Follicular fluid renin concentration and IVF outcome

Cornwallis, Caroline; Skinner, Sandford L.; Nayudu, P.L.; Lopata, Alexander; Thatche, R.L.; Yeung, S; Whitworth, J. A.

doi:10.1093/oxfordjournals.humrep.a137113

Cited by 16 publications

(7 citation statements)

References 10 publications

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“…Ang II has been also shown to promote progesterone-induced maturation in oocytes from Xenopus laevis by mobilizing Ca2+ via a signal transferred through the gap junctions between the follicular cells and the oocyte (48). Recent data derived from the in vitro fertilization program in humans demonstrate that the prorenin concentration in the follicular fluid is correlated with follicular development, oocyte-cumulus complex maturity, and oocyte viability, resulting in successful pregnancy (49,50). These observations, in conjunction with data showing the immunolocalization of angiotensin converting enzyme in the rabbit oolemma (51 ), suggest that the ovarian RAS may be involved in the process of maturation of mammalian oocyte as well.…”

Section: Resultsmentioning

confidence: 99%

Gonadotropin stimulates ovarian renin-angiotensin system in the rabbit.

Yoshimura¹,

Koyama²,

Karube³

et al. 1994

J. Clin. Invest.

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The present study was undertaken to assess the role of ovarian renin-angiotensin system (RAS) in the preovulatory cascade induced by gonadotropin exposure. In the in vitro perfused rabbit ovaries, exposure to human chorionic gonadotropin (hCG) enhanced the secretion rate of angiotensin II (Ang II) within 1 h. The secretion rate reached maximal levels at 6 h and then declined thereafter. The intrafollicular Ang II content and renin-like activity were also significantly increased at 2 and 4 h after exposure to hCG, compared with control ovaries perfused with medium alone. The level of intrafollicular Ang II after hCG exposure significantly exceeded the concentration of Ang II in an equivalent volume of plasma. The addition of 1 ,uM captopril to the perfusate significantly inhibited the secretion rate of Ang II stimulated by hCG; however, captopril affected neither the ovulatory efficiency nor prostaglandin production in ovaries treated with hCG. Captopril significantly inhibited the resumption of meiosis in the ovulated ova and follicular oocytes stimulated by hCG. The administration of 100 ,ug Ang II at 2-h intervals to the perfusate reversed the inhibitory effects of captopril on hCG-induced oocyte maturation. In conclusion, these data indicate that gonadotropin stimulates renin-like activity and Ang11 production in the rabbit ovary. Ovarian renin-angiotensin system may play an important role in the process of oocyte maturation after exposure to gonadotropin. (J.

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Section: Resultsmentioning

confidence: 99%

Gonadotropin stimulates ovarian renin-angiotensin system in the rabbit.

Yoshimura¹,

Koyama²,

Karube³

et al. 1994

J. Clin. Invest.

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“…Derkx et al 1987). The concentration has been shown to relate to the outcome of in vitro fertilization (Cornwallis et al 1990;Itskovitz et al 1991). In humans, plasma prorenin was shown to increase in relation to ovulation and stimulation with gonadotropins (Sealey et al 1985;Itskovitz et al 1987).…”

Section: Introductionmentioning

confidence: 99%

Measurement and Identification of Prorenin and Renin in Ovarian Follicular Fluid From Cattle and Pig

Hagemann¹,

Nielsen²,

Dantzer³

et al. 1992

Clin Exp Pharma Physio

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1. In previous studies we have demonstrated and solved several methodological problems in relation to the measurement of prorenin by trypsin activation in rat, bovine, hog and horse plasma. 2. The aim of the present study was to develop a method for the measurement of prorenin in bovine and porcine ovarian follicular fluid. 3. Trypsin activation of follicular fluid generated angiotensin I immunoreactive material (AI IM) in both species. 4. The AI IM interfered with the renin assay, but could be completely removed by a cation exchange resin in a batch-wise technique. 5. The enzymatic activity of trypsin-activated prorenin and pre-existing active renin was completely inhibited by a specific inhibitor of renin. 6. The reactions were optimized and an accurate measurement of prorenin in ovarian follicular fluid was developed. 7. The existence of prorenin and renin in bovine ovarian follicular fluid was established. Prorenin and renin in porcine ovarian follicular fluid was demonstrated for the first time. 8. The ratio between ovarian follicular fluid and plasma was 43 for prorenin and 19 for active renin in cattle. The same ratios in pigs were 1.3 and 0.4, respectively. These findings indicate a species difference with respect to the amount of prorenin or active renin present in ovarian follicular fluid.

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“…Oocytes resulting in a live birth display higher follicular prorenin levels than discarded oocytes or empty follicles ( Cornwallis et al , 1990 ). Given that increased theca (-lutein) cell activity associates with successful implantation ( Verberg et al , 2009 ; van Loendersloot et al , 2010 ), it may not be surprising that this is also true for high circulating prorenin levels, since these are the consequence of increased theca cell activity.…”

Section: Discussionmentioning

confidence: 99%

Circulating maternal prorenin and oocyte and preimplantation embryo development: the Rotterdam Periconception Cohort

et al. 2023

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STUDY QUESTION Could circulating maternal prorenin serve as a proxy for oocyte and preimplantation embryo development, assessed by time-lapse parameters and clinical treatment outcomes? SUMMARY ANSWER High circulating maternal prorenin concentrations after ovarian stimulation associate with a larger oocyte area, faster cleavage divisions from the five-cell stage onwards and increased chance of successful implantation. WHAT IS KNOWN ALREADY After ovarian stimulation, circulating prorenin (renin’s precursor), is largely ovary-derived. Prorenin may contribute to ovarian angiotensin synthesis, which is relevant in reproduction given its role in follicular development and oocyte maturation. STUDY DESIGN, SIZE, DURATION Prospective observational cohort study including couples requiring fertility treatment from May 2017 as a subcohort of the ongoing Rotterdam Periconception Cohort conducted in a tertiary referral hospital. PARTICIPANTS/MATERIALS, SETTING, METHODS Between May 2017 and July 2020, 309 couples with an indication for IVF treatment or ICSI were included. Resulting embryos (n = 1024) were submitted to time-lapse embryo culture. Time of fertilization (t0), pronuclear appearance (tPNa), and fading (tPNf) as well as the exact timing of reaching the two- to eight-cell stage (t2–t8), the start of blastulation (tSB), reaching the full (tB), and expanded blastocyst (tEB) were retrospectively recorded. Oocyte area was measured at t0, tPNa, and tPNf. Prorenin was determined at the day of embryo transfer. MAIN RESULTS AND THE ROLE OF CHANCE After adjustment for patient- and treatment-related factors, linear mixed modeling showed that higher prorenin concentrations associate with a larger oocyte area at tPNa (β 64.45 µm2, 95% CI 3.26; 125.64, P = 0.04), and faster progression from five-cell stage onwards (e.g. β8-cell −1.37 h, 95% CI −2.48; −0.26, P = 0.02). Prorenin associated positively with pre-transfer outcomes (e.g. βfertilized oocytes 2.09, 95% CI 1.43; 2.75, P < 0.001) and implantation (odds ratio+β-hCG-test: 1.79, 95% CI 1.06; 3.08, P = 0.03), but not with live birth. LIMITATIONS, REASONS FOR CAUTION This prospective observational study provides associations and therefore residual confounding cannot be excluded and causality has to be shown in intervention studies. WIDER IMPLICATIONS OF THE FINDINGS Theca cell-derived factors, such as prorenin, may help to clarify the underlying endocrine mechanism of oocyte maturation and embryo development, with a special focus on the (patho)physiological reproductive role of prorenin and the identification of factors influencing its secretion and activity, which is of great added value for improving embryo selection and predicting implantation and pregnancy outcomes. This will bring us to investigate which determinants of oocyte quality and embryo development should take center stage in developing preconception care strategies. STUDY FUNDING/COMPETING INTEREST(S) This research was funded by the Department of Obstetrics and Gynecology of the Erasmus MC, University Medical Center, Rotterdam, the Netherlands, and the Erasmus MC Medical Research Advisor Committee’s ‘Health Care Efficiency Research’ program (OZBS72.16080). The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER N/A.

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Follicular fluid renin concentration and IVF outcome

Cited by 16 publications

References 10 publications

Gonadotropin stimulates ovarian renin-angiotensin system in the rabbit.

Gonadotropin stimulates ovarian renin-angiotensin system in the rabbit.

Measurement and Identification of Prorenin and Renin in Ovarian Follicular Fluid From Cattle and Pig

Circulating maternal prorenin and oocyte and preimplantation embryo development: the Rotterdam Periconception Cohort

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