Changes in sex steroids, gonadotropins, prolactin, and inhibin in pregnant and nonpregnant Japanese black bears (Ursus thibetanus japonicus)

We examined changes in the concentrations of serum progesterone (P4), estradiol-17beta (E2), FSH, LH, prolactin (PRL), and inhibin to determine their interaction and their effect on the reproductive endocrine controls of pregnant and nonpregnant female Japanese black bears. Fourteen female bears were used in this study over a 2-yr period. In the first year, six of the bears were divided into two groups; a pseudopregnant group and a nonpregnant group. In the second year, the remaining eight bears were also divided into two groups; a pregnant group and a nonpregnant group. Pregnant and pseudopregnant bears had similar P4 trends with both groups exhibiting a significant increase in December, which is the suspected time of implantation in pregnant bears. These trends correlated with an increase in PRL levels, whereas low levels of LH were maintained throughout the year. Nonpregnant bears maintained low concentrations of P4, and compared with pregnant and pseudopregnant bears, they also exhibited a delayed elevation in PRL. Luteinizing hormone activity varied among individual animals, but regardless of reproductive status, fluctuation patterns of E2, FSH, and inhibin did not differ among bears. Our results suggest that PRL may play a luteotropic role in both pregnant and pseudopregnant bears, and is possibly responsible for inducing reactivation of the dormant corpus luteum that precedes implantation in the Japanese black bear.     

Endocrine Changes after Mating in Pregnant and Non-Pregnant Llamas and Alpacas

Plasma concentrations of oestradiol-17ß, progesterone, 15-keto–dihydro–PGF2α and luteinizing hormone (LH) were monitored in llamas and alpacas after mating with an intact male. Concentrations of LH and PGF2α metabolite were high immediately after copulation. Ovulation occurred in 92% of the animals. The first significant increases in progesterone were recorded on day 4 after mating. In non-pregnant animals the lifespan of the corpus luteum was estimated to be 8–9 days. Luteolysis occurred in association with the release of PGF2α. In pregnant animals, a transient decrease in progesterone concentrations was observed between days 8 and 18 in both species. No significant changes in PGF2α secretion were registered during this period. Oes– tradiol–17ß concentrations were high on the day of mating, declined to low values on day 4, and started to increase again on day 8. Peak values after luteolysis in non-pregnant animals were significantly higher than those registered in pregnant ones. Furthermore, concentrations of oestradiol-17ß were elevated for a longer period in non–pregnant than in pregnant animals. The results suggest that progesterone from the corpus luteum exerts a negative influence on follicular activity in pregnant animals by reducing oes– tradiol-17ß secretion.     

Oestradiol-17beta and progesterone in nymphomaniac cows

Oestradiol-17beta and progesterone were assayed in the plasma of 32 nymphomaniac cows. In 21 cases oestradiol-17beta concentrations were higher than those recorded during the preovulatory surge of normal cyclic cows. However, for a further 5 nymphomaniac cows oestradiol-17beta concentrations were within the range of those recorded in normal cows during the luteal phase. In 11 cases progesterone concentrations were higher than 1.5 ng/ml, but in only 5 of them could this have been due to a corpus luteum. The presence of progesterone, whether or not associated with a corpus luteum, did not determine the level of oestradiol-17beta. Therefore, nymphomania seems to be less a disease, per se, than a nonspecific symptom of ovarian perturbation.     

Prostaglandin E2 levels in uterine tissues and its relationship with uterine and luteal progesterone during the estrous cycle in dairy cows

Endometrial tissue homogenates obtained at luteal and follicular stages of the estrous cycle were determined for prostaglandin E(2) and progesterone contents by EIA and RIA, respectively. In Experiment 1, the concentrations and changes of PGE(2) in uterine tissues collected by biopsy before slaughfter and subsequent samples collected at 30, 60 and 90 min after slaughter were measured. No significant differences were observed in the concentration of PGE(2) preslaughter or at 30 and 60 min post slaughter. However, there was a significant decrease (P<0.01) in PGE(2) concentration 90 min post slaughter. In Experiment 2, the concentrations of PGE(2) in the ipsilateral and contralateral horns in relation to corpus luteum function were compared. A significant (P<0.05) interaction was found between stages of estrous cycle (luteal vs follicular) based on CL progesterone content, and type of uterine horn (ipsilateral vs contralateral) on uterine PGE(2) levels. The PGE(2) concentration was significantly higher (P<0.01) at luteal phase than at follicular phase. During the luteal phase PGE(2) concentrations in tissues of the uterine horn ipsilateral to the corpus luteum was significantly higher (P<0.01) than the contralateral horn. The PGE(2) concentration was low and did not differ significantly between horns during follicular phase. A parallel increase (luteal: high) and decrease (follicular: low) in PGE(2) and progesterone concentrations were observed. Correlations were observed for CL progesterone and uterine PGE(2) concentrations as well as for PGE(2) and progesterone concentrations in uterine tissues (r=0.70 and r=0.60, respectively). The results show that the increase in PGE(2) concentrations in uterine tissues coincides with the high uterine progesterone concentrations during luteal phase.     

Effects of corpus luteum removal on progesterone, estradiol-17 beta and LH in early pregnancy of the tammar wallaby, Macropus eugenii

The quiescent corpus luteum of female tammars was reactivated by removal of the pouch young (RPY). The reactivated corpus luteum was ablated 3 days after RPY. Plasma progesterone and oestradiol concentrations were measured by radioimmunoassay in these and in sham-operated controls. Excision of the CL abolished the rise in progesterone seen at Day 5-6 in the sham-operated animals (130.7 +/- 56.6 vs 452.4 +/- 176.0 pg/ml, mean +/- s.d.). By contrast, oestradiol-17 beta values increased within 6-16 h of CL excision to 16.3 +/- 6.9 pg/ml and remained high for 1-3 days while in the sham-operated animals there were less sustained and more variable peaks of 10-20 pg/ml between Days 3 and 5 (mean 12.0 +/- 3.6 pg/ml at Day 4-5). We conclude that the early transient increase in peripheral plasma of progesterone is of luteal origin but the source of the oestradiol remains unknown.     

Modulation of the action of chorionic gonadotropin in the baboon (Papio anubis) uterus by a progesterone receptor antagonist (ZK 137. 316)

Signals from the developing mammalian blastocyst rescue the corpus luteum (CL) and modulate the uterine environment in preparation for implantation and early pregnancy. Our previous studies demonstrated that both short- and long-term administration of chorionic gonadotropin (CG) markedly alters the morphology and the biochemical activity of the receptive endometrium. Because the effects of CG were superimposed on a progesterone-primed endometrium, this study was undertaken to determine if the inhibition of progesterone action by progesterone receptor antagonists (PRa) in intact and ovariectomized baboons would alter the action of CG on the endometrium at the time of uterine receptivity. In the short-term hCG-treated baboons, the PRa reduced the epithelial plaque reaction, completely inhibited alpha-smooth muscle actin (alphaSMA) expression in stromal fibroblasts, and induced the reappearance of the progesterone (PR) and estrogen (ERalpha) receptors in epithelial cells. However, this treatment protocol had no effect on the expression of glycodelin in the glandular epithelium. In contrast, glycodelin expression in addition to alphaSMA was suppressed in the ovariectomized animals. In the long-term hCG-treated baboons, the PRa had a similar effect on both alphaSMA, PR, and ER. In addition, this treatment also resulted in an inhibition of glycodelin expression in the glandular epithelium. These results indicate that blocking the action of progesterone on the endometrium even for a short period of time has a profound effect on the hCG-induced response in stromal fibroblasts. In contrast, for the diminution of glandular epithelial function in the presence of an ovary requires prolonged inhibition of progesterone action, suggesting a potential paracrine effect on the endometrium from the CL in response to hCG.     

Effect of the regressing corpus luteum of pregnancy on ovarian folliculogenesis after parturition in cattle.

In cattle, the first postpartum dominant follicle has a predilection for the ovary contralateral to the previously gravid uterine horn, possibly due to a local inhibitory effect of the regressing corpus luteum of pregnancy in the ipsilateral ovary. The aim of the present study was to test the hypothesis that the regressing corpus luteum of pregnancy suppresses folliculogenesis in the ipsilateral ovary after parturition. Dairy cows were treated with prostaglandin F2alpha between 190 and 220 days of gestation to cause luteolysis without inducing parturition (n = 14) or were untreated controls (n = 32). Follicular growth and function were monitored by daily transrectal ultrasonography and collection of plasma samples for estimation of FSH, estradiol, and progesterone concentrations. The proportion of first dominant follicles in the ipsilateral ovary was similar for treated and control animals (4/14 vs. 8/32), as was the time interval between calving and establishment of a dominant follicle (mean +/- SEM, 10.1 +/- 0.4 vs. 10.7 +/- 0.5 days). Furthermore, no significant effect of treatment on dominant follicle growth or function was found as determined by plasma hormone concentrations. Although greater folliculogenesis was found in the ovary contralateral to the previously gravid uterine horn, once the location of the future first dominant follicle was selected, the timing of events was independent of location. We suggest that the corpus luteum of pregnancy does not have a local effect on postpartum ovarian folliculogenesis and that, instead, an effect of the previously gravid uterine horn shortly after parturition should be considered.     

Plasma and fecal progestagen evaluations during and after the breeding season of the female vicuna (Vicuna vicuna )

Plasma and fecal progestagen patterns of female (n = 10) vicunas (Vicuna vicuna ) were determined about 1 to 2 mo before and until 4 mo after breeding. The vicunas were caught wild and were penned at the Lauca National Park (Chile, 4470 m above sea level) for 7 mo (December to June). Plasma and fecal samples before and during the mating period (January to March) were collected 4 to 5 times weekly, and once or twice weekly thereafter. The samples were analyzed by enzymeimmunoassays (EIA) using antibodies against progesterone and 20alpha-dihydroprogesterone. High performance liquid chromatography (HPLC) separations confirmed that progesterone and 20alpha-dihydroprogesterone predominated in the plasma, whereas in the feces several unconjugated, immunoreactive progestagen metabolites containing either a 20-oxo- or a 20alpha-OH-group occurred. The coefficients of correlation (n = 409; P < 0.01) between matched plasma and fecal samples were 0.39 and 0.53 for 20-oxo- and 20alpha-progestagens, respectively. Elevated (5 to 6 d) plasma and corresponding fecal progestagens after mating indicated cyclic corpus luteum activity in 5 of the animals. After the mating period (23.2 +/- 3.3 d), corpus luteum function in these 5 animals persisted, as it did in 3 other animals that were not observed to be mating. The persisting corpus luteum function was demonstrated by increased mean plasma and fecal progestagen concentrations (> 1 ng/ml and > 100 ng/g, respectively). Mean plasma 20alpha-dihydroprogesterone concentrations exceeded that of progesterone by about 1 ng/ml (P < 0.01). The results demonstrated that in addition to plasma progesterone, plasma 20alpha-dihydroprogesterone and noninvasive fecal progestagen evaluations are useful, valid tools for determining corpus luteum function in vicunas.     

Concentrations of oestradiol-17β and progesterone in the plasma of dairy heifers before and after cloprostenol-induced and natural luteolysis and during early pregnancy

Plasma oestradiol-17β and progesterone levels were measured in seven nulliparous, dairy heifers (British Friesian breed) that were administered cloprostenol (a synthetic analogue of prostaglandin F_2α) between days 8 and 14 of the oestrous cycle and inseminated (AI) 72 and 96 h later, and in seven heifers inseminated (AI) at natural oestrus.In both treated and untreated heifers, the beginning of the progesterone fall and the oestradiol-17β rise associated with luteolysis appeared to be synchronous but, whereas the rate of fall in progesterone level was greater for the treated heifers, that of the oestradiol-17β rise did not differ between treated and untreated heifers. Mean pre-ovulatory peaks of oestradiol-17β were 8 pg/ml and 10 pg/ml for treated and untreated heifers respectively.A post-ovulatory peak of oestradiol-17β in plasma 5–6 days after the pre-ovulatory peak occurred in all heifers whether or not conception had taken place. It is suggested that 7 days after the initiation of oestradiol-17β secretion by the pre-ovulatory follicle, another follicle begins to mature and secrete oestradiol-17β and that the progress of the latter towards full maturation and potential ovulation is stopped by rising progesterone levels from the corpus luteum; as a result in normal, non-pregnant cattle an interval of about 21 days elapses before another ovulation (of another follicle) takes place. In the event of premature luteolysis (in the present study induced between the 8th and 14th day) there is no evidence that the timing of this luteolysis influences the time taken for a follicle to enter the final stages of pre-ovulatory maturation, when increasing amounts of oestradiol-17β are secreted. Thus the interval between ovulations may not be less than 7 days but, depending on corpus luteum survival, may vary between 7 and 21 days.In one heifer after natural luteolysis a normal plasma oestradiol-17β peak followed but this was not associated with ovulation and corpus luteum formation. The second oestradiol-17β peak 6 days after the first, however, evidently assumed the ovulatory role; presumably the secreting follicle concerned, not being subject to inhibition by progesterone rising to luteal levels, matured fully and ovulated. Thus the second, normally post-ovulatory, oestradiol-17β peak in cattle can, in the event of failure of ovulation at the normal time, itself assume the ovulatory function, the oestrous cycle length then being about 28 days.     

Corpus luteum size and plasma progesterone concentration in cows

It is often assumed that a larger corpus luteum will produce more progesterone and generate higher circulating plasma concentrations. The aim of the study was to determine whether the size of the corpus luteum does actually determine circulating plasma progesterone concentrations. Data were collated from a number of studies on various aspects of luteal function in non-lactating dairy cows to allow comparisons to be made between corpus luteum weight and plasma progesterone concentration across the luteal phase. In these studies oestrous cycles had been synchronised and animals slaughtered on day 5, day 8 or day 16 following oestrus. Both corpus luteum weight and plasma progesterone concentration increased between day 5 and day 8. Plasma progesterone concentration but not luteal weight also increased between day 8 and day 16. On day 5 there was a strong relationship between corpus luteum weight and plasma progesterone (R² = 0.64; P < 0.001). However, no such relationship was present on day 8 or day 16. These results indicate that while during the early stage of corpus luteum development a relationship between size and progesterone is present, by day 8 of the cycle, the size of the corpus luteum is no longer of importance in determining circulating progesterone concentrations.     

The influence of ovarian activity and uterine involution determined by ultrasonography on subsequent reproductive performance of dairy cows

The objective of this study was to test the hypothesis that a follicle >8 mm diameter in the ovary ipsilateral to the previously gravid uterine horn (PGUH), between 14 and 28 days postpartum, improves subsequent reproductive performance. Lactating Holstein-Friesian cows (n=284) in 3 commercial herds were examined using transrectal ultrasonography once between 14 and 28 days postpartum to determine associations between uterine and ovarian measurements and subsequent fertility. There were fewer cows with a corpus luteum in the ovary ipsilateral to the PGUH compared with the contralateral ovary (16.9% vs. 37.0%; P<0.001). In addition, in the ovary ipsilateral to the PGUH there were fewer follicles >5 mm diameter (mean +/- SEM; 0.69 +/- 0.06 vs. 1.02 +/- 0.06; P<0.001) and fewer animals with a follicle >8 mm diameter (26.1% vs. 49.6%; P<0.001). These differences between the ovaries ipsilateral or contralateral to the PGUH declined with increasing time between 14 and 28 days postpartum. The presence of a purulent vaginal discharge decreased the number of animals with a corpus luteum in the ovary contralateral to the PGUH (45/143 vs. 60/141; P<0.05), but not in the ovary ipsilateral to the PGUH. The presence of a follicle >8 mm diameter in the ovary ipsilateral to the PGUH was associated with a shorter calving to conception interval compared with animals without such a follicle (99.0 +/- 5.6 days, n=74, vs. 112.8 +/- 4.4 days, n=210; P<0.05). These observations raise an intriguing issue: how does this follicle affect subsequent fertility--does the follicle exert a local influence on the uterus, or vice versa?     

Placental and luteal steroidogenesis in the pregnant rhesus monkey.

Progesterone, 20alpha-dihydroprogesterone, estrone and estradiol-17beta concentrations were estimated by radioimmunoassay in blood plasma from uterine, uteroovarian and femoral veins of rhesus monkeys (Macaca mulatta) on days 22, 49, 128 and 160 of gestation. Steroids were consistently more concentrated in uterine and uteroovarian that in femoral venous plasma and in many cases levels in the uteroovarian vein were also higher than those in the uterine vein indicating luteal secretion of both progestins and estrogens thoughout gestation. In some animals, however, the corpus luteum appeared quiescent. As reflected in the decline in the uterine venous progesterone/estradiol-17beta concentration ratio, a shift in steroid contribution from the uterus and its contents occurred between days 22 and 49 of gestation with progesterone declining more rapidly than estradiol-17beta. Progesterone/20alpha-dihydroprogesterone was higher in both uterine and uteroovarian than in femoral venous plasma suggesting peripheral metabolism of progesterone to 20alpha-dihydroprogesterone.     

Progesterone values in monkeys near term

The serum progesterone of peripheral, ovarian, uterine and umbilical blood from six Macaca mulatta and two M. fascicularis was determined by radioimmunoassay in late pregnancy. Peripheral progesterone values fell to lower levels the day after delivery, a decrease indicating placental progesterone secretion. The concentration of progesterone in the ovarian vein associated with the presence of a corpus luteum was greater than that in the contralateral vein, a difference denoting active progesterone secretion by the corpus luteum. In most cases the uterine vein on the side associated with the placement of the primary and secondary placentae contained more progesterone than its opposite counterpart, a condition that suggests some synthesis of progesterone by the placenta. The umbilical vein/artery progesterone ratio showed fetal metabolism of this steroid and also greater metabolism of progesterone by the female fetus. The progesterone concentration in the ovarian vein associated with the corpus luteum in mothers who bore female fetuses was greater than that of the same vein in those mothers who bore male fetuses. Peripheral progesterone levels were high the day before cesarean section and fell to lower levels the day after delivery. The decline was more rapid in mothers who bore male fetuses.     

Distribution of progesterone to the uterus and associated vasculature of cattle

Multiparous dairy cows were sampled to study the concentrations of progesterone in tissue of the uterus and associated vasculature and to determine whether progesterone was delivered to the uterus locally. In study 1, progesterone was greater (p less than or equal to 0.05) in the first venous branch draining the cranial portion of the uterine cornu adjacent to the vary with a corpus luteum than in jugular blood or in the same vein draining the opposite uterine cornu on day 11 postestrus. Concentrations of progesterone were also greater (p less than or equal to 0.05) in the cranial than in the caudal half of the uterine cornu adjacent to the luteal-bearing ovary or in the cranial and caudal halves of the opposite uterine cornu. Concentrations of progesterone were also greater (p less than or equal to 0.05) in the uterine or ovarian arterial tissue adjacent to the ovary with the corpus luteum than in those same vessels on the contralateral side. In a second study, progesterone at 0 h on day 11 postestrus was greater (p less than or equal to 0.05) in the first venous branch draining the cranial portion of the uterine horn adjacent to the luteal-bearing ovary than in jugular blood, the same vein in the contralateral uterine cornu or in the same uterine vein 48 h after ligation and resection of the oviductal vein adjacent to the ovary with the corpus luteum. It is concluded that progesterone is delivered locally to the uterus and associated vasculature and the route of local delivery appears to be via the oviductal vein.     

Steroid hormone modulation of prostaglandin secretion in the ruminant endometrium during the estrous cycle

Prostaglandins, produced from membrane phospholipids by the action of phospholipase A2, cyclooxygenase, and specific prostaglandin synthases, are important regulators of ovulation, luteolysis, implantation, and parturition in reproductive tissues. Destruction of the corpus luteum at the end of the estrous cycle in nonpregnant animals is brought about by the pulsatile secretion of prostaglandin F(2alpha) (PGF(2alpha)) from the endometrium. It has been known for many years that progesterone, estradiol, and oxytocin are the hormones responsible for luteolysis. To achieve luteolysis, two independent processes have to be coordinated; the first is an increase in the prostaglandin synthetic capability of the endometrium and the second is an increase in oxytocin receptor number. Although progesterone and estradiol can modulate the expression of the enzymes involved in prostaglandin synthesis, the primary reason for the initiation of luteolysis is the increase in oxytocin receptor on the endometrial epithelial cells. Results of many in vivo studies have shown that progesterone and estradiol are required for luteolysis, but it is still not fully understood exactly how these steroid hormones act. The purpose of this article is to review the recent data related to how progesterone and estradiol could regulate (initiate and then turn off) the uterine pulsatile secretion of PGF(2alpha) observed at luteolysis.     

Development of corpus luteum susceptibility to an analog of prostaglandin F2α, throughout the luteal phase in llamas (Lama glama)

The aim of the present study was to evaluate the susceptibility of the corpus luteum to d-cloprostenol (synthetic analog of PGF(2α)) throughout the luteal phase in llamas. Female llamas (n=43) were induced to ovulate by GnRH injection in the presence of an ovulatory follicle and randomly assigned into one of six groups: control and treated with an injection of d-cloprostenol on Day 3, 4, 5, 6 or 8 post GnRH. Blood samples were collected to determine plasma progesterone concentrations. There was no effect of treatment on animals injected on Day 3 or 4 post-GnRH. In animals treated on Day 5, different responses were observed. No effect of treatment was recorded in 27% of the animals whereas 55% of the llamas showed a transitory decrease followed by a recovery in plasma progesterone concentrations after d-cloprostenol injection, indicative of a resurgence of the corpus luteum, extending the luteal phase a day more than in control animals. In the remaining 18% of the animals injected on Day 5, (corresponding to those exhibiting the greatest plasma progesterone concentrations at the day of injection), complete luteolysis was observed. Plasma progesterone concentrations decreased to below 1 ng ml(-1) 24 h after d-cloprostenol in llamas injected on Day 6 or 8 post-GnRH. In conclusion, the corpus luteum of llamas is completely refractory to PGF(2α) until Day 4 after induction of ovulation, being partially sensitive by Day 5 and fully responsive to PGF(2α), by Day 6 after induction of ovulation.     

Prostaglandin F and progesterone secretion by porcine endometrium and corpus luteum in vitro

Slices of porcine endometrium and corpus luteum tissue obtained from mature sows throughout the luteal phase of the oestrous cycle were incubated in culture medium which was analysed at regular intervals over a period of 8 hours for prostaglandin F and progesterone. Prostaglandin F secretion was greatest by endometrium obtained during the mid III to late I luteal stage of the cycle and the increased levels secreted by this tissue were paralleled by high levels of secretion from corpus luteum tissue. The addition of indomethacin (10 μg/ml) to the culture medium completely abolished prostaglandin F secretion by both endometrium and luteal tissue indicating that the high levels of the prostaglandin were due to synthesis. Progesterone secretion by the corpus luteum was maximal from early luteal tissue and had declined to considerably lower levels by late stage tissue when prostaglandin secretion was greatest. The possible physiological significance of luteal prostaglandin F secretion is discussed.     

Pregnancy rates relating to plasma progesterone levels in recipient heifers at day of transfer

A group of Holstein heifers (n=223), weighing approximately 454 kg, were used to determine pregnancy rates in relation to plasma progesterone concentrations in recipients on the day of embryo transfer. All recipients were in estrus within +/- 12 hours of the donor cows. These data showed a cubic trend by regression analysis. Chi-square test revealed that there was a significant (P<0.0001) relationship between plasma progesterone concentrations and resulting pregnancies. Pregnancy rates were low when plasma progesterone concentrations were below 2.00 ng/ml. Actual number of pregnancies relating to specific plasma progesterone groups were 12 61 (20%) for <2.00 ng/ml, 94 127 (74%) for concentrations between 2.00 and 5.00 ng/ml, and 21 35 (60%) for >5.00 ng/ml. Corpora lutea were classified as good, poor, or cystic by both manual and visual observation. These observations revealed that manual palpation of the corpus luteum was not a valid criterion of the corpus luteum function as measured by plasma progesterone concentrations. Further observation revealed no significant relationship between plasma progesterone and whether the corpus luteum was on the left or right ovary. Hence, pregnancy rate was not significantly associated with the left or right ovary. Pregnancies were determined by rectal palpation at 60 days.     

Photoperiod and delayed implantation in the northern fur seal (Callorhinus ursinus)

An equation for determination of the photoperiod at any given latitude for any given date is presented and used in an analysis of reproductive timing in the northern fur seal in which there is an obligatory delay of implantation. Fur seals breeding on San Miguel Island, California (33 degrees N) displayed a mean date of parturition that was 14 days earlier (P less than 0.001) than that of the parent stock on the Pribilof Islands, Alaska (57 degrees N). Previous studies have shown that changes occur in the corpus luteum, in follicles in the ovary containing the corpus luteum, in concentrations of plasma progesterone and oestradiol-17 beta, and in the uterine lining when there is a mean photoperiod of 12.5 h/day. This photoperiod occurs at both locations at 62 days after the mean dates of parturition, and may act as a cue for the initiation of implantation in these seals.