Ovulation Success Research Articles

In this issue - September 2016: Portable negative pressure wound therapy for skin grafts in dogs · Wellness testing in small animals · Effects of pimobendan on myocardial perfusion and pulmonary transit time in dogs · Rispens CVI988 vaccine virus and Marek's disease virus in poultry · A field study of ovulation in oestrus mares · Post-weaning growth of beef

In this issue - September 2016: Portable negative pressure wound therapy for skin grafts in dogs · Wellness testing in small animals · Effects of pimobendan on myocardial perfusion and pulmonary transit time in dogs · Rispens CVI988 vaccine virus and Marek's disease virus in poultry · A field study of ovulation in oestrus mares · Post-weaning growth of beef

Ovulation and spawning induction in Caspian kutum Rutilus frisii kutum by administration of GnRHa and catecholaminergic pharmaceutical compounds with Ovaprim

The acceleration of final oocyte maturation and ovulation is recognized as a principal process in Caspian kutum Rutilus frisii kutum, a commercial and valuable species in Caspian Sea. The aim of this study was to evaluate the effects of catecholaminergic pharmaceutics which include Salbutamol (β2-adrenergic receptor agonist), Metoprolol (β1-adrenergic receptor antagonist), Clozapine and Olanzapine (the third generation of D4 and D2 dopamine receptor antagonists) which can be more efficient than the first and second generations, in combination with Buserelin ([D-Ser(tBu)6,Pro9-NEt]-GnRHa) and Ovaprim (D-Ala6,Pro9-Net)-sGnRH+Domperidone on ovulation and spawning induction in Caspian kutum. One hundred eight adult females were injected once with Buserelin Acetate (BUS) 5 μg kg−1 BW, Ovaprim 0.5 mL kg−1 BW, Salbutamol Sulphate (SLB) 4 mg kg−1 BW, Olanzapine (OLZ) 5 mg kg−1 BW, Clozapine (CZ) 12 mg kg−1 BW and Metoprolol Tartrate (MTP) 5 mg kg−1 BW, being divided into 12 groups: group 1, intact (negative control); group 2, Ovaprim (positive control); group 3, OLZ+SLB; group 4, OLZ+MTP; group 5, OLZ+BUS; group 6, CZ+SLB; group 7, CZ+MTP; group 8, CZ+BUS; group 9, OLZ+BUS+SLB; group 10, OLZ+BUS+MTP; group 11, CZ+BUS+SLB and group 12, CZ+BUS+MTP (N = 9). The results showed that the highest mean value in ovulation success, ovulation index, fertilization success, relative fecundity and the number of eggs belonged to Ovaprim treatment. On the other hand, spawning was successful in OLZ+BUS+SLB and CZ+BUS treatments (P < 0.05), whereas it was lower in CZ+MTP, CZ+BUS+MTP and OLZ+BUS than the other treatments. Therefore, it could be concluded that Clozapine and Olanzapine potentiated the effect of Buserelin treatment in ovulation and spawning induction, while Metoprolol blocked the stimulatory effects of GnRHa, Clozapine and Olanzapine. Salbutamol also can amplify stimulatory effect of all mentioned pharmaceutics.

Is Anxiety an Effective Factor on the Success of Ovulation Induction/Intrauterine Insemination Cycle?

Is Anxiety an Effective Factor on the Success of Ovulation Induction/Intrauterine Insemination Cycle?

Effect of antiprogesterone RU486 on VEGF expression and blood vessel remodeling on ovarian follicles before ovulation.

BackgroundThe success of ovarian follicle growth and ovulation is strictly related to the development of an adequate blood vessel network required to sustain the proliferative and endocrine functions of the follicular cells. Even if the Vascular Endothelial Growth Factor (VEGF) drives angiogenesis before ovulation, the local role exerted by Progesterone (P4) remains to be clarified, in particular when its concentration rapidly increases before ovulation.AimThis in vivo study was designed to clarify the effect promoted by a P4 receptor antagonist, RU486, on VEGF expression and follicular angiogenesis before ovulation, in particular, during the transition from pre to periovulatory follicles induced by human Chorionic Gonadotropins (hCG) administration.Material and MethodsPreovulatory follicle growth and ovulation were pharmacologically induced in prepubertal gilts by combining equine Chorionic Gonadotropins (eCG) and hCG used in the presence or absence of RU486. The effects on VEGF expression were analyzed using biochemical and immunohistochemical studies, either on granulosa or on theca layers of follicles isolated few hours before ovulation. This angiogenic factor was also correlated to follicular morphology and to blood vessels architecture.Results and ConclusionsVEGF production, blood vessel network and follicle remodeling were impaired by RU486 treatment, even if the cause-effect correlation remains to be clarified. The P4 antagonist strongly down-regulated theca VEGF expression, thus, preventing most of the angiogenic follicle response induced by hCG. RU486-treated follicles displayed a reduced vascular area, a lower rate of endothelial cell proliferation and a reduced recruitment of perivascular mural cells. These data provide important insights on the biological role of RU486 and, indirectly, on steroid hormones during periovulatory follicular phase. In addition, an in vivo model is proposed to evaluate how periovulatory follicular angiogenesis may affect the functionality of the corpus luteum (CL) and the success of pregnancy.

IMPACT OF OOCYTE SIZE ON LHRHa INDUCED OVULATION AND FERTILIZED EGG QUALITY IN SADDLED BREAM OBLADA MELANURA (LINNAEUS, 1758)

The objective of this study was to evaluate the effects of oocyte size and luteinizing hormone releasing hormone analogue (LHRHa) on ovulatory success in artificial fertilization. Vitellogenic females with maximum oocyte diameters 400-550 μm were repeatedly injected with LHRHa (20 μ g kg-1 per injection). Fish with maximum oocyte diameters 500 μm spawned within 48-54 h. These results demonstrate that injected LHRHa is effective for ovulation of saddled bream with maximum oocyte diameters >500μm.

Metformin-clomiphene citrate vs. clomiphene citrate alone: Polycystic ovarian syndrome

BACKGROUND:Polycystic ovary syndrome (PCOS) is the commonest endocrinopathy in women that is associated with reproductive and metabolic disorders.OBJECTIVES:We compared the ovulation and conception rates after the treatment with clomiphene citrate (CC) alone and in combination with metformin in infertile patients presented with polycystic ovarian syndrome (PCOS).MATERIALS AND METHODS:This randomized controlled trial of independent cases and controls was conducted at the Department of Obstetrics and Gynecology, Hera General Hospital, Makkah, Saudi Arabia from February 01 to December 31, 2008. The 42 subjects diagnosed as PCOS were divided into group A and B (21 subjects in each) for management with CC + metformin and CC alone, respectively. Group A received 500 mg three times a day of metformin continuously from the first cycle for 6 months or till pregnancy was confirmed. In both groups CC was started at a dose of 50 mg from day-2 till day-6 of the menstrual cycle. The dose of CC was increased to 100 mg in second and 150 mg in third cycle, and then remained 150 mg for the remaining three cycles. With ovulation the dose of CC was unaltered in both groups. Data were analyzed using Statistical Package for the Social Sciences (SPSS) version 16.RESULTS:More than 50% females in both groups were had body mass index > 25. Group A achieved high rate of regular cycles, ovulation success, and conception than group B (71.4% vs. 38.1%; P = 0.03), (76.2% vs. 38.1%; P = 0.021), and (66.6% vs. 28.6%; P = 0.01), respectively.CONCLUSION:Management with metformin + CC increased the ovulation and conception rates.

17β-Estradiol is critical for the preovulatory induction of prostaglandin E2 synthesis in mice

Aromatase-deficient (ArKO) mice are totally anovulatory due to insufficient estrogen production. However, sequential administrations of high doses of 17β-estradiol (E2) and gonadotropins were found to induce ovulation in these mice. Here, we examined how the ovulatory stimulation for ArKO mice alters the expressions of genes related to prostaglandin (PG) E2 metabolism and ovarian contents of PGE2, as PGE2 is one of the critical mediators of ovulatory induction. The ovulatory stimulation significantly increased mRNA expressions of prostaglandin-endoperoxide synthase 2, PGE2 receptor type 4 and sulfotransferase family 1E, member 1, in preovulatory ArKO ovaries. In contrast, it suppressed the mRNA expression of 15-hydroxyprostaglandin dehydrogenase. Furthermore, significant elevation in the PGE2 contents was detected in the preovulatory ovaries of ArKO mice after stimulation with E2 plus ovulatory doses of gonadotropins. Thus, these analyses demonstrate a requirement of E2 for the preovulatory enhancement of PGE2 synthesis, leading to future success in ovulation.

Use of Channel Catfish, Ictalurus punctatus, Pituitary as a Spawning Aid: Influence of Seasons and Preparations on Efficacy

Channel catfish, Ictalurus punctatus, pituitary powder (CP) was prepared and administered to determine the effect of pituitary preparation, head selection criteria, and season of collection on the biological potency of this gonadotropic preparation. Pituitaries were harvested from three catfish processing plants throughout the months of December, February, March, and April to investigate the effect of season on CP potency. Gravid female channel catfish were injected intraperitoneally (IP) with priming (2 mg/kg) and resolving doses (8 mg/kg) of CP treatments, luteinizing hormone-releasing hormone analog (LHRHa), or saline. Pharmaceutical grade Carbopol 971P resin (CAR) was tested as a 1% aqueous dispersion in physiological saline and administered with CP (10 mg/kg) as a IP single injection at a final volume of 2 mL per kg as a slow-release vehicle. Individual females were hand-stripped, and eggs were fertilized with freshly harvested blue catfish, Ictalurus furcatus, spermatozoa. Pituitaries processed with either acetone or ethanol/acetone resulted in significantly different ovulation rates of 35 and 73%, respectively (P≤ 0.01). Ovulation success was not significantly different among CP and LHRHa treatment groups. Ovulation rates were not significantly different among treatment groups of CP collected in April (74%) or December (67%), or collected from male (69%), or small individuals (55%). The shortest latency period among CP treatment was from CP collected in December and from males at 39.1 ± 0.7 and 38.5 ± 0.4 h, respectively. The CAR vehicle treatment performed poorly resulting in an average ovulation rate of 19.0%, with 3.3% viable embryos at 36 h post-fertilization. Pituitaries collected from channel catfish potentially represent a viable spawning aid for the production of hybrid channel × blue catfish.

Dopamine control of LH release in the tench ( Tinca tinca)

Tench ( Tinca tinca) is apparently the only known member of the Cyprinidae in which ovulation is stimulated following administration of a low dose of GnRH analogue (GnRHa) without a dopamine inhibitor. This study evaluated LH release effectiveness of the most commonly used GnRHa and clarified whether LH secretion followed by ovulation is subject to inhibitory dopaminergic control in tench. Fish were intraperitoneally injected with three types of GnRHa, GnRHa with dopamine inhibitor metoclopramide (combined treatment), or the dopamine inhibitor metoclopramide alone. LH concentrations at five sampling times (0, 6, 12, 24, and 33 h) together with ovulation success and fecundity index were recorded. The combined treatment triggered an almost immediate LH release peak with a gradual decline, and resulted in a high ovulation rate. In contrast to the combined treatment, an application of GnRHa alone at 10 μg kg −1 induced gradual increase of LH concentrations with peaks close to ovulation time, and with high ovulation success. Significant differences in LH concentrations at 6 and 12 h and no differences in ovulation success were found between the combined and the GnRHa alone treatments. Metoclopramide alone induced a small increase in LH with no ovulation. The study presents clear evidence of dopaminergic control of LH release in tench, with a high ovulation rate obtained after application of GnRHa alone or in combination with dopamine inhibitor.

Comparison of the effects of different methods of mammalian and salmon GnRHa administration on spawning performance in wild-caught female carp ( Cyprinus carpio carpio) from the Caspian Sea

The effects of acute or sustained administration of mammalian and salmon GnRH agonists (mGnRHa and sGnRHa) were examined on the reproduction performance of wild-caught female carp from the Caspian Sea. Ripe broodfish were caught in the beginning of spawning season (early May) by seine from the southeast coastal waters of the Caspian Sea, Golestan province, Iran. To induce spawning fish were allocated into 8 groups and treated with 7% physiological saline (control), 4 mg kg − 1 carp pituitary (CP) extract (positive control), 20 μg kg − 1 mGnRHa or sGnRHa together with 40 mg kg − 1 Metoclopramide (acute treatments), a cholesterol pellet containing 20 μg kg − 1 mGnRHa or sGnRHa together with 40 mg kg − 1 Metoclopramide, and emulsified GnRHa in Freud's Incomplete Adjuvant (FIA) containing 20 μg kg − 1 mGnRHa or sGnRHa together with 40 mg kg − 1 Metoclopramide (mGnRHa-FIA and sGnRHa-FIA). After the final injection the fish were checked for spawning regularly. Ovulated fish were stripped manually and the eggs fertilized artificially. Significant differences were observed in the reproduction success, latency period and practical fecundity among treated groups ( p ≤ 0.05). Injection of CP or sGnRHa in acute or sustained methods increased significantly the reproduction success compared to acute injection, implanting of mGnRHa or controls ( p ≤ 0.05). In spite of the weaker effect of mGnRHa injection or cholesterol implant on induction of ovulation, treatment with mGnRHa-FIA showed similar effects as sGnRHa-FIA. Almost all sustained delivery systems of both GnRHa enhanced the practical fecundity of treated fish compared to CP and acute GnRHa injections. The latency periods of fish that received GnRHa-FIA and implant were near 24 and 50 h, respectively, which were significantly longer than that of fish given an acute GnRHa treatment or CP ( p ≤ 0.05). There was no significant difference in fertilization and hatching success of the produced progeny among treated groups ( p ≥ 0.05). The results showed that injection of GnRHa in FIA increased significantly the ovulation success of fish, but implanting fish with mGnRHa in a cholesterol pellet had variable effects with increasing fecundity but not higher ovulation success, compared to the CP treatment.

Induced ovulation in cultured tawny puffer Takifugu flavidus by injections of LHRH-a

To determine the effective LHRH‐a dosage for cultured tawny puffer ovulation, the effects of 10, 30, 50, and 70 I¼g kg−1 body weight (BW) LHRH‐a were tested with two injections in 2009, and by a single injection (5, 10, 30, 50, and 70 I¼g kg−1 BW) in 2010. Ovulation success and egg quality were assessed. All females spawned after being treated with 10 to 70 I¼g kg−1 BW LHRH‐a in 2009 and 2010. Ovulation success was only 20.0% with the 5 I¼g kg−1 BW treatment, significantly lower (P   0.05) among the 10, 30, 50, and 70 I¼g kg−1 BW treatment groups in terms of ovulation success, ovulation time, egg production, fertilization rate, hatch rate, and viability of 24 h post‐hatch larvae in 2009 and 2010. None of the treatments caused any mortality among the females during the experimental periods. Results suggest that the treatment using only LHRH‐a effectively and reliably induces ovulation in cultured tawny puffer broodstocks, whether through a single injection or through two injections. Effective and most economical dosage of LHRH‐a is 10 I¼g kg−1 BW. Determination of the effective LHRH‐a dosage is an important step in the development of tawny puffer fish culture.

Effective dose of mGnRHa for induction of ovulation in tench ( Tinca tinca L.)

The present study was designed to investigate the in vivo dose-response of mammalian GnRH analogue [ d-Ala 6, Pro 9, NEthylamide]-mGnRH in stimulating a pre-ovulatory LH surge and subsequent ovulation in female tench. Five doses of mGnRHa (1, 2.5, 5, 10, and 20 μg kg − 1 ) and a control group (0.9% NaCl) were tested under hatchery conditions. Concentration of plasma LH and ovulation success were evaluated. All mGnRHa treatments yielded significantly higher LH levels and ovulation success compared to control. The only difference in LH levels was a higher level with 10 μg kg − 1 at 24 h post-treatment. No differences were observed in ovulation success (≥ 60% of females) among mGnRHa treatments. However, non-linear regression analyses indicated increasing LH concentration and ovulation rate with increasing mGnRHa dosage. This trend implies that dosages in the range of 10–20 μg kg − 1 of mGnRHa can be considered reliable and effective concentrations.

Estradiol, testosterone, 11-ketotestosterone, 17, 20β-dihydroxy-4-pregnen-3-one and vitellogenin plasma levels in females of captive European sturgeon, Acipenser sturio

Summary The changes for plasma level of sex steroid hormones and vitellogenin (VTG) during oogenesis and at ovulation are studied in the aim of being potentially used as predictive markers of breeding performance in sturgeon species. In the present work we describe the development of plasma steroid hormones and vitellogenin (VTG) profiles in three females which were followed over 5 years and approaching the spawning, and we focus on the months preceding the spawning induction. Plasma estradiol (E2), testosterone (T), 11-ketotestosterone (11KT), 17, 20b dihydroxy-4-pregnen-3one (17, 20bP) and vitellogenin (VTG) are measured by Enzyme Linked Immuno Sorbant Assay (ELISA). During the 5-year period study, hormonal profile varies differently from one female to the other, linked to stage of development of the ovary. High levels of E2 and VTG are found, although restricted to the years when oocytes develop. There is some seasonal variation, with a peak of E2 at the end of winter, and a dramatic decrease in May. During months before the spawning induction, E2 levels are decreasing, while VTG remains at high level, 11KT sharply increases while 17, 20bP increases 20 to hundred fold during the same time. Only one female achieves GVBD that triggered ovulation and gives fertile eggs. The comparison of the three females is a first step aiming at correlating some of the plasma parameters to the success of hormone-induced ovulation in this highly endangered species.

Predictors of Pregnancy in Women With Polycystic Ovary Syndrome

Two professional medical societies used expert opinion as the basis for their recommendation that current first-line treatment of polycystic ovary syndrome (PCOS)-related infertility should be ovulation induction with the selective estrogen receptor modulator, clomiphene citrate (CC), for up to 6 ovulatory cycles, with the addition of the insulin sensitizer metformin only for glucose intolerance. This prospective, multicenter, randomized clinical trial was designed to determine which baseline patient characteristics among women with PCOS were predictive of success of fertility treatment in 4 clinically relevant prognostic models of ovulation, conception, pregnancy, and live birth. Live birth was the primary study outcome. Between 2002 and 2004, ovulation was induced in 626 infertile women with PCOS by either CC plus placebo (n = 209), metformin plus placebo (n = 208), or combination CC plus metformin (n = 209). The factors that were significant for prediction of treatment success in all 4 conception models were body mass index, baseline free androgen index, proinsulin level, and duration of attempting conception. History of a prior pregnancy loss was predictive of treatment success in the models for ovulation and conception, but was not predictive of pregnancy or live birth. A low hirsutism score (<8) was not predictive of ovulation success, but was predictive of conception, pregnancy, and live birth. Age had divergent effects on ovulation and pregnancy outcomes. Age 34 or younger was a predictive factor for a successful pregnancy and live birth, whereas age greater than 34 years was predictive only of successful ovulation. Smoking history was not a significant predictor. These findings may be useful to counsel women with PCOS on their likelihood for live birth and to select infertility therapy.

Predictors of Pregnancy in Women with Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. The selection of first-line therapies for ovulation induction is empiric. The aim of the study was to develop a clinically useful predictive model of live birth with varying ovulation induction methods. We built four prognostic models from a large multicenter randomized controlled infertility trial of 626 women with PCOS performed at academic health centers in the United States to predict success of ovulation, conception, pregnancy, and live birth, evaluating the influence of patients' baseline characteristics. Ovulation was induced with clomiphene, metformin, or the combination of both for up to six cycles or conception. The primary outcome of the trial was the rate of live births. Baseline free androgen index, baseline proinsulin level, interaction of treatment arm with body mass index, and duration of attempting conception were significant predictors in all four models. History of a prior loss predicted ovulation and conception, but not pregnancy or live birth. A modified Ferriman Gallwey hirsutism score of less than 8 was predictive of conception, pregnancy, and live birth (although it did not predict ovulation success). Age was a divergent predictor based on outcome; age greater than 34 predicted ovulation, whereas age less than 35 was a predictive factor for a successful pregnancy and live birth. Smoking history had no predictive value. A live birth prediction chart developed from basic clinical parameters (body mass index, age, hirsutism score, and duration of attempting conception) may help physicians counsel and select infertility treatments for women with PCOS.

Artificial off-season spawning of Eurasian perch Perca fluviatilis L.

The aim of the study was to conduct off-season spawning of perch, Perca fluviatilis L. Spawners were obtained in late September from Lake Kortowskie. The fish were transported to the hatchery and divided into two size groups: G1 - small fish (30-70 g), and G2 - large fish (200-400 g). All males from G1 group spermiated after a two-month period of photo-thermal stimulation, but only 25% of the males from G2 group produced milt. Better results were obtained with fish that were stimulated after three months of chilling. All the stimulated males spermiated and produced higher volumes of milt. The best results, defined as ovulation success and embryo survival to the eyed-egg-stage, as well as spawner survival rate, were obtained with large females (G2-B) stimulated with a double dose of hormone (2 Ovopel pellets kg -1 ). The egg strands obtained from females from group A (small and large fish stimulated with GnRHa and metoclopramide at 0.1 and 1 pellet kg -1 after 24 hr) were usually fragmented. All females responded to the hormonal injections after 4 to 5 days.

Elevated day-3 follicle-stimulating hormone (FSH) in women younger than 35 years: can it predict success in ovulation induction/intrauterine insemination (OI/IUI) cycles?

OBJECTIVE: To determine the predictive value of day 3 FSH on clinical pregnancy and spontaneous abortion rates in women younger than 35 years treated with ovulation induction/intrauterine insemination.

Genetics of Ovulation

Ovulation is essential for reproductive success; many cases of infertility in women may be related to disruption of this critical and complex ovarian process. Recent gene profiling studies using rat, mouse, and human ovaries and cumulus oocyte complexes isolated prior to, during, and following luteinizing hormone (LH or human chorionic gonadotropin) -induced ovulation have unmasked a surprising diversity and staggering number of genes for which expression is altered in these tissues. Thus, impairment of this process could involve many factors not yet considered. Although some genes associated with inflammatory-like responses have been identified previously and shown to be obligatory for ovulation, others represent entirely new categories of genes. These include genes associated with innate immune responses and immune cell functions, neuronal cell activity, and novel signaling cascades. The innate immune and neuronal genes are expressed in cumulus cells not adhering immune cells. Thus, cumulus cells acquire immune cell-related functions. The neuronal-related genes may influence cumulus cell migration during formation of the hyaluronan-rich matrix. The factors stabilizing the matrix are essential for expansion of the cumulus oocyte complex and release of a fertilizable oocyte contained therein. Novel signaling molecules include members of the WNT/FRIZZLED family, the BMP family, and transcription factors. Some of these novel genes may become useful predictors of ovulation success and/or embryo health and viability.

The use of luteinizing hormone releasing hormone analogue for ovulation induction in black sea bass ( Centropristis striata)

Interest in commercial production of black sea bass has increased in recent years, but reliable spawning methods remain problematic. The objective of this study was to evaluate the effects of oocyte size and luteinizing hormone releasing hormone analogue (LHRHa) dosage and delivery systems on ovulatory success for in vitro fertilization. Vitellogenic females with maximum oocyte diameters of 400–625 μm were implanted with a 95% cholesterol–5% cellulose pellet containing 50 μg of LHRHa. Fish with maximum oocyte diameters < 450 μm failed to ovulate. In contrast, 90% of fish with 500 μm oocytes spawned within 36 h and 40% of this group ovulated a second time. All of the females containing oocytes > 550 μm ovulated. In a second experiment, females with uniformly vitellogenic oocytes (> 500 μm) and implanted with 50 μg LHRHa ovulated substantial numbers of eggs (45,000–192,000 eggs/kg body weight (BW), but fertility was consistently low (0–15%). In a third experiment, 19 of 39 females receiving implants containing 6.3–23.6 μg LHRHa/kg BW during the spawning season ovulated, but fecundity (17,000–339,000 eggs/kg) and fertilization (0–98%) were highly variable. When fish were grouped by developmental index, calculated as the number of oocytes with diameters > 400 μm/total number of oocytes measured, there were no statistical differences among groups with respect to the number of spawns, fecundity or fertilization success. In a fourth experiment, 11 of 13 females with a clutch of fully vitellogenic oocytes that were injected with 20 or 100 μg/kg BW LHRHa ovulated between 1 and 2 times on consecutive days. Five of seven given an implant containing 12.5 μg LHRHa ovulated one or more times. Fish implanted with shams or injected with vehicle alone did not ovulate in any of the experiments. No differences were found in the number of spawns, fecundity or fertilization success from fish receiving different doses of injected or implanted LHRHa. Incubation of pooled eggs produced 155,000 larvae (60% hatch) and 95,000 one-gram juveniles. These results demonstrate that injected or implanted LHRHa is effective for inducing ovulation in black sea bass with maximum oocyte diameters > 500 μm.

026. The cumulus matrix in ovulation: inert packaging or active delivery vehicle for the oocyte?

Preovulatory follicles respond to the LH-surge with a cascade of molecular events. The ovulatory signal initially impinges on the mural granulosa layers triggering rapid tissue morphogenesis and ultimately terminal differentiation of these cells. Mural granulosa cells transiently produce a suite of transcriptional regulators, EGF-like ligands as well the extracellular matrix (ECM) proteoglycan, versican and the protease ADAMTS-1. These act in concert with permissive oocyte signals to induce and organise a complex hyaluronan (HA) rich ECM surrounding the cumulus cells and oocyte. This expanded cumulus matrix is analogous in composition to an extensive form of pericellular matrices actively associated with cell migration. During ovulation the cumulus matrix becomes anti-adhesive to the intra-follicular environment but is strongly pro-adhesive for the oviductal fimbria. When the follicle apex is perforated the COC is released binds to the fimbria and transports into the oviduct where fertilisation occurs. Success of ovulation and fertilisation is sensitive to the appropriate production and assembly of cumulus matrix components that are in turn dependent on an appropriate balance of oocyte and granulosa derived signals. Production of these cumulus matrix components is thus a potential checkpoint that assures ovulation of competent oocytes. The HA matrix is cross-linked by organiser molecules and also is enriched in proteases ADAMTS-1, 4, 5. Although these have potentially redundant functionality, ADAMTS-1 null female mice are profoundly sub-fertile and have reduced ovulation rate. Specific components of the cumulus matrix are disorganised in ADAMTS-1 null mice and cleavage of versican in these cumulus complexes is reduced. Thus ADAMTS-1 and versican have unique roles in normal cumulus matrix expansion that is important for ovulation. Altered interaction of the cumulus complex with neighbouring tissues alters transport through the oviduct, while abnormal persistence of COC matrix structure after ovulation is also likely to impair sperm interaction and penetration. Evidence thus indicates that the expanded cumulus matrix plays several active roles in oocyte release, transport and sperm interaction.