233 Estrus Response and Pregnancy Rates of Beef Replacement Heifers Enrolled in Two Fixed-time Artificial Insemination Protocols, with or Without Pre-synchronization

Pre-synchronization strategies with prolonged exposure to exogenous progesterone have the potential to alter estrus expression and improve fertility in replacement beef heifers. The objective of this study was to evaluate the estrus response and pregnancy rate of beef heifers enrolled in two fixed-time artificial insemination (TAI) protocols. A total of 306 heifers (14 ± 2 months of age; 372 ± 24 kg body weight [BW]) at three locations were enrolled in the study. Within location, heifers were stratified by age and BW and randomly assigned to one of two treatments: 1) PG-CIDR54 (n = 152), heifers were administered prostaglandin F2α (PGF; 25 mg) and a controlled internal drug releasing (CIDR) insert (Day -14), an injection of GnRH [100 μg (Day -7)], PGF injection and CIDR removal (Day 0), and a second injection of GnRH concurrently with TAI 54 ± 2 h later (Day 2); 2) 7-day CO-Synch+CIDR (CTRL; n = 154), heifers were administered GnRH (100 μg) and a CIDR insert (Day -7), PGF (25 mg) injection and CIDR removal (Day 0), and a second injection of GnRH concurrently with TAI 54 ± 2 h later (Day 2). All heifers received an estrus alert patch on Day 0 and were evaluated for patch activation at TAI on Day 2. Pregnancy was diagnosed by transrectal ultrasonography between 35 and 55 days after TAI. The percentage of heifers exhibiting estrus between Day 0 and 2 was greater (P < 0.01) in PG-CIDR54 compared with CTRL (77.0 and 39.6%, respectively). In addition, pregnancy rate to TAI tended (P = 0.08) to be greater for PG-CIDR54 compared with CTRL (48.0 and 38.3%, respectively). We conclude that beef heifers enrolled in the PG-CIDR54 protocol had increased estrus expression and tended to have greater pregnancy rate when compared with heifers enrolled in the 7-day CO-Synch+CIDR protocol.

Regression of Multiple Meningiomas after Discontinuation of Chronic Hormone Therapy: A Case Report

Introduction Meningiomas are more common in females and frequently express progesterone and estrogen receptors. Recent studies have revealed a high incidence of meningiomas in situations in which estrogen/progesterone levels are increased such as pregnancy, gender reassignment therapy, and fertility treatment. While the relationship remains unclear and controversial, these findings suggest exposure to high levels of endogenous or exogenous hormones may increase the risk of developing a meningioma. Patients and Methods A 40-year-old female with a history of endometriosis treated with chronic progesterone therapy presented with a visual deficit and was found to have multiple meningiomas, which regressed after cessation of exogenous progesterone. Conclusion A history of chronic hormone therapy should be included when evaluating patients diagnosed with meningiomas, particularly at a younger age and with multiple meningiomas. Cessation of exogenous progesterone resulting in regression of meningiomas suggests a direct action of progesterone on growth. Future studies are warranted to better elucidate this relationship.

Progesterone Positive Feedback on Pulsatile LH Secretion and FSH Release May Be Blunted in Estradiol-Pretreated Women With PCOS

In women pretreated with estradiol (E2), exogenous progesterone (P4) acutely augments LH and FSH release (P4 positive feedback). Women with PCOS exhibit impaired P4 negative feedback on LH pulse frequency, but it remains unclear whether such women exhibit impaired P4 positive feedback on LH/FSH release. We sought to explore the latter notion as an a priori secondary hypothesis in a study primarily designed to assess whether P4 acutely suppresses LH pulse frequency. We studied 12 women with PCOS and 12 normally-cycling, non-hyperandrogenic controls. After 3 days of transdermal E2 pretreatment (0.2 mg/day), subjects were admitted to the Clinical Research Unit (CRU) for a 24-hour frequent blood sampling protocol starting at 2000 h. (CRU admissions occurred no earlier than cycle day 7 in PCOS and between days 7 and 11 inclusive in controls.) At 0600 h, subjects received either 100 mg oral micronized P4 or placebo (PBO). In a subsequent menstrual cycle, subjects underwent an identical CRU protocol except that P4 was exchanged for PBO or vice versa. LH secretion was analyzed using Autodecon, a deconvolution program that provides estimates of LH pulse frequency, pulsatile LH secretion (amount of LH secreted as pulses), and basal (non-pulsatile) LH secretion. Results were analyzed using 2-period crossover design analysis of covariance. In both groups, neither LH pulse frequency nor basal LH secretion changed significantly with P4 (compared to changes with PBO). Mean LH increased with P4 in both groups—3.1-fold (95% CI, 2.4–4.0) in controls and 2.7-fold (95% CI, 2.1–3.5) in PCOS; in both groups, P4-related changes were significantly greater than PBO-related changes (Bonferroni-corrected p=0.012 and 0.010, respectively). In controls, pulsatile LH secretion increased 3.5-fold (95% CI, 2.3–5.2) with P4—significantly more than with PBO (p=0.029); while in PCOS, a 2.6-fold (95% CI, 1.8–3.9) increase with P4 was not significantly different from changes with PBO (p=0.911). In controls, mean FSH increased 2.0-fold (95% CI, 1.7–2.3) with P4—significantly more than with PBO (p=0.004); but in PCOS, a 1.5-fold (95% CI, 1.3–1.8) increase was not significantly different from changes with PBO (p=0.072). Despite the above, between-group (PCOS vs. controls) differences in P4-induced changes in pulsatile LH secretion and mean FSH were not formally (statistically) demonstrable. Between-group differences representing potential confounders included age (median 25.5 vs. 19.0 y; p=0.029), body mass index (29.9 vs. 21.8 kg/m2; p=0.006), and cycle day of CRU admissions (day 45.0 vs. 10.4 for P4 admissions; 30.0 vs. 10.0 for PBO admissions). In summary, these data suggest that P4-induced increases in pulsatile LH secretion and mean FSH may be blunted in PCOS compared to controls, which could contribute to ovulatory dysfunction in PCOS. However, our results do not confirm this possibility, and further study is needed.

Pre-implantation exogenous progesterone and pregnancy in sheep. II. Effects on fetal-placental development and nutrient transporters in late pregnancy

Background Administration of progesterone (P4) to ewes during the first 9 to 12 days of pregnancy accelerates blastocyst development by day 12 of pregnancy, likely due to P4-induced up-regulation of key genes in uterine epithelia responsible for secretion and transport of components of histotroph into the uterine lumen. This study determined if acceleration of blastocyst development induced by exogenous P4 during the pre-implantation period affects fetal-placental development on day 125 of pregnancy. Suffolk ewes (n = 35) were mated to fertile rams and assigned randomly to receive daily intramuscular injections of either corn oil vehicle (CO, n = 18) or 25 mg progesterone in CO (P4, n = 17) for the first 8 days of pregnancy. All ewes were hysterectomized on day 125 of pregnancy and: 1) fetal and placental weights and measurements were recorded; 2) endometrial and placental tissues were analyzed for the expression of candidate mRNAs involved in nutrient transport and arginine metabolism; and 3) maternal plasma, fetal plasma, allantoic fluid, and amniotic fluid were analyzed for amino acids, agmatine, polyamines, glucose, and fructose. Results Treatment of ewes with exogenous P4 did not alter fetal or placental growth, but increased amounts of aspartate and arginine in allantoic fluid and amniotic fluid, respectively. Ewes that received exogenous P4 had greater expression of mRNAs for SLC7A1, SLC7A2, SLC2A1, AGMAT, and ODC1 in endometria, as well as SLC1A4, SLC2A5, SLC2A8 and ODC1 in placentomes. In addition, AZIN2 protein was immunolocalized to uterine luminal and glandular epithelia in P4-treated ewes, whereas AZIN2 localized only to uterine luminal epithelia in CO-treated ewes. Conclusions This study revealed that exogenous P4 administered in early pregnancy influenced expression of selected genes for nutrient transporters and the expression of a protein involved in polyamine synthesis on day 125 of pregnancy, suggesting a ‘programming’ effect of P4 on gene expression that affected the composition of nutrients in fetal-placental fluids.

Prenatal exposure to exogenous progesterone adversely affects fetal development in Albino rats

Background The current study was carried out to investigate the effects of exogenous progesterone on fetal development in rats. Results Placental weights did not vary in control and treated groups. Fetal weights were significantly reduced in the low- and high-dose progesterone groups. Fetal CVL was significantly reduced in both treatment groups compared to control group. In fetuses that received maternal treatment with low- and high-dose progesterone, several parts of the fetal skeleton showed incomplete ossification. Alkaline phosphatase was decreased in the bones of fetuses born to progesterone-treated dams. The testes and ovaries of the fetuses of the dams treated with low and high doses of progesterone showed degenerative seminiferous tubules and failed sex cord development into primordial follicles, respectively. Conclusions The administration of exogenous progesterone during pregnancy adversely influences fetal growth, skeletal construction, and sex organ development.

Pre-implantation exogenous progesterone and pregnancy in sheep: I. polyamines, nutrient transport, and progestamedins

Background Administration of exogenous progesterone (P4) to ewes during the pre-implantation period advances conceptus development and implantation. This study determined effects of exogenous P4 on transport of select nutrients and pathways that enhance conceptus development. Pregnant ewes (n = 38) were treated with either 25 mg P4 in 1 mL corn oil (P4, n = 18) or 1 mL corn oil alone (CO, n = 20) from day 1.5 through day 8 of pregnancy and hysterectomized on either day 9 or day 12 of pregnancy. Endometrial expression of genes encoding enzymes for synthesis of polyamines, transporters of glucose, arginine, and glycine, as well as progestamedins was determined by RT-qPCR. Results On day 12 of pregnancy, conceptuses from P4-treated ewes had elongated while those from CO-treated ewes were spherical. The mRNA expression of AZIN2, an arginine decarboxylase, was lower in endometria of P4-treated than CO-treated ewes on day 9 of pregnancy. Expression of FGF10, a progestamedin, was greater in endometria of CO and P4-treated ewes on day 12 of gestation in addition to P4-treated ewes necropsied on day 9 of gestation. Treatment with P4 down-regulated endometrial expression of amino acid transporter SLC1A4 on day 12 of pregnancy. Conclusions Results indicated that administration of exogenous P4 during the pre-implantation period advanced the expression of FGF10, which may accelerate proliferation of trophectoderm cells, but also was correlated with decreased expression of glycine and serine transporters and polyamine synthesis enzyme AZIN2. Further research with increased sample sizes may determine how differential expression affects endometrial functions and potentially embryonic loss.