Studies on the Activities of Steroidogenic Enzymes in Corpora Lutea of Early Pregnant Rats Treated With Abortifacient Drugs

Scientific assessment of harmful interactions of chemicals over the entire reproductive cycle are divided into three segments based on the period: from premating and mating to implantation (I), from implantation to major organogenesis (II), and late pregnancy and postnatal development (III). We combined the segments I and II to assessPlathymenia reticulataaqueous extract safety. In order to investigate reproductive toxicity (segment I), pregnant rats received orally 0.5 or 1.0 g/kg of extract, daily, during 18 days. These concentrations were determined by a preliminaryin vitroLD50 test in CHO-k1 cells. A control group received deionized water. The offspring was removed at the 19th day, by caesarean, and a teratology study (segment II) was carried out. The corpora lutea, implants, resorptions, live, and dead fetuses were then counted. Placenta and fetuses were weighted. External and visceral morphology were provided by the fixation of fetuses in Bouin, whereas skeletal analysis was carried out on the diaphanizated ones. The increase in the weights of placenta and fetuses was the only abnormality observed. Since there was no sign of alteration on reproduction parameters at our experimental conditions, we conclude thatP. reticulataaqueous extract is safe at 0.5 to 1.0 g/kg and is not considered teratogenic.

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THE PERSISTENCE OF PROGESTERONE SECRETION IN PREGNANT RATS AFTER HYPOPHYSECTOMY AND HYSTERECTOMY: A COMPARISON WITH PSEUDOPREGNANT, DECIDUOMATABEARING PSEUDOPREGNANT, AND LACTATING RATS

Journal of Endocrinology ◽

10.1677/joe.0.0570063 ◽

1973 ◽

Vol 57 (1) ◽

pp. 63-74 ◽

Cited By ~ 16

Author(s):

I. ROTHCHILD ◽

R. B. BILLIAR ◽

I. T. KLINE ◽

G. PEPE

Keyword(s):

Luteinizing Hormone ◽

Clearance Rate ◽

Progesterone Level ◽

Corpora Lutea ◽

Metabolic Clearance ◽

Metabolic Clearance Rate ◽

Serum Progesterone ◽

Pregnant Rats ◽

Oestrogen Treatment ◽

Progesterone Secretion

SUMMARY To test the hypothesis of Raj & Moudgal (1970) that luteinizing hormone (LH) is the essential luteotrophin during pregnancy in the rat, pregnant rats were hypophysectomized and hysterectomized on either day 12 or day 15 of pregnancy, and the changes in peripheral serum progesterone level measured. The serum progesterone level remained at approximately the day-12 value for 3 days after hypophysectomy and hysterectomy on day 12, but fell drastically and remained low after the same operation on day 15, or in pseudopregnant rats operated on on day 12, or after removal of the ovaries from pregnant rats on day 12. Oestrogen treatment increased the serum progesterone level slightly in the pregnant rats after hypophysectomy and hysterectomy, but not after ovariectomy; it had no effect in the pseudopregnant rats, with or without deciduomata, or in lactating rats nursing litters of seven to nine pups. The corpora lutea stopped growing or slowly regressed soon after hypophysectomy—hysterectomy in all except the pregnant rats operated on on day 12 and treated with oestrogen, and in these growth was very slight. The luteal content of progesterone did not change for 3 days after hypophysectomy—hysterectomy on day 12 of pregnancy, and fell slightly thereafter. The metabolic clearance rate of progesterone was not significantly changed by hypophysectomy—hysterectomy. It thus appears that true secretion of progesterone continues in pregnant rats for about 3 days after day 12 in the absence of the pituitary and placentas, but at a much lower rate than that found in intact, or in day-12 hypophysectomized pregnant rats (Pepe & Rothchild, 1972a). The placental luteotrophin thus seems to increase the rate of progesterone secretion in the absence of LH. The results do not seem to fit with the hypothesis that LH is essential for progesterone secretion.

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Concentrations of cytochrome P450 cholesterol side-chain cleavage enzyme and 3 beta-hydroxysteroid dehydrogenase during prostaglandin F2 alpha-induced luteal regression in cattle

Reproduction Fertility and Development ◽

10.1071/rd9951213 ◽

1995 ◽

Vol 7 (5) ◽

pp. 1213 ◽

Cited By ~ 10

Author(s):

RJ Rodgers ◽

CA Vella ◽

FM Young ◽

XC Tian ◽

JE Fortune

Keyword(s):

Cytochrome P450 ◽

Hydroxysteroid Dehydrogenase ◽

Side Chain ◽

Corpora Lutea ◽

Steroidogenic Enzymes ◽

Rapid Reduction ◽

Plasma Progesterone ◽

Side Chain Cleavage ◽

Prostaglandin F2 Alpha ◽

Chain Cleavage

Prostaglandin F2 alpha (PGF2 alpha)-induced regression of the corpus luteum causes both plasma progesterone concentrations and luteal concentrations of mRNA encoding the steroidogenic enzyme 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) to fall in parallel. To investigate the hypothesis that a decline in the concentrations of mRNA encoding steroidogenic enzymes causes plasma progesterone to fall, the luteal concentrations of the enzymes 3 beta-HSD and cytochrome P450 cholesterol side-chain cleavage were measured during induced luteolysis. Holstein heifers were treated with PGF2 alpha (25 mg Lutalyse) on Day 6 or Day 7 of the oestrous cycle and corpora lutea were collected 0 h, 2 h, 12 h, and 24 h later (n = 6, 4, 4, and 4 respectively). Analyses of the steroidogenic enzymes were carried out by Western immunoblotting. The luteal concentrations of both steroidogenic enzymes did not decrease over the 24-h period. It is concluded that, although the concentrations of mRNA encoding steroidogenic enzymes may decline in response to PGF2 alpha, this does not lead to a sufficiently rapid reduction in the concentrations of the enzymes to precede, and thus cause, the decline in plasma progesterone concentrations. Thus, the mechanism for the initial decline in plasma progesterone concentrations during luteolysis is still not known.

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OESTROGEN BIOSYNTHESIS BY THE RAT OVARY IN EARLY PREGNANCY

Acta Endocrinologica ◽

10.1530/acta.0.0690127 ◽

1972 ◽

Vol 69 (1) ◽

pp. 127-140 ◽

Cited By ~ 7

Author(s):

A. Zmigrod ◽

H. R. Lindner

Keyword(s):

Early Pregnancy ◽

Side Chain ◽

Interstitial Tissue ◽

Corpora Lutea ◽

Microsomal Preparation ◽

Pregnant Rats ◽

Side Chain Cleavage ◽

Chain Cleavage ◽

Rat Ovary

ABSTRACT Ovarian homogenates or microsomes from pregnant rats were capable of aromatizing C19-steroids (testosterone or androstenedione) in the presence of NADPH to form oestrone and 17β-oestradiol; the microsomal preparation was also capable of forming these oestrogens from progesterone. The rate of oestrogen formation from either type of substrate increased during the first week of pregnancy. Aromatizing activity reached a plateau by about the fifth to sixth day after mating, at a level similar to that found in the ovaries of pro-oestrous rats. Side-chain cleaving activity continued to rise until the seventh day of pregnancy, yet remained far below that in pro-oestrous animals. Hence side-chain cleavage, rather than aromatizing activity, must limit oestrogen formation during early pregnancy. Isolated corpora lutea of pregnancy and the remainder of the ovary, consisting of involuting corpora lutea, small follicles and interstitial tissue, contributed about equally to ovarian oestrogen production from progesterone under the in vitro conditions. Neither aromatizing nor side-chain splitting activity showed a distinct peak on the fourth day of pregnancy, the time of the putative prenidatory oestrogen surge.

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PROSTAGLANDIN E2: ANALYSIS OF EFFECTS ON PREGNANCY AND CORPUS LUTEUM IN HAMSTERS AND RATS

Acta Endocrinologica ◽

10.1530/acta.0.071s003 ◽

1972 ◽

Vol 71 (3_Suppl) ◽

pp. S3-S32 ◽

Cited By ~ 3

Author(s):

A. P. Labhsetwar

Keyword(s):

Combined Treatment ◽

Corpora Lutea ◽

Pregnant Rats ◽

Plasma Progesterone ◽

Implantation Sites ◽

Near Term ◽

Exogenous Progesterone ◽

Blue Reaction ◽

Egg Transport ◽

Reproductive Processes

ABSTRACT Effects of prostaglandin (PG) E2 on some reproductive processes of hamsters and rats were studied. The PG exerted antifertility effects in either species although it was 4–10 times less potent than PGF2α. Antifertility doses of PGE2 caused morphological degeneration of corpora lutea, induced fresh ovulations during the course of the treatment, significantly decreased peripheral progesterone levels and inhibited development of deciduomata in response to trauma. Both pregnancy and decidual growth could be maintained by simultaneous administration of exogenous progesterone. PGE2 also decreased plasma progesterone concentration in pseudopregnant-hysterectomized hamsters although the decrease was not significant when compared with intact pregnant or pseudopregnant hamsters. PGE2 produced no demonstrable effects on egg transport in hamsters but may have induced delayed implantation in rats by causing tubal retention of zygotes. The antifertility doses of PGE2 but not of PGF2α inhibited implantation of a proportion of blastocysts as studied by the Pontamine blue reaction and adversely affected the spacing mechanism of blastocysts in the uterus significantly reducing the distance between the adjacent implantation sites. When PGs E2 and F2α were given together to pregnant rats in doses which were virtually ineffective individually, the combined treatment caused loss of pregnancy. Administration of PGE2 to near term hamsters produced premature littering but oxytocin in doses tried proved inactive. Antifertility doses of PGE2 produced diarrhoea in rats but not in hamsters. The results demonstrate that PGE2 shares the luteolytic property of PGF2α but in addition possesses several other properties not known to be shared by PGF2α.

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Evaluation of the Developmental Toxicity of α-Methyl-3,4-Methylene-Dioxyhydrocinnamic Aldehyde in Rats

International Journal of Toxicology ◽

10.1080/10915810600609312 ◽

2006 ◽

Vol 25 (2) ◽

pp. 127-132 ◽

Cited By ~ 2

Author(s):

Anne Marie Api ◽

Elise M. Lewis ◽

Alan M. Hoberman ◽

Mildred S. Christian ◽

Robert M. Diener

Keyword(s):

Corn Oil ◽

Developmental Toxicity ◽

Clinical Signs ◽

Feed Consumption ◽

Corpora Lutea ◽

Sprague Dawley ◽

Pregnant Rats ◽

Excessive Salivation ◽

Sprague Dawley Rats ◽

Body Weights

The developmental toxicity of α-methyl-3,4-methylene-dioxyhydrocinnamic aldehyde (MMDHCA), a widely used fragrance ingredient, was evaluated for developmental toxicity in Sprague-Dawley rats (25/group; cesarean-sectioning identified 21 to 25 pregnant rats/group). Oral dosages of 0 (corn oil), 62, 125, or 250 mg/kg/day were administered by gavage on days 7 through 17 of gestation (GDs 7 through 17). Rats were observed for viability, clinical signs, body weights, and feed consumption. Necropsy and cesarean sectioning occurred on GD 21. Uteri were examined for number and distribution of implantations, live and dead fetuses, and early and late resorptions. Numbers of corpora lutea were also recorded. Fetuses were weighed and examined for gender, gross external changes, and soft tissue or skeletal alterations. Analysis of dosage preparations verified calculated dosages ±10%. No deaths occurred. Excessive salivation occurred in all groups, but the incidence was increased at 250 mg/kg/day. The 250 mg/kg/day dosage also was associated with a significant increase in the incidences of a clear, red or yellow perioral and/or red perivaginal substance and significant reductions in mean feed consumption and body weight gains (11.6% and 7.4%, respectively) during the entire dosage period. No gross changes attributable to MMDHCA were observed at necropsy. Cesarean section or litter parameters, as well as fetal alterations, were not affected by MMDHCA at 250 mg/kg/day or either of the lower dosages tested. Based on these data, maternal and developmental no-observable-effect levels (NOAELs) of 125 and >250 mg/kg/day, respectively, were established for MMDHCA. It is concluded that MMDHCA is not a developmental toxicant in rats under the conditions of this study and dosing regimen.

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