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A. PSYCHOYOS

SUMMARY

A new phenothiazine derivative trifluoperazine ('Stelazine') appears to be more effective than chlorpromazine in causing delayed nidation in the rat.

Treatment, started on day 3 of normal pregnancy and repeated every 24 hr., induced delayed nidation in over 80% of the animals treated. This delay was corrected, and implantation brought about, immediately after the exogenous supply of 0·1 μg. of oestradiol.

In a second series of experiments, a single injection of Stelazine was given to females, subsequently spayed and treated with progesterone, and was found to postpone the stage from which ovariectomy is compatible with ovum implantation.

The results obtained support the hypothesis that nidation is induced, under normal conditions, by a release of oestrogen on day 4 of pregnancy. It is suggested that tranquillizers influence ovum implantation by postponing, through the pituitary cycle, this discharge of oestrogen.

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V Rider and A Psychoyos

Abstract

Recent studies suggest that hormonal control of uterine cell proliferation may be moderated by polypeptide growth factors. It remains to be determined, however, whether growth factors cause or are the consequence of hormone action. Basic fibroblast growth factor (bFGF) has been shown to influence cell proliferation and differentiation of a variety of mesoderm-derived cells. To elucidate the regulatory mechanisms controlling stromal cell proliferation and differentiation required for embryo implantation further, immunohistochemical localization of the progesterone receptor and bFGF have been studied. The cell-specific distribution of these proteins was determined in the rat uterus during early pregnancy and after injection of the progesterone receptor antagonist mifepristone (RU 486) at days 1 and 2 post coitum (p.c.) to block implantation. Cell division was restricted to luminal and glandular epithelial cells in pregnant and RU 486-treated rats at day 3 p.c. At day 4 of pregnancy, cell proliferation switched from the epithelia to the stroma in pregnant rats, but after RU 486 treatment division of stromal cells was inhibited significantly (P < 0·05). Progesterone receptor distribution was altered and bFGF was absent in RU 486-blocked stromal cells. Expression of bFGF in luminal and glandular epithelial cells, however, was insensitive to the effects of progesterone receptor antagonism. bFGF content was stimulated in the luminal epithelium and in decidual cells by the implanting embryo. These results indicate that repression of progesterone receptor function in early pregnancy results in a cell-specific loss of bFGF from stromal cells and inhibition of their proliferation. The results further suggest that the regulation of endometrial cell bFGF content is modulated at the site of implantation by the embryo.

Journal of Endocrinology (1994) 140, 239–249

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V. BITTON-CASIMIRI, N. C. RATH and A. PSYCHOYOS

Laboratoire de Physiologie de la Reproduction, CNRS, Hôpital de Bicêtre (INSERM), 94270 Bicêtre, France

(Received 4 January 1977)

Each endometrial population of cells responds differently to ovarian hormones in vivo (Tachi, Tachi & Lindner, 1972; Finn & Porter, 1975). For in-vitro studies on the effects of hormones on individual cell populations, the separation of the luminal epithelium from the stromal tissue presents a major difficulty (Smith, Martin, King & Vertes, 1970; Gerschenson, Berliner & Yang, 1974; Boshier & Katz, 1975; Heald, Govan & O'Grady, 1975). In this report a simple and rapid method for separating the uterine epithelium of the rat is described with details of its use for primary cell culture. Such cultures when carried out in scintillation vials or in depression slides are particularly suitable for studies involving incorporation of radioactive isotopes.

The uterine horns were removed, separated and cleaned free of fat and connective tissues. They were

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D. Martel, R. Frydman, M. Glissant, C. Maggioni, D. Roche and A. Psychoyos

ABSTRACT

The ultrastructure of the luminal surface epithelium was compared in endometrial samples taken from 23 normally cycling women and from 22 patients submitted to ovarian stimulation with clomiphene citrate (100 mg/day for 5 days), human menopausal gonadotrophin (hMG) and human chorionic gonadotrophin (hCG). On day 2 after ovulation, only four out of nine specimens taken from the women in the hormone-treated group were identical to those of normally cycling women. On day 6 after ovulation, only two out of the 13 biopsy specimens from the treated group were the same as those from normally cycling women at that stage. Apical protrusions (pinopodes), typical for this period of the cycle, were missing in 11 of the 13 endometrial samples from the treated group.

These observations suggest that the hormonal treatment applied to induce ovulation (clomiphene citrate, hMG and hCG) can modify the normal development of the prenidatory endometrium, and may thus have a negative effect on the rate of egg implantation.

J. Endocr. (1987) 114, 319–324

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D. Martel, M. N. Monier, D. Roche, V. J. De Feo and A. Psychoyos

ABSTRACT

The main objective of the present study was to analyse the hormonal dependence of the metrial gland formed in pseudopregnant animals following massive decidualization. On day 13 of pseudopregnancy (when the metrial gland reaches its maximal development) animals were ovariectomized and given s.c. implants of oestradiol and/or progesterone. A new implant technique for oestradiol delivery is described which provides circulating concentrations of oestradiol in the physiological range.

In addition, we extended our previous work concerning oestradiol receptor and progesterone receptor concentrations in the metrial gland of pseudopregnant rats. The low oestradiol receptor concentration which we previously reported up to day 17 was maintained until the end of pseudopregnancy (day 21–1·5 fmol/μg DNA), whereas the progesterone receptor concentration remained raised (≃3·5 fmol/μg DNA) from day 13 to day 19 and then decreased on day 21.

The correlation of metrial gland weight and kinetics of the tissue oestradiol and progesterone receptors contents with the circulating oestradiol and progesterone concentrations lead to the following conclusions. First, the maintenance of the metrial gland is strictly progesterone-dependent. It is unlike the deciduoma which regresses spontaneously, even in the presence of progesterone. Secondly, the production of oestradiol receptor, but not of progesterone receptor, appears to be repressed in the metrial gland under the influence of progesterone. Thus, the tissue retains its ability to respond to progesterone because of a high concentration of progesterone receptor. It is difficult to attribute this high tissue progesterone receptor concentration to oestradiol stimulation since, even at low levels, oestradiol induces tissue regression. We suggest that the high progesterone receptor concentration could be due to constitutive (basal) progesterone receptor production.

Journal of Endocrinology (1989) 120, 465–472