine 3′,5′-cyclic monophosphate and prostaglandin E2 levels in rat ovary

Chaube, Shail K.; Prasad, Pramod Vishwanath; Tripathi, Vineeta; Shrivastav, Tulsidas G.

doi:10.1016/j.fertnstert.2006.03.027

Cited by 16 publications

(15 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Clomiphene citrate has antagonistic activity on estrogen/ estrogen receptor (ESR) signaling in female reproductive tissues, including rodent ovary [13,14], chicken fallopian tube [15], and human endometrium [16][17][18][19], and it acts as a strong agonist in nonreproductive tissues, such as bone and liver [20]. In rats, CC induces apoptosis of ovarian granulosa cells that can be rescued by 17b-estradiol (E2) in vivo [21,22].…”

Section: Introductionmentioning

confidence: 99%

Clomiphene Citrate Causes Aberrant Tubal Apoptosis and Estrogen Receptor Activation in Rat Fallopian Tube: Implications for Tubal Ectopic Pregnancy1

Shao

Nutu

Weijdegård

et al. 2009

Biology of Reproduction

View full text Add to dashboard Cite

Clomiphene citrate (CC) therapy for disorders of anovulatory infertility has been linked to an increased frequency of tubal ectopic pregnancy. Although CC enhances apoptotic processes in the ovaries, villi, and decidual tissues, its effect on apoptosis in the fallopian tube is unknown. Here, we show that chronic treatment with CC induces tubal apoptosis, but not necrosis, through an intrinsic mitochondria-dependent signaling pathway in vivo. The apoptosis was specific to epithelial cells in the isthmus, and the damage was reversed with 17beta-estradiol (E2); however, pretreatment or concomitant treatment with E2 did not protect against tubal apoptosis induced by chronic treatment with CC. Chronic treatment activated estrogen receptors (ESRs), particularly cilia-localized ESR2A (formerly ERbeta2). In contrast to E2, acute treatment of superovulating rats with a high dose of CC or the ESR2-selective agonist 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN) significantly delayed the transport of oocyte-cumulus complexes through the fallopian tube. Our findings suggest that in response to chronic CC therapy, isthmus-specific apoptosis of epithelial cells and activation of cilia-ESR2A act in parallel to block gamete and embryo passage through the fallopian tube, eventually resulting in tubal ectopic pregnancy.clomiphene citrate, ectopic pregnancy, estradiol receptor, estrogen receptor, fallopian tubes, intrinsic and extrinsic apoptotic pathways

show abstract

Section: Introductionmentioning

confidence: 99%

Clomiphene Citrate Causes Aberrant Tubal Apoptosis and Estrogen Receptor Activation in Rat Fallopian Tube: Implications for Tubal Ectopic Pregnancy1

Shao

Nutu

Weijdegård

et al. 2009

Biology of Reproduction

View full text Add to dashboard Cite

show abstract

“…The anti-estrogenic effects of CC and the mechanism by which CC exerts its direct action at the level of ovary remains poorly understood. One study suggest that CC induces apoptosis in human granulosa cells cultured in vitro [26] and reduces estradiol 17β as well as progesterone synthesis in rat [33] and in humans [26] [34]. These finding were further supported by animal studies that CC induces granulosa cell apoptosis and reduced level of estradiol 17β in ovary as well as circulation in rat [32] [35] as well as in monkey [36].…”

Section: Clomiphene Citrate-induced Apoptosismentioning

confidence: 86%

Clomiphene Citrate Induces ROS-Mediated Apoptosis in Mammalian Oocytes

Chaube¹,

Shrivastav²,

Prasad³

et al. 2014

OJApo

Self Cite

View full text Add to dashboard Cite

The clomiphene citrate (CC), a nonsteroidal triphenylethylene compound, is a first line of medicine used for the induction of ovulation in anovulatory women worldwide. In spite of high ovulation induction with the use of CC, the pregnancy rate is much lower. Such a discrepancy could be due to the peripheral anti-estrogenic effect of CC, particularly at the level of ovary, endometrium and cervical mucus. CC induces ovulation by binding to the estrogen receptors and generates hypoestrogrnic state in hypothalamus leading to release of pituitary gonadotropins. CC may have a direct effect at the level of ovary but the molecular mechanism remains unclear. Animal studies suggest that the CC induces apoptosis in granulosa cells and results hypoestrogenic state in the ovary. Reduced estradiol 17β level in the ovary affects development and maturation of oocyte leading to oocyte apoptosis. Further, CC increases hydrogen peroxide (H2O2) level and thereby bax protein expression and DNA fragmentation in cumulus-granulosa cells as well as in oocytes. The exogenous supplementation of either estradiol 17β or melatonin reduces H2O2 level in ovary, delays meiotic cell cycle progression in oocyte and protects oocyte apoptosis. Hence, supplementation of estradiol 17β or melatonin along with CC could be beneficial to protect granulosa cell as well as oocyte apoptosis and inhibit deterioration of oocyte quality. Thus, maintenance of oocyte quality may overcome the adverse effect caused due to CC treatment during infertility management.

show abstract

“…It is unlikely that raising LH levels alone plays a role in cluster headache prevention as LH levels were markedly reduced in the study subjects who responded to leuprolide. In addition to altering testosterone and LH levels, clomiphene citrate has been shown to reduce prostaglandin E2 levels in a rat model of ovulation and also in human endometrial cells 12,13 . Prostaglandins are known to have vasoactive properties and serum prostaglandin E2 levels are elevated during cluster headache cycles 14 .…”

Section: Discussionmentioning

confidence: 99%

Clomiphene Citrate for Treatment Refractory Chronic Cluster Headache

Rozen¹

2007

Headache

View full text Add to dashboard Cite

A treatment refractory chronic cluster headache patient is presented who became cluster-free on clomiphene citrate. The author has previously reported a SUNCT patient responding to clomiphene citrate. Hypothalamic hormonal modulation therapy with clomiphene citrate may become a new preventive choice for trigeminal autonomic cephalalgias. The possible mechanism of action of clomiphene citrate for cluster headache prevention will be discussed.

show abstract

Clomiphene citrate inhibits gonadotropin-induced ovulation by reducing cyclic adenosine 3′,5′-cyclic monophosphate and prostaglandin E2 levels in rat ovary

Cited by 16 publications

References 34 publications

Clomiphene Citrate Causes Aberrant Tubal Apoptosis and Estrogen Receptor Activation in Rat Fallopian Tube: Implications for Tubal Ectopic Pregnancy1

Clomiphene Citrate Causes Aberrant Tubal Apoptosis and Estrogen Receptor Activation in Rat Fallopian Tube: Implications for Tubal Ectopic Pregnancy1

Clomiphene Citrate Induces ROS-Mediated Apoptosis in Mammalian Oocytes

Clomiphene Citrate for Treatment Refractory Chronic Cluster Headache

Contact Info

Product

Resources

About