Clomiphene citrate and pregnancy loss

Harrison, K.; Molloy, D. William; Doody, Marylou; Breen, Terrence

doi:10.1093/oxfordjournals.humrep.a138178

Cited by 2 publications

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“…A growing number of case reports suggest that the prolonged use of clomiphene citrate (Clomid; Sanofi Aventis, Gentilly, France) is linked with bilateral ectopic pregnancy (65)(66)(67). Clomid has been widely used more than half a century by fertility clinics to induce ovulation in infertile women (65).…”

Section: Discussionmentioning

confidence: 99%

Estrogen receptor α is required for oviductal transport of embryos

O’Neill

Zhang

et al. 2017

FASEB j.

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Newly fertilized embryos spend the first few days within the oviduct and are transported to the uterus, where they implant onto the uterine wall. An implantation of the embryo before reaching the uterus could result in ectopic pregnancy and lead to maternal death. Estrogen is necessary for embryo transport in mammals; however, the mechanism involved in estrogen-mediated cellular function within the oviduct remains unclear. In this study, we show in mouse models that ciliary length and beat frequency of the oviductal epithelial cells are regulated through estrogen receptor α (ESR1) but not estrogen receptor β (ESR2). Gene profiling indicated that transcripts in the WNT/β-catenin (WNT/CTNNB1) signaling pathway were regulated by estrogen in mouse oviduct, and inhibition of this pathway in a whole oviduct culture system resulted in a decreased embryo transport distance. However, selective ablation of CTNNB1 from the oviductal ciliated cells did not affect embryo transport, possibly because of a compensatory mechanism intact CTNNB1 in the adjacent secretory cells. In summary, we demonstrated that disruption of estrogen signaling in oviductal epithelial cells alters ciliary function and impairs embryo transport. Therefore, our findings may provide a better understanding of etiology of the ectopic pregnancy that is associated with alteration of estrogen signals.-Li, S., O'Neill, S. R. S., Zhang, Y., Holtzman, M. J., Takemaru, K.-I., Korach, K. S., Winuthayanon, W. Estrogen receptor α is required for oviductal transport of embryos.

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Section: Discussionmentioning

confidence: 99%

Estrogen receptor α is required for oviductal transport of embryos

O’Neill

Zhang

et al. 2017

FASEB j.

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“…anovulatory infertility increases the risk of tubal ectopic pregnancy [10][11][12], we investigated the molecular and cellular processes underlying this phenomenon. The notion that chronic treatment with CC in rats induces apoptosis of tubal epithelial cells in the isthmus through a mitochondria-dependent signaling pathway was obvious.…”

Section: Downloaded From Wwwbiolreprodorgmentioning

confidence: 99%

“…Although CC has limited dose-dependent side effects, prolonged treatment is associated with an increased frequency of tubal ectopic pregnancy in humans [10][11][12], raising the possibility such treatment causes fallopian tube abnormalities. Therefore, elucidating the molecular and cellular mechanisms for the fallopian tube-specific effects of CC is important for enhancing its therapeutic efficacy against infertility and preventing adverse effects.…”

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

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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

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Clomiphene citrate and pregnancy loss

Cited by 2 publications

References 0 publications

Estrogen receptor α is required for oviductal transport of embryos

Estrogen receptor α is required for oviductal transport of embryos

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

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