This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by ITSKOVITZ, J. Articles by SEALEY, J. E. Search for Related Content PubMed PubMed Citation Articles by ITSKOVITZ, J. Articles by SEALEY, J. E.

Relationship of Follicular Fluid Prorenin to Oocyte Maturation, Steroid Levels, and Outcome of in Vitro Fertilization^*

Jones Institute for Reproductive Medicine, Department of Obstetrics and Gynecology, Eastern Virginia Medical School (J.I., Z.R., H.C.L.) Norfolk, Virginia 23507
Cardiovascular Center (S.R., J.E.S.) and the Center for Reproductive Medicine and Infertility (Z.R.), Cornell University Medical College New York, New York 10021
The Department of Obstetrics and Gynecology, Rambam Medical Center (J.I.) Haifa 31096, Israel

Address all correspondence and requests for reprints to: Jean E. Sealey, D.Sc, Cardiovascular Center, Cornell University Medical College, 525 East 68th Street, New York, New York 10021.

Address requests for reprints to: Joseph Itskovitz, M.D., D.Sc, Department of Obstetrics and Gynecology, Rambam Medical Center, Haifa 31096, Israel.

Prorenin (PR) is present in high concentrations in the follicular fluid (FF) of the preovulatory follicle. It is the predominant form of renin detected in FF. Its biosynthesis and secretion from the ovary are regulated by gonadotropins. In the present study we measured PR and steroid levels in FF from 136 follicles. Follicular fluids were obtained, 36 h after hCG injection, from 41 ovarian-stimulated patients who underwent follicle puncture and oocyte retrieval for in vitro fertilization. We related FF PR to steroid levels and to the stage of oocyte-cumulus complex maturation. PR levels in 62 FF containing mature healthy fertilized oocytes averaged 2620 ± 157 (±SE) ng/mL·h (728 ± 44 ng/L·s; range, 1020–6880 ng/mL·h, 283–1911 ng/L·s). A subgroup of 16 of these follicles containing mature oocytes were from 7 women who conceived, in which PR levels spanned only the lower range from 1030–2720 ng/mL·h (286–756 ng/L·s). No patient conceived with FF PR above 2800 ng/mL·h (778 ng/L·s), yet one third of all mature follicles were above this range. Lower levels of PR were detected in FF containing immature oocytes (germinal vesicle stage) associated with either compact (1665 ± 480 ng/mL·h; 463 ± 133 ng/L·s; n = 22; P < 0.02) or expanded (1785 ± 193 ng/mL·h; 496 ± 54 ng/L·s; n = 24; P < 0.005) cumulus mass; a subgroup (n = 5) of follicles with immature oocytes and compact cumulus had very high levels of FF PR, ranging from 3830–7520 ng/mL h (1064–2089 ng/L·s), while the remainder had levels less than 1300 ng/mL·h (361 ng/L·s).

Progesterone and estradiol (E₂) were lower in FF surrounding immature oocytes associated with compact (P < 0.005) or expanded (P < 0.02) cumulus, than in those containing mature oocytes. Testosterone (T) and androstenedione were measured in only a fraction of the samples; there were no apparent differences between follicles containing mature and immature oocytes. However, T and androstenedione levels were high in the subgroup of follicles containing immature oocytes and very high levels of PR. Of the hormones measured, T revealed the most striking relationship with PR (r = 0.62; n = 49; P < 0.001). PR in mature follicles disclosed a weak correlation with E₂ and no correlation with progesterone; however, in FF aspirated from women who conceived, a highly significant negative correlation was found between PR and P (r = –0.69; n = 16; P < 0.005), and a positive correlation between PR and E₂ (r = 0.55; n = 16; P < 0.05).

These results suggest that there is a direct relationship between FF PR and the stage of follicular development and oocyte maturation. An intermediate FF PR concentration is associated with mature oocytes that result in pregnancy. Low levels are associated with immature oocytes, while very high levels may be linked to atresia. The direct relationship between FF PR and androgen production is consistent with thecal cells being the source of ovarian PR.

^* This work was supported by NIH Grants HL-40152 and HL-18323SCR.

Received April 17, 1990.

This article has been cited by other articles:

				M. M. Kushnir, T. Naessen, D. Kirilovas, A. Chaika, J. Nosenko, I. Mogilevkina, A. L. Rockwood, K. Carlstrom, and J. Bergquist Steroid Profiles in Ovarian Follicular Fluid from Regularly Menstruating Women and Women after Ovarian Stimulation Clin. Chem., March 1, 2009; 55(3): 519 - 526. [Abstract] [Full Text] [PDF]

				R. Fanchin, D. H. Mendez Lozano, N. Frydman, A. Gougeon, N. di Clemente, R. Frydman, and J. Taieb Anti-Mullerian Hormone Concentrations in the Follicular Fluid of the Preovulatory Follicle Are Predictive of the Implantation Potential of the Ensuing Embryo Obtained by in Vitro Fertilization J. Clin. Endocrinol. Metab., May 1, 2007; 92(5): 1796 - 1802. [Abstract] [Full Text] [PDF]

				A. R. Scialli, A. Lione, J. E. Sealey, J. Itskovitz-Eldor, W. O. Cooper, and W. A. Ray ACE inhibitors and major congenital malformations. N. Engl. J. Med., September 21, 2006; 355(12): 1280 - 1280. [Full Text] [PDF]

				M. Paul, A. Poyan Mehr, and R. Kreutz Physiology of local Renin-Angiotensin systems. Physiol Rev, July 1, 2006; 86(3): 747 - 803. [Abstract] [Full Text] [PDF]

				E. V. Bokal, H. M. Vrtovec, I. V. Klun, and I. Verdenik Prolonged HCG action affects angiogenic substances and improves follicular maturation, oocyte quality and fertilization competence in patients with polycystic ovarian syndrome Hum. Reprod., June 1, 2005; 20(6): 1562 - 1568. [Abstract] [Full Text] [PDF]

				J. F. Reckelhoff and L. A. Fortepiani Novel Mechanisms Responsible for Postmenopausal Hypertension Hypertension, May 1, 2004; 43(5): 918 - 923. [Abstract] [Full Text] [PDF]