Corpus Luteum Production Research Articles

Follicle vascularity coordinates corpus luteum blood flow and progesterone production

Colour Doppler ultrasonography was used to compare the ability of preovulatory follicle (POF) blood flow and its dimensions to predict the size, blood flow and progesterone production capability of the subsequent corpus luteum (CL). Cows (n=30) were submitted to a synchronisation protocol. Follicles ≥7mm were measured and follicular wall blood flow evaluated every 12h for approximately 3.5 days until ovulation. After ovulation, cows were scanned daily for 8 days and similar parameters were evaluated for the CL. Blood samples were collected and plasma progesterone concentrations quantified. All parameters were positively correlated. Correlation values ranged from 0.26 to 0.74 on data normalised to ovulation and from 0.31 to 0.74 on data normalised to maximum values. Correlations between calculated ratios of both POF and CL in data normalised to ovulation and to maximum values ranged from moderate (0.57) to strong (0.87). Significant (P<0.0001) linear regression analyses were seen in all comparisons. In conclusion, higher correlations were observed between the dimensions of POF and/or CL and blood flow of both structures, as well as POF and/or CL blood flow with plasma progesterone concentrations of the resultant CL. These findings indicate that follicle vascularity coordinates CL blood flow and progesterone production in synchronised beef cows.

Prostaglandin biosynthesis, transport, and signaling in corpus luteum: a basis for autoregulation of luteal function.

The corpus luteum (CL) is a transient ovarian endocrine gland formed from the ovulated follicle. Progesterone is the primary secretory product of CL and is essential for establishment of pregnancy in mammals. In the cyclic female, the life span of CL is characterized by luteal development, maintenance, and regression regulated by complex interactions between luteotrophic and luteolytic mediators. It is universally accepted that prostaglandin (PG) F(2a) is the luteolysin whereas PGE(2) is considered as a luteotropin in most mammals. New emerging concepts emphasize the autocrine and paracrine actions of luteal PGs in CL function. However, there is no report on selective biosynthesis and cellular transport of luteal PGE(2) and PGF(2alpha) in the CL of any species. We have studied the expression of enzymes involved in the metabolism of PGE(2) and PGF(2alpha), cyclooxygenase (COX)-1 and -2, PGE and F synthases, PG 15-dehydrogenase, and PG transporter as well as receptors (EP2, EP3, and FP) throughout the CL life span using a bovine model. COX-1, PGF synthase, and PG 15-dehydrogenase are expressed at constant levels whereas COX-2, PGE synthase, PG transporter, EP2, EP3, and FP are highly modulated during different phases of the CL life span. The PG components are preferentially expressed in large luteal cells. The results indicate that PGE(2) biosynthesis, transport, and signaling cascades are selectively activated during luteal maintenance. By contrast the PGF(2alpha) system is activated during luteal regression. Collectively, our results suggest an integrated role for luteal PGE(2) and PGF(2alpha) in autoregulation of CL function.

Steroids as local regulators of ovarian activity in domestic animals

The presented overview gives clear evidence for steroids as local regulators of follicular and luteal activity. In the follicle, estrogen receptor-α (ERα) and ERβ expression are demonstrated in cow, ewe and pig. Besides species specific effects in general, there is evidence that estradiol-17β (E 2) exerts a dose-dependent inhibition on the secretion of progesterone (P 4) by both theca interna cells (TI) and granulosa cells (GC). GC enhance the ability of the TI to produce androstendione by supplying them with progestin precursor. Androgen produced by TI enhances the ability of the GC to make E 2, and high concentrations of E 2 in the preovulatory follicle inhibit 3β-HSD in both TI and GC and thus, may promote the use of the pathway Δ 5 for TI androgen production. The authors suggest that E 2 acts within the follicle to exert positive feedback on androgen and E 2 production, and exerts mitotic and anti-atretic or anti-apoptotic effects on follicular cells. Parts of the E 2-mediated local action are regulated by stimulating effects on hormone receptors (LH, FSH, oxytocin). Gap junctions permit transfer of nutrients and cytokines to and from the avascular GC and oocyte, and formation is stimulated by estrogens. In bovine corpus luteum (CL) there is evidence that P 4 may directly regulate the production of P 4, oxytocin and prostaglandins (PGs) in a cycle dependent fashion. In most of domestic animal species, there is clear evidence for CL production of E 2 with clear stimulatory and luteotropic effects on P 4, and an intraluteal circuit that involves paracrine effects of E 2, oxytocin and PGF 2α (especially in pigs). In contrast, there are species (ruminants, mares) in which the evidence for important local effects of E 2 is less clear, although expression of ERα, ERβ and progesterone receptor (PR) is documented. Progesterone is very important for the regulation of CL lifetime by effects on the endometrium and release of the luteolytic signal PGF 2α. In conclusion, steroids as local regulators of ovarian activity are now documented and may stimulate further research in this field.

Equine chorionic gonadotropin regulates luteal steroidogenesis in pregnant mares.

The onset of eCG secretion in pregnant mares coincides with an increase in luteal steroid production and a relative shift toward androgen and estrogen synthesis. However, a cause-effect relationship between eCG and the shift in luteal steroidogenesis has not been demonstrated. In this study, we have investigated the effect of eCG on steroid production by the corpus luteum (CL) during equine pregnancy. All mares were supplemented with 44 mg altrenogest (a progestogen) per day on Days 18-50. Increasing doses of eCG were administered on Days 26-28, before the onset of endogenous eCG secretion, to four mares with and four mares without a functional CL (prostaglandin F2alpha administered on Day 18). Four mares with a functional CL received no exogenous eCG. In eCG-treated mares without a functional CL, progestin, androstenedione, and estrogen concentrations did not significantly increase after exogenous eCG administration or endogenous eCG secretion. In eCG-treated mares with a functional CL, progestin and estrogen production increased significantly after exogenous eCG administration and endogenous eCG secretion, whereas androstenedione concentrations tended to increase following exogenous eCG and increased significantly following endogenous eCG secretion. In mares with a functional CL that did not receive exogenous eCG, progestin and estrogen concentrations increased and androstenedione concentrations tended to increase only after the onset of endogenous eCG secretion. These data demonstrate that the increase in luteal steroidogenesis that coincides with the onset of eCG secretion is induced by eCG and results in an increase in luteal androgen and estrogen synthesis. Our findings support the hypothesis that eCG has a luteotropic action in pregnant mares.

Comparative morphometric study of the endometrium, the fallopian tube, and the corpus luteum during the postovulatory phase in normally menstruating women

To compare function and histologic structure of the corpus luteum (CL) to the morphology of the endometrium and the fallopian tube in normally menstruating women. Circulating steroid and luteinizing hormone (LH) levels were compared with CL steroid production in vitro and the histology of CL, endometrium, and the fallopian tube at four stages of the postovulatory phase (days LH +/- 0/LH+3, LH+4/LH+7, LH+8/LH+11, LH+12/onset of menstruation). SETTING OF PATIENTS: The study included 28 volunteers with proven fertility undergoing surgical sterilization timed in relation to the LH surge. Blood and urine samples for LH, progesterone (P), and estradiol assessment were obtained before (simultaneously with ultrasound examinations), during, and after operation. Biopsy specimens from CL, endometrium, and fallopian tube were taken at the surgical sterilization and subjected to morphometric analyses. Significant correlation was found between the endometrial dating and the LH surge (r = 0.923) and between the dating of the endometrial and CL biopsies (r = 0.918). A significant correlation (P less than 0.01) existed between circulating P levels and two endometrial indices; the number of vacuolated cells (LH+4/LH+7) and the glandular diameter (LH+8/LH+11). In normally menstruating women, the endometrial biopsy is likely to closely gauge the CL activity provided the biopsy is timed in relation to the LH surge.

Surgical alteration of the mesosalpinx and its influence upon ovarian ovulatory function in the rabbit

Ovarian ovulatory function as correlated with the production of corpora lutea was studied in 58 rabbits that were subjected to unilateral surgical procedures. Initially, a resection of 50% of the isthmus and 50% (n = 8) or all (n = 8) of the corresponding mesosalpinx was performed. Next, 50% of the ampulla and 50% (n = 7) or all (n = 8) of the corresponding mesosalpinx was resected. Finally, a variable length, either one third, two thirds, or all, of the ampulla (n = 27) was dissected from the adjacent mesosalpinx. After natural copulation of the animals, without administration of gonadotropin, the numbers of corpora lutea on the operated and control sides were counted. A slight but nonsignificant overall reduction in corpora lutea on the operated side was observed. This showed no correlation either to the amount of mesosalpinx resected or the proximity of the surgical procedure to the ovary. Also, no correlation was observed with the length of the dissected ampullary part.

Ovulatory function after tubal microsurgical procedures in the rabbit

Ovulatory function as correlated with the production of corpora lutea was studied in 72 rabbits that were subjected to unilateral tubal microsurgical procedures. Isthmo-isthmic reanastomosis was performed in 11 rabbits, ampullo-isthmic reanastomosis in 10, and ampullo-ampullary reanastomosis in 11. In a second group of 40 animals, 20% to 100% of the isthmic portion (n = 20) and 20% to 60% of the ampullary portion (n = 20) were resected with reanastomosis. After natural copulation of the animals, without administration of gonadotropin, the numbers of corpora lutea on the operated and control side were counted. A slight but nonsignificant overall reduction in corpora lutea on the anastomosed side was observed. This showed no correlation to amount of tubal resection or proximity of the anastomosis to the ovary.

Effects of methylmercuric chloride on the progeny of mice and rats treated before or during gestation

Pregnant mice intubated with mercury as CH 3HgCl in doses of 0, 0·1, 1 or 5 mg Hg/kg/day from day 6 to day 17 of pregnancy, inclusive, were allowed to litter. Doses of 5 mg/kg/day caused 100% stillbirths or neonatal deaths but no apparent maternal toxicity. Doses of 1 mg/kg/day induced a transitory inhibition of cerebellar cellular migration from the external granular layer and depressed reactions of oxidative enzymes. These histological changes were not associated with any obvious adverse clinical effects and were not seen at lower doses. Weanling female rats were fed diets containing levels of 0, 0·002, 0·01, 0·05 or 0·25 mg Hg (as CH 3HgCl)/kg/day and were mated at maturity with untreated males. Some dams were killed at term and others were allowed to litter. No adverse effect was apparent in foetuses taken at term from dams given up to 0·25 mg Hg/kg/day. Postnatally, developmental defects of undetermined aetiology were observed in the eyelids in animals from all test groups and the controls. These were associated with histological changes in the harderian gland, the exorbital lachrymal gland and the parotid salivary gland. The incidence of ocular defects was dose-related and increased significantly in the group on 0·25 mg Hg/kg/day. Rats with ocular defects were killed and at weaning the remaining offspring from each group were distributed into two sub-groups, one of which was given the appropriate methylmercury-containing diet while the other was reared on control feed. Adult mating within each sub-group revealed that continuation or cessation of treatment with methylmercury had no effect on the production of corpora lutea or on reproductive performance.

On the control of follicular development in intrasplenic ovarian grafts by minute quantities of oestrogen.

introduction The control of ovarian endocrine function by oestrogen is known since almost twenty years (for references see Courrier 1945; Masson and Barsantini 1948; Robertson 1949). More recently it has been found in this Department that intrasplenic ovarian grafts in the guinea pig offer an excellent opportunity for a systematic study of the steroid control of follicular development dependent on hypophyseal gonadotrophins, the hypophysis being freed from the ovarian control since the steroids produced by the ovary itself are inactivated, when this device is used, in their passage through the liver. Hemorrhagic follicles (H.F.) and cystic follicles which are a characteristic feature of the intrasplenic graft in castrated females failed to appear when oestrogen absorbed from a subcutaneously implanted pellet of α-oestradiol was allowed to circulate in the body; production of corpora lutea was greatly enhanced. On the contrary, progesterone and desoxycorticosterone were shown to counteract luteinization (Lipschutz a. oth. 1948).3

CHANGES IN HORMONE CONTENT OF THE FEMALE RABBIT HYPOPHYSIS AFTER MATING

EXPERIMENTS cited by Hill (1) have shown that in the rabbit ovulation is brought about by a neuro-secretory mechanism. Impulses induced by copulation stimu late the anterior hypophysis to discharge gonadotropic hormones, which may then act upon the ovary to produce ovulation in from ten to twelve hours. Ovulation will not take place if the hypophysis is removed within one hourafter mating (2). Hill (1) has shown that there is a progressive decrease in gonadotropic potency of the rabbit hypophysis following mating, and that the lowest level of potency is reached in about 24 hours. The discharge from the hypophysis would thus appear to continue beyond the period required for ovulation. The hormones released in the postovula tory period may therefore be availablefor the production of corpora lutea and per haps for other processes. Hill's method of analysis, using the female rabbit in estrus as the test animal, gives a measure of the gonadotropic potency only, and does not per mit an estimation of the relativ...

Gonad-Stimulating Extract from Alfalfa Meal.

For reasons which can better be stated in a more complete report, it was thought highly probable that the pituitary hormone was not elaborated in the animal body from simple chemical substances, but on the contrary, was built up from complex precursors, or, taken in from the environment in a form not far removed from the hormone itself. If such hypothesis were correct, one should be able to isolate from foods these complex substances, or precursors, which when given to an animal in sufficient amounts, would prove to be gonad-stimulating. Of the foodstuffs considered, green plants seemed to be the most likely source of such material. Consequently, alfalfa was investigated from this standpoint and found to yield an extract capable of affecting the rabbit ovary in a fashion similar to that of the material found in pregnancy urine; i. e., the production of corpora lutea and corpora hemorrhagica in unmated rabbits.The extract is prepared by mixing 1 kilo of alfalfa meal with 10 liters of water and sufficient 3...

Anterior Pituitary Hormones Acting on the Ovary and Differences in the Reactions in Different Species.

There has been much discussion in recent literature as to whether the anterior pituitary gland produces one or 2 kinds of hormones which act on the mammalian ovary, and through the ovary on the uterus, vagina and mammary gland, or also directly on the last named organ. Zondek and others hold that there are 2 types of anterior pituitary hormones acting on the ovary, (1) the follicular growth hormone, responsible for the growth of follicles and (2) the luteinizing hormone causing the production of corpora lutea and of lutein tissue in general. As previously indicated, the facts which we have established as well as other facts only partly published can be explained most satisfactorily if we assume that there are at least 2 types of anterior pituitary hormones which act on the ovary, one of which affects also the thyroid gland. These 2 hormones are as follows: (1) A hormone (1) which is responsible for the increase in size of the ovarian follicles and for the maturation processes which take place in the granulosa of follicles. This hormone counteracts the tendency of the granulosa to undergo degeneration, leads to the maturation of the granulosa primarily of the large sized follicles, but may also cause beginning or further advanced maturation of the granulosa of medium-sized and even smaller follicles. If no inhibiting mechanisms are at work, the production of large mature follicles leads in due time to ovulation and to the formation of true corpora lutea with the consequences which follow from the functioning of these organs. However, in many other cases, the large-sized mature follicles do not give rise to ovulation, but an ingrowth of capillaries and of connective tissue cells from the theca interna into the granulosa of such follicles; this is followed by the transformation of the granulosa cells into lutein cells and is usually also accompanied by an increase in the size of the theca interna cells.