Periovulatory calcium channel blockade enhances reproductive performance in an animal model for endometriosis-associated subfertility.
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In a hamster model of endometriosis-associated subfertility, periovulatory verapamil treatment reversed the complete inhibition of fertilization observed in explant-bearing animals.
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Abstract
Current evidence suggests that peritoneal inflammatory cell hyperactivation may be the essential pathologic abnormality in patients with endometriosis-associated subfertility. In these experiments we utilized an animal model to evaluate the use of an immunomodulatory agent as an alternative treatment for endometriosis-associated subfertility. The right uterine horn of 12 golden hamsters was resected and 2 x 2 mm squares were explanted onto the left uterine mesentery. Controls included hamsters undergoing uterine horn resection without endometrial explantation (n = 6) and nonsurgically treated animals (n = 6). Ovulation induction was initiated 6 weeks postoperatively with 40 IU of pregnant mare's serum gonadotropin on day 1 and 40 IU of human chorionic gonadotropin on day 3. Groups of six explant-bearing hamsters and six nonsurgical control hamsters were treated with verapamil (250 micrograms/kg every 8 hours subcutaneously), a calcium channel-blocking agent known to inhibit macrophage activation, from day 1 to 48 hours after administration of human chorionic gonadotropin. Animals were then killed and the number of embryos and oocytes in left tube counted as a reflection of reproductive performance. Fertilization was completely inhibited in animals bearing uterine explants. Treatment with verapamil dramatically reversed this effect. These data suggest that periovulatory treatment with an immunomodulatory agent such as verapamil may be an effective alternative to conventional treatment for endometriosis-associated subfertility.
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Cited by (26)
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- Endometriosis: Cell Death and Cell Signaling Machinery 2023
- Experimental endometriosis models: different approaches for different tasks 2016
- Die Wirkung von hCG auf die Dezidualisierung ektoper endometrialer Läsionen als therapeutischer Ansatz zur Behandlung der Endometriose 2014
- Effect of human interferon-alpha-2b on experimental endometriosis in rats: comparison between short and long series of treatment 2013
- Pleural Endometriosis in an Aged Rhesus Macaque ( <i>Macaca mulatta</i> ) 2011
- ROLE OF STROMAL CELL-DERIVED FACTOR-1 IN NEOANGIOGENESIS IN ENDOMETRIOSIS LESIONS 2011
- Models of Endometriosis: Animal Models I – Rodent‐Based Chimeric Models 2011
- Endometriosis research: animal models for the study of a complex disease 2010
- Endometriosis and ovarian reserve : Inflammation and prognostic markers 2008
- Combined laparoscopic surgery and pentoxifylline therapy for treatment of endometriosis-associated infertility: a preliminary trial 2008
- Baboon Model for the Study of Endometriosis 2007
- Regression of endometrial explants in a rat model of endometriosis treated with melatonin 2007
- Role of oxidative stress in endometriosis 2006
- Animal Studies in Endometriosis: A Review 2004
- Potential involvement of the immune system in the development of endometriosis 2003
- Managing endometriosis 2000
- Intraperitoneal and subcutaneous treatment of experimental endometriosis with recombinant human interferon- α-2b in a murine model 1999
- Pentoxifylline versus placebo in the treatment of infertility associated with minimal or mild endometriosis: a pilot randomized clinical trial 1997
- Immunological aspects of endometriosis 1996
- Individual and combined effects of triptoreline and gestrinone on experimental endometriosis in rats 1996
- Immune dysfunction – a potential target for treatment in endometriosis 1995
- An elicited intraperitoneal inflammatory response has no effect on the establishment of pregnancy in the mouse 1994
- 9 Endometriosis: Medical therapy 1993
- The Effect of Peritoneal Macrophage‐Derived Factor(s) on Ovarian Progesterone Secretion and LH Receptors: The Role of Calcium 1992
- Immunomodulation in the treatment of endometriosis-associated subfertility: use of pentoxifylline to reverse the inhibition of fertilization by surgically induced endometriosis a rodent model 1991
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