Showing posts with label negatively. Show all posts
Showing posts with label negatively. Show all posts

Saturday, April 16, 2011

Serum anti-Mullerian hormone levels are negatively related to Follicular Output RaTe (FORT) in normo-cycling women undergoing controlled ovarian hyperstimulation

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V.K. Genro1,2,3,4, M. Grynberg1,2,3, J.B. Scheffer1,2,3, I. Roux1,2,3, R. Frydman1,2,3 and R. Fanchin1,2,3,*
1Service de Gynécologie-Obstétrique et Médecine de la Reproduction, AP-HP, Hôpital Antoine Béclère, 157, rue de la Porte de Trivaux, Clamart F-92141, France
2Univ Paris-Sud, Clamart F-92140, France
3INSERM, U782, Clamart F-92140, France
4Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Porto Alegre, Brazil *Correspondence address. Tel: +33-1-45-37-40-53; Fax: +33-1-45-37-49-80; E-mail: renato.fanchin{at}abc.ap-hop-paris.frReceived August 25, 2010. Revision received November 9, 2010. Accepted November 24, 2010. BACKGROUND Since in rodents anti-Müllerian hormone (AMH) has been shown to inhibit antral follicle responsiveness to FSH, we aimed at verifying whether a relationship exists between serum AMH levels and antral follicle responsiveness to exogenous FSH in normo-cycling women.

METHODS Serum AMH, estradiol (E2) and FSH levels were prospectively measured on cycle day 3 in patients undergoing controlled ovarian hyperstimulation (COH) with a time-release GnRH agonist and standardized FSH doses. In 162 patients, follicles were counted after pituitary suppression and before FSH administration (baseline; small antral follicles; 3–8 mm), and on the day of hCG (dhCG; pre-ovulatory follicles; 16–22 mm). Antral follicle responsiveness to FSH was estimated by the Follicular Output RaTe (FORT), determined by the ratio pre-ovulatory follicle count on dhCG × 100/small antral follicle count at baseline.

RESULTS Serum AMH levels were positively correlated with the number of small antral follicles at baseline (r = 0.59; P < 0.0001) and pre-ovulatory follicles on dhCG (r = 0.17; P < 0.04). Overall, FORT was 47.5 ± 1.4% and failed to be influenced by the woman's age, BMI or basal E2 and FSH level. Conversely, multiple regression analysis showed that FORT was negatively correlated with AMH levels (r = -0.30; P < 0.001), irrespective of duration of COH and total FSH dose.

CONCLUSIONS The percentage of follicles that effectively respond to FSH by reaching pre-ovulatory maturation is negatively and independently related to serum AMH levels. Although the mechanisms underlying this finding remain unclear, it is in keeping with the hypothesis that AMH inhibits follicle sensitivity to FSH.

© The Author 2010. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (3): 671-677. doi: 10.1093/humrep/deq361 First published online: December 21, 2010

Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.



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Saturday, March 26, 2011

Decidual HtrA3 negatively regulates trophoblast invasion during human placentation

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Harmeet Singh1,*, Yaeta Endo2 and Guiying Nie1
1Prince Henry's Institute of Medical Research, PO Box 5152, 246 Clayton Road, Clayton, VIC 3168, Australia
2Cell-Free Science and Technology Research Center, Ehime University, Matsuyama, Japan *Correspondence address. Fax: +61-3-9594-6125; E-mail: harmeet.singh{at}princehenrys.orgReceived November 17, 2010. Revision received December 23, 2010. Accepted January 12, 2011. BACKGROUND Controlled trophoblast invasion into the maternal decidua (interstitial invasion) is important for placental development. Factors secreted by the maternal decidual cells and the extravillous trophoblast can influence trophoblast invasion and abnormalities in the invasion process may lead to pregnancy complications. Serine protease HtrA3 is highly expressed in the decidual cells in the late secretory phase of the menstrual cycle and throughout pregnancy, and in most trophoblast cell types, apart from the invading interstitial trophoblast during the first trimester. HtrA3 and its family members are down-regulated in a number of cancers and are proposed as tumour suppressors. The current study aimed to investigate whether HtrA3 is secreted by decidual cells, and whether inhibiting such secretion alters trophoblast invasion.

METHODS AND RESULTS Human endometrial stromal cells (HESCs) were decidualized with estradiol, medroxyprogesterone acetate and cyclic adenosine monophosphate. Real-time RT–PCR, western blotting and immunocytochemistry confirmed that HtrA3 mRNA and protein expression increased during decidualization. HtrA3 was also detected in the conditioned media (CM) of the decidualized HESCs, confirming its secretion. For functional studies, a protease-inactive mutant form of HtrA3 which was previously confirmed to be a dominant-negative inhibitor was produced using wheat germ cell-free technology. CM from decidualized HESCs significantly suppressed invasion of trophoblast HTR-8 cells (P < 0.01), whereas inhibition of HtrA3 in this CM by exogenous HtrA3 mutant resulted in increased trophoblast HTR-8 cell invasion (P < 0.001).

CONCLUSIONS These results strongly support the hypothesis that decidual HtrA3 negatively regulates trophoblast invasion.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 748-757. doi: 10.1093/humrep/der019 First published online: February 14, 2011

Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.


 

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