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Biomedical subjects

A Tenhunen

Publications and source records attributed to A Tenhunen.

At least 19 recordsLinked to original sources
PubMed2000

BMP-4 affects the differentiation of metanephric mesenchyme and reveals an early anterior-posterior axis of the embryonic kidney.

Bone morphogenetic protein-4 (BMP4), a member of the transforming growth factor-beta (TGF-beta) family, regulates several developmental processes during animal development. We have now studied the effects of BMP-4 in the metanephric kidney differentiation by using organ culture technique. Human recombinant BMP-4 diminishes the number of ureteric branches and changes the branching pattern. Our data suggest that BMP-4 affects the ureteric branching indirectly via interfering with the differentiation of the nephrogenic mesenchyme. The clear positional preference of the defects to posterior mesenchyme might reflect an early anterior-posterior patterning of the metanephric mesenchyme. The smooth muscle alpha-actin expressing cell population around the ureteric stalk, highly expressing Bmp-4 mRNA, is also expanded in kidneys treated with BMP-4. Thus, BMP-4 may be a physiological regulator of the development of the periureteric smooth muscle layer and ureteric elongation.

Animals↗
PubMed1998

Overexpression of VEGF in testis and epididymis causes infertility in transgenic mice: evidence for nonendothelial targets for VEGF.

Vascular endothelial growth factor (VEGF) is a key regulator of endothelial growth and permeability. However, VEGF may also target nonendothelial cells, as VEGF receptors and responsiveness have been detected for example in monocytes, and high concentrations of VEGF have been reported in human semen. In this work we present evidence that overexpression of VEGF in the testis and epididymis of transgenic mice under the mouse mammary tumor virus (MMTV) LTR promoter causes infertility. The testes of the transgenic mice exhibited spermatogenic arrest and increased capillary density. The ductus epididymidis was dilated, containing areas of epithelial hyperplasia. The number of subepithelial capillaries in the epididymis was also increased and these vessels were highly permeable as judged by the detection of extravasated fibrinogen products. Intriguingly, the expression of VEGF receptor-1 (VEGFR-1) was detected in certain spermatogenic cells in addition to vascular endothelium, and both VEGFR-1 and VEGFR-2 were also found in the Leydig cells of the testis. The infertility of the MMTV-VEGF male mice could thus result from VEGF acting on both endothelial and nonendothelial cells of the male genital tract. Taken together, these findings suggest that the VEGF transgene has nonendothelial target cells in the testis and that VEGF may regulate male fertility.

Animals↗
PubMed1996

Balanced analgesia improves recovery and outcome after outpatient tubal ligation.

Outpatient surgery benefits patients only if postoperative sequelae are effectively treated. After laparoscopic tubal ligation (TL) intense pain and consequent postoperative nausea and vomiting (PONV) has been a problem delaying recovery and resulting in hospital admission. Ninety patients were randomised to this double-blind study, the aim being to evaluate the effect of balanced analgesia on postoperative pain and recovery after sterilization. The balanced analgesia group received 5 ml of 2% lidocaine gel on the sterilization clips and perioperatively 200 mg of ketoprofen i.v. The lidocaine group received 5 ml of 2% lidocaine gel on the clips and placebo i.v. perioperatively. The placebo group received 5 ml of placebo gel on the clips and placebo i.v. perioperatively. Infusion of propofol and 67% nitrous oxide in oxygen were used for maintenance of anesthesia. Succinylcholine and vecuronium were used for muscle relaxation and 0.1 mg of fentanyl i.v. was given to all patients at induction of anesthesia. Postoperative pain and analgesic requirements, incidence of PONV and need for antiemetic medication were all significantly lower in the balanced analgesia group. Home readiness was consistently achieved 70-90 min sooner in the balanced analgesia group compared to the other groups (P < 0.01 between the balanced analgesia and the placebo group), and the patients were able to return to normal activity sooner (cumulatively 93% of the patients in the balanced analgesia group vs. 60% in the other two groups (P < 0.01 between the balanced analgesia and the other groups) had returned to normal activity on the 2nd postoperative day). It is concluded that in patients undergoing laparoscopic TL the combination of analgesic regimens with different mechanisms of action offer a simple and efficient way of postoperative pain relief, as well as an improvement of quality (i.e. less PONV) and speed of recovery.

Adult↗
PubMed1993

Ovarian electrocauterization causes LH-regulated but not insulin-regulated endocrine changes.

OBJECTIVE: We studied the effects of ovarian electrocauterization on the serum levels of luteinizing hormone (LH), testosterone, insulin, sex hormone-binding globulin (SHBG) and insulin-like growth factor binding globulin-1 (IGFBP-1) in women with polycystic ovarian disease (PCOD). DESIGN: Prospective. PATIENTS: Ten women with PCOD admitted to a University Infertility Clinic. MEASUREMENTS: Fasting blood samples for determination of hormone levels were taken during the follicular phase before and one month after laparoscopic ovarian electrocauterization. RESULTS: One month after electrocauterization the serum mean +/- SE LH levels had decreased from 14.4 +/- 1.9 to 10.9 +/- 1.1 U/l (P < 0.05), while the serum insulin levels showed no significant change (10.3 +/- 2.0 and 8.1 +/- 1.3 mU/l). The levels of IGFBP-1 (33.9 +/- 8.2 and 38.4 +/- 13.7 micrograms/l) and SHBG (48 +/- 10.4 and 43 +/- 5.7 nmol/l) showed no significant changes. Testosterone decreased from 3.9 +/- 2.6 to 2.9 +/- 0.3 nmol/l (P < 0.001) and androstenedione from 15.0 +/- 1.2 to 12.0 +/- 1.5 nmol/l (P = 0.05). After electrocautery seven out of ten PCOD patients ovulated either spontaneously (n = 3) or with clomiphene citrate (n = 4), and two of them conceived. CONCLUSIONS: Ovarian electrocautery leads to resumption of ovulatory cycles in some but not all PCOD patients. This effect seems to be mediated by reduction of serum LH and androgen levels, while the insulin-driven pathway via SHBG and IGFBP-1 remains unaffected.

Adult↗
PubMed1992

Expectant management of ectopic pregnancy.

OBJECTIVE: To evaluate expectant management in selected cases of ectopic pregnancy. METHODS: Transvaginal sonography and estimation of serum hCG concentrations were used in the evaluation and follow-up of ectopic pregnancy. Entry criteria for expectant management were: decreasing level of serum hCG, diameter of the ectopic pregnancy less than 4 cm, and no signs of rupture or acute bleeding by vaginal sonography. RESULTS: Expectant management was studied in 83 patients, representing 26% of all ectopic pregnancies during a 2-year period. In 57 patients (69%), spontaneous resolution occurred, corresponding to 18% of all ectopic pregnancies. Laparoscopy was performed in 26 because of clinical symptoms or a rise in hCG level after expectant management for 1-18 days. One patient had a tubal rupture requiring tubal resection by laparoscopy. No serious complications occurred. With increasing experience, the rate of expectant management and spontaneous resolution increased during study period. CONCLUSION: Expectant management with repeated vaginal sonography and estimations of serum hCG concentrations is a useful form of treatment for ectopic pregnancy in selected cases.

Chorionic Gonadotropin↗
PubMed1991

Conservative treatment of ectopic pregnancy.

As a conservative nonsurgical treatment of an early ectopic pregnancy, local prostaglandin, parenteral or local methotrexate, local hyperosmolar glucose, and also expectant management have been used successfully in selected cases. The success rate of conservative treatment has been 71%-100% and that of tubal patency after different kinds of conservative treatment 72-93% of patients. In the present study of expectant management in early ectopic pregnancy in patients with decreasing serum hCG levels, spontaneous resolution was observed in 64.6% of patients and in the total series of 207 ectopic pregnancies in 15.0% of patients. Expectant management of early ectopic pregnancy is recommended when emergency surgery is not needed on admission and the serum hCG level is decreasing as noted in two consecutive estimations with an interval of 1-2 days.

Adnexa Uteri↗
PubMed1987

Low LH receptor content in corpora lutea in luteinized unruptured follicle (LUF) syndrome.

Concentrations of LH receptors in ovarian corpora lutea were measured in four women with ultrasonically monitored cycles, [in which luteinized unruptured follicles (LUF) were observed] and in one woman with an LUF observed during laparotomy. LH receptor concentrations were also measured in four control patients with proven fertility. The LH receptor concentrations in cases of LUF syndrome were on average 60% lower (P less than 0.01) than in the control patients. These results suggest that in LUF patients there is a disorder in the mechanism of LH action in the developing follicles.

Adult↗
PubMed1986

In vitro recovery of human chorionic gonadotropin-stimulated cyclic adenosine 3',5'-monophosphate production in desensitized human granulosa-luteal cells.

Human granulosa-luteal cell production of cyclic adenosine 3',5'-monophosphate (cAMP) and progesterone (P) were studied in response to purified human chorionic gonadotropin (hCG) in cultured cells from hyperstimulated follicles of in vitro fertilized patients. The hCG injection given to the patients 36 hours before laparoscopy caused partial desensitization of adenylate cyclase of these cells to gonadotropins. Preincubation of the cells in hormone free medium for 2 to 3 days significantly increased their cAMP responsiveness to hCG. P production was stimulated initially by hCG and showed no desensitization. In the cells preincubated for 72 hours without hCG, a subsequent stimulus of 50 ng/ml of hCG elicited maximal cAMP response, whereas 1 ng/ml of hCG was sufficient to bring about maximal P secretion. Time-course studies indicated that maximal cAMP response to hCG was obtained in 1 to 3 hours. Both basal and hCG-stimulated P accumulation continued to rise for up to 24 hours. Preincubation of granulosa-luteal cells from hyperstimulated follicles improves the cells' cAMP responsiveness to hCG, whereas P response remains unaltered.

Chorionic Gonadotropin↗
PubMed1985

Pregnancy proteins in seminal plasma, seminal vesicles, preovulatory follicular fluid, and ovary.

A number of proteins previously thought to be specific for the placenta or pregnancy have been identified in the fluids bathing both the oocyte and the sperm. In many cases their concentrations in follicular fluid and seminal plasma greatly exceeded those in the serum of nonpregnant women or men, and sometimes they even exceeded the levels in pregnancy sera. We report here the occurrence of PP5, PP12, PP14 and PAPP-A in follicular fluid and seminal plasma. In follicular fluid, the levels of PP5, PP12, and PAPP-A correlate with the estrogen concentration of the same fluid, and the PP12 and PAPP-A levels also bear a positive correlation to the progesterone concentration. The levels of PP12 and PAPP-A increase as the follicle grows, as do the levels of many steroid hormones. Therefore, the apparent correlations observed may be merely coincidental. However, circumstantial evidence from other reproductive organs indicates that the synthesis of PP12 and PAPP-A is stimulated by progesterone. Results of immunohistochemical staining show that PP12 and PAPP-A are localized in the luteinized granulosa cells and the corpus luteum. Previous studies indicate that PP5 and PAPP-A inhibit the action of proteolytic enzymes plasmin and elastase, which are believed to be involved in the mechanisms of ovulation. The study of the significance of these various placental proteins for human reproduction is only at its beginning. Clearly, elucidation of their function is the key to a more fundamental understanding of their role in the events governing ovulation and implantation.

Adult↗
PubMed1985

Pregnancy proteins in the endometrium after follicle aspiration for in vitro fertilization.

Placental proteins PP10, PP12, and PP14 and pregnancy-associated plasma protein A (PAPP-A) and relaxin (RX) were studied by the immunoperoxidase method in the uterine mucosa at the time of embryo replacement in 18 women for whom no embryo was available to be replaced. All subjects had received 17 alpha-hydroxyprogesterone caproate at the time of follicle aspiration, which had been performed 36 hours after preovulatory administration of hCG. The time between follicle aspiration and endometrial biopsy varied from 26 to 216 hours. PP10 was not detected in any specimen. RX was found in 17 of 18, PP12 in 15 of 18, PAPP-A in 14 of 18, and PP14 in 6 of 18 specimens. In a normal cycle, PP12, PAPP-A and RX appear in the endometrium on the fourth day post ovulation. In the conditions described above the same proteins could be seen in the endometrium sooner after oocyte retrieval. This may be due to a strong progesterone effect after multiple follicle aspirations and treatment with 17 alpha-hydroxyprogesterone. The significance of the occurrence of these pregnancy proteins as well as that of the morphologic and biochemical maturity of the endometrium at the time of embryo transfer are discussed.

Endometrium↗
PubMed1984

The occurrence of relaxin in hyperstimulated human preovulatory follicles collected in an in vitro fertilization program.

The avidin-biotin immunoperoxidase method and antisera against highly purified porcine relaxin were utilized to localize relaxin-like immunoreactivity in biopsied specimens from six preovulatory follicles from four women undergoing laparoscopy for oocyte retrieval in an in vitro fertilization program. By histological criteria, three of the follicles were luteinized and three were not. Relaxin was found in the granulosa cells of those cells which showed histological luteinization, whereas no relaxin was found in the nonluteinized preovulatory follicles. Our results show, for the first time, the occurrence of relaxin in the human ovary before ovulation and they suggest that the appearance of relaxin is related to the luteinization process.

Chorionic Gonadotropin↗
PubMed1984

The in vitro fertilization program in Helsinki.

In the in vitro fertilization program at Departments I and II of Gynecology and Obstetrics, University of Helsinki, 57 patients were stimulated with clomiphene and hMG. Follicular growth was monitored by ultrasound and serum estradiol measurements. Laparoscopic follicular puncture was performed 36h after hCG injection. Three hundred seventy-five follicles were punctured and 227 oocytes recovered, representing an oocyte recovery rate of 61%. A total of 130 oocytes (57%) showed evidence of fertilization and 71% of the fertilized oocytes cleaved. Fifty-seven embryo transfers were carried out at the two- to eight-cell stage. Multiple embryos were transferred to 24 patients. Biochemical pregnancies were encountered in two cases; early abortions, 3-5 weeks after implantation, in two cases. One normal ongoing single pregnancy occurred from a transfer of three four-cell embryos.

Adult↗
PubMed1984

Diagnosis of luteinized unruptured follicle (LUF) syndrome by ultrasound.

To evaluate the role of ultrasound in diagnosing luteinized unruptured follicle (LUF), 37 women with unexplained infertility were examined for two to three menstrual cycles. Laparoscopy or laparotomy was performed on days 16 to 18 of the third study cycle in 25 patients. The LUF syndrome was suspected at ultrasound examination in 57 of 100 cycles observed. In the remaining 43 cycles, follicular collapse was observed in 33, and 10 were diagnosed as anovulatory. At laparoscopy or laparotomy on 25 patients, 18 of the 21 patients diagnosed as having LUF by ultrasound had a corpus luteum without a stigma. The other three cases diagnosed as LUF by ultrasound had ovulation stigmata. Additional findings in the 25 patients who underwent laparotomy or laparoscopy were endometriosis in 7 (5 of whom had LUF as well), ovulation in 5, bilateral hydrosalpinx in 1, and inability to visualize the ovaries because of adhesions in 1. The LUF syndrome was not a consistent change in the ovulatory pattern of most of the patients. It occurred by ultrasound diagnosis in three consecutive cycles in only 34% of patients.

Adult↗
PubMed1984

Follicular fluid prostaglandins in endometriosis and ovarian hyperstimulation.

To study the presence of prostaglandin F2 alpha (PGF2 alpha), prostacyclin (PGI2), and thromboxane A2 (TxA2) in the human ovary, follicular fluid samples were collected with puncture at laparoscopy in 17 women with pelvic endometriosis, 17 women with tubal occlusion and healthy ovaries, and 5 women with tubal occlusion and induced ovarian hyperstimulation between menstrual cycle days 8 and 18. The concentrations of the metabolites of PGF2 alpha, PGI2, and TxA2, i.e., 13,14-dihydro-15-keto PGF2 alpha (M-PGF2 alpha), 6-keto PGF1 alpha, and TxB2, respectively, were measured with radioimmunoassays. Each prostanoid was detected in follicular fluid, but their concentrations were unrelated to the menstrual cycle day at collection. Moreover, these concentrations were similar in various groups of patients. The data suggest that the human ovary produces PGF2 alpha, PGI2, and TxA2 in vivo and that these prostanoids, as measured from follicular fluid, may not be of primary significance in ovulation or endometriosis.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Hyperstimulated human preovulatory follicular fluid, luteinized cells of unruptured follicles, and corpus luteum contain pregnancy-associated plasma protein A (PAPP-A).

Radioimmunoassay, gel filtration, and immunoperoxidase methods were used to study the occurrence, properties, and concentration of pregnancy-associated plasma protein A (PAPP-A) in the human ovary and in the follicular fluid from 97 hyperstimulated follicles from 29 infertile women participating in an in vitro fertilization program. At the detection level of 15 micrograms/l, PAPP-A was found in 83 of 97 follicular fluids, the levels ranging from undetectable to 483 micrograms/l (median, 130 micrograms/l). In gel filtration, PAPP-A immunoreactivity of follicular fluid eluted in the same volume as placental PAPP-A, and the dose-response curves of follicular fluid PAPP-A and purified PAPP-A were parallel. The PAPP-A concentration was not affected by prior treatment with a protease inhibitor. Follicular fluid aspirates containing the ovum had a higher PAPP-A concentration than those in which no ovum was detected (P less than 0.01), whereas no difference was found in the PAPP-A concentrations between follicles yielding an ovum which was fertilized and cleaved and those yielding an unfertilizable oocyte. There was a correlation between PAPP-A and estradiol or progesterone concentrations, and between the PAPP-A concentration and the volume of follicular fluid aspirate. In hyperstimulated unruptured follicles, PAPP-A was localized in the luteinized granulosa and theca interna cells, but not if luteinization was not observed. Corpus luteum cells were also PAPP-A positive, whereas unstimulated Graafian follicles were negative. Our results indicate that PAPP-A appears in the hyperstimulated follicle shortly before ovulation and may thus play a part in the early events of human reproduction.

Chromatography, Gel↗
PubMed1984

Human preovulatory follicular fluid, luteinized cells of hyperstimulated preovulatory follicles, and corpus luteum contain placental protein 12.

RIA gel filtration, isoelectric focusing; and immunoperoxidase staining were employed to study the occurrence and physicochemical characteristics of placental protein 12 (PP12) in the human ovary, corpus luteum, and preovulatory follicular fluid. Fluid aspirated from 75 follicles from 22 women hyperstimulated for in vitro fertilization contained 6-230 micrograms/liter PP12-like immunoreactive material. The dose-response curves of follicular fluid PP12, amniotic fluid PP12, and purified human placental PP12 were parallel in the PP12 RIA. In gel filtration, follicular fluid PP12 eluted in the same volume as purified PP12. The isoelectric point of follicular fluid PP12 was 4.9 and that of purified placental PP12 4.6-4.7. A positive correlation was found between follicular fluid estradiol and PP12, progesterone and PP12, and follicular fluid volume and PP12 concentrations. By immunoperoxidase staining, PP12 was not detectable in unstimulated ovarian tissue before ovulation. In hyperstimulated preovulatory follicles biopsied in connection with follicle aspiration, PP12 was found in the granulosa cells which were luteinized (n = 3), whereas in those hyperstimulated follicles (n = 5) with no luteinization, no PP12 was found either. PP12 was seen in all corpora lutea (n = 5) from unstimulated menstrual cycles. These results show that the occurrence of PP12 is not limited to the placenta. The correlation between follicular fluid steroid and PP12 levels and the findings by immunoperoxidase staining suggest that PP12 is related to endocrine phenomena of the ovary, possibly to the luteinization process.

Chromatography, Gel↗