An Exploratory Study On Mechanisms Of Endometriosis-Associated Subfertility

BACKGROUND Endometriosis(EM) is the most common pelvic pathologic process that occurs in women of childbearing potential,and is associated with pain and subfertility/infertility;unfortunately,the underlying mechanisms still remain poorly understood.Studies on animals and human both indicate the implication of haptoglobin(Hp) in the pathogenesis of EM;whereas,the role of Hp in EM-related subfertility/infertility has not yet been fully investigated.OBJECTIVES To establish a rat model for endometriosis and compare ovulation and fertilization competence with sham-operated controls;to compare the expression of haptoglobin in serum and uterus of the endometriosis and control rats during gestation and determine its relation with pregnancy outcomes.METHODS The rats were autotransplanted with uterine squares as previously described,and mated;fecundity was documented as the number of day 10 embryos.Superovulation with sequential PMSG-hCG was administered to rats to evaluate the effect of surgically induced endometriosis on ovulation,fertilization and developmental competence in vitro.Haptoglobin expression in serum and eutopic endometrium during pregnancy was determined by using ELISA and real-time RT-PCR,respectively.RESULTS The autotransplanted uterine squares resulted in healthy implants with similar histological appearance with eutopic endometrium.The presence of ectopic endometrial tissue significantly reduced fecundity by 28.6% (P＜0.05).The rats with induced EM showed poor response to superovulation with fewer ova released and fertilized.Serum Hp in rats with EM was 2-fold up-regulated as compared to the controls(P＜0.001) whilst demonstrating no association with fecundity.Eutopic endometrial Hp mRNA in the rats with EM was comparable to the controls during pregnancy;whereas,a strong positive correlation was revealed between Hp mRNA level and the number of embryos implanted within the EM and the control group and in pooled population,too(P＜0.01).CONCLUSIONS Surgically-induced enodmetriosis in rats with similar pathological and physiological features to those in human offers a valuable research model to study the aspects of EM that cannot be adequately evaluated in women. Dysfunctional ovarian reserve,folliculogenesis and fertilization may be an important root cause for subfertility observed in rats with EM.Serum Hp level of specific isoforms possesses the potential of developing a novel non-invasive biomarker for the diagnosis of EM;local expression of Hp within endometrium during pregnancy is first recognized as a candidate factor to assess uterine receptivity.