Utero-ovarian relationships in placental mammals: role of uterus and embryo in the regulation of progesterone secretion by the corpus luteum. A review.

The role of the uterus and that of the embryo in regulating luteal progesterone secretion appear to differ greatly, depending on the mammal. However, the situation is analogous in some mammals. The main role of luteal progesterone is to permit the establishment and maintenance of pregnancy, and there appears to be a relationship between the type of placenta and the uterine and embryonic modes of regulating luteal activity. When placentation is endotheliochorial (carnivores), the corpus luteum is active over a remarkably long period; the uterus does not have any limiting action in any of the species studied and the presence of an embryo does not profoundly modify luteal progesterone secretion. When placentation is epitheliochorial (artiodactyls), hysterectomy, like the presence of an embryo in the uterus, considerably prolongs luteal activity in all the species studied. The uterus limits the duration of progesterone secretion by producing luteolytic PGF2 alpha. The embryo maintains progesterone secretion by acting directly on the uterus, causing a change in the synthesis of prostaglandins; this change eventually favors the synthesis of luteotropic PGE's. Moreover, the embryo secretes LH-like and possibly prolactin-like luteotropic factors. When placentation is hemochorial (rodents, lagomorphs, higher primates), the uterus plays a slight role or none at all in regulating luteal activity in all the species studied. The presence of an embryo prolongs and often increases progesterone secretion. The embryo acts in two ways: (a) by causing decidual tissue to form in the endometrium; this tissue secretes the luteotropic factors, uterine "prolactin" and sometimes PGE, and (b) by secreting an LH-like chorionic hormone that is produced in large quantities in primates.

[Putative causes of the frequency of extra-uterine pregnancy in women and its rarity in domestic mammals]. / Causes possibles de la frequency des gestations extra-uterines chez la femme et de leur rarete chez les mammiferes domestiques.

PIP: This article examines possible factors that would explain the frequency of extrauterine pregnancies in women and their rarity in domestic mammals. About 1% of pregnancies are extrauterine, and of these about 98% are tubal, a condition almost unknown among other mammals. Ectopic pregnancy increases in women with age and parity, but among domestic mammals the rotation of females used for reproduction is usually rapid. Women undergoing surgical interventions for tubal pathology due to congenital conditions, infections, or other causes have a high rate of ectopic pregnancy, but mammals with tubal pathology generally do not reproduce. Ectopic pregnancies are not seen in domestic animals subjected to experimental tubal surgery. In women but not in mammals the administration of gonadotropins to promote ovulation is associated with a higher rate of ectopic pregnancy. The failure of some types of contraceptives, such as tubal sterilization, is associated with ectopic pregnancy in women but no comparable situation is found in domestic animals. It is likely that the mechanisms of reproduction in mammals, unlike those in women, inhibit the development of ectopic pregnancies. Several factors have been identified which distinguish women and domestic mammals: in women the presence of the embryo is not required in the uterus for luteal progesterone secretion to take place, the embryo is capable of surviving in either the tubes or the uterus, the placenta is hemochorial, and implantation is interstitial. The 4 features have not been found together in any other mammal, and it appears that the more numerous the differences in any mammal, the smaller the chances that a tubal pregnancy will occur. 2 approaches to study of the differences in humans and mammals are recommended: use of an experimental model more similar to the human, and use of the usual experimental species to analyze the relative importance of each of the factors identified.^ieng

Ovulation.

Three events lead to the ovulation of a normal oocyte: cytological and biochemical changes in the follicle wall, disintegration of the follicle apex and oocyte maturation. The remodelling of the follicle wall results from plasmin and collagenase activities. The thinning of the follicular apex, in addition to these enzymes, involves hydrolases liberated by dying ovarian epithelial cells. PGF2 alpha and histamine are also involved but it is not known precisely how they contribute to the apical dissociation. The nuclear and cytoplasmic maturation of the oocyte is highly dependent on the synthetic activities of granulosa cells which are regulated by LH and FSH. The pulsatile secretion of these gonadotrophins is not necessary for the final phase of Graafian follicle growth and rupture. Why high levels of gonadotrophins, normally reached during the preovulatory surge, completely change the structure and the biochemical activities of all follicular compartments remains unknown and in fact has never been studied. Moreover, there is very little information concerning the mechanisms involved both in the increase of blood flow during the LH surge and later in the blood stasis at the follicular apex. Steroids, whatever their levels and ratio, are of little if any concern in follicle rupture and nuclear maturation. However, their importance has been clearly demonstrated in the cytoplasmic maturation of the oocyte of some species.

Resumption of oestrous behaviour and cyclic ovarian activity in suckling and non-suckling ewes.

In Préalpes de Sud ewes after an autumn lambing, the mean post-partum interval to first LH surge was 10 +/- 1 days and 17 +/- 1 days for non-suckling and suckling ewes, respectively. Post-partum interval to first luteal phase, estimated from plasma progesterone concentrations, was similar in non-suckling and suckling ewes (27 +/- 1 days and 28 +/- 5 days, respectively). Interval to first oestrus was shorter in non-suckling (22 +/- 2 days) than in suckling ewes (35 +/- 2 days) but these first oestrous periods were followed by short luteal phases in 60% (12/20) of non-suckling ewes and in only 7% (2/29) of suckling ewes. Finally, suckling slightly postponed the resumption of the first oestrus followed by a normal oestrous cycle (37 +/- 1 days versus 31 +/- 2 days) because progesterone, essential for oestrus expression, was secreted mainly during normal luteal phases in 70% (21/30) of suckling ewes and during short cycles in 95% (21/22) of non-suckling ewes. Therefore, the primary consequence of suckling is to regulate the conditions of resumption of cyclic ovarian activity after parturition.

Resumption of gonadotrophin release during the post-partum period in suckling and non-suckling ewes.

The post-partum secretion of LH, FSH and prolactin was monitored in 15 suckling and 6 non-suckling Préalpes du Sud ewes lambing during the breeding season by measuring plasma hormone concentrations daily at 6-h intervals and also weekly at 20-min intervals for 6 h from parturition to resumption of regular cyclic ovarian activity. There was a constant phenomenon in the resumption of normal patterns of FSH and LH secretion: there was a rise in FSH values culminating on average on Day 4 post partum and returning subsequently to values observed during the oestrous cycle, and concurrently an increase in the frequency and amplitude of LH pulses more progressive in suckling than in non-suckling ewes which led to an elevation of LH mean concentrations and occurrence of an LH surge. Since neither the FSH secretory pattern nor FSH mean values differed between suckling and non-suckling ewes, the results suggested that LH pulsatile pattern was a major limiting factor for the resumption of normal oestrous cycles. Before regular oestrous cycles resumed other changes in preovulatory LH surges also occurred: (i) they increased in duration and probably in amplitude; (ii) they were preceded by an acceleration in LH pulse frequency and a large decrease in FSH values as in normal cyclic ewes; and (iii) at least in non-suckling ewes they occurred concurrently with a prolactin surge.

Interactions between 17 beta-estradiol and the hypothalamo-pituitary beta-endorphin system in the regulation of the cyclic LH secretion.

This paper further substantiates the physiological role of beta-endorphin (beta-END) in the control of the cyclic LH secretion and provides new data on the interactions between 17 beta-estradiol (17 beta-E2) and beta-END at both the hypothalamic and pituitary levels. At the hypothalamic level, during the estrous cycle in rats, beta-END concentrations were highest on diestrus I in the arcuate nucleus, median preoptic area and median eminence and lowest at the time of the preovulatory 17 beta-E2 surge on proestrus, before the subsequent preovulatory hypothalamic GnRH and plasma LH surges. Data obtained in ovariectomized 17 beta-E2-treated ewes support the direct involvement of 17 beta-E2 in changes in beta-END and GnRH concentrations in these hypothalamic areas. At the anterior pituitary level, in vitro results obtained using anterior pituitaries from the proestrus morning cycling female rat have shown that 17 beta-E2 strongly suppresses beta-END secretion and that GnRH stimulates the release of beta-END. Furthermore, marked fluctuations were observed for plasma beta-END throughout the menstrual cycle in the woman. Low beta-END concentrations were observed in the period preceding the LH preovulatory surge. Taken together, these results show that: (1) decreases in hypothalamic beta-END concentrations, which are controlled at least by circulating levels of 17 beta-E2, modulate GnRH synthesis and/or release and contribute to the mechanisms which initiate the LH surge; (2) anterior pituitary beta-END might be involved in the mechanisms which terminate the LH surge.