Endometrial prostaglandins (PGs) play a role in menstruation in primates and in luteolysis in nonprimates. Their biosynthesis is regulated by estrogen (E) and progesterone (P) in a manner not fully understood. The purpose of this thesis research was to (1) study the effects of E and P, both in vivo and in vitro, on basal endometrial PG output in vitro during the course of the artificial menstrual cycle in the rhesus monkey, and (2) further to examine the cellular mechanisms of P action in vivo on PG output using an ovine model system. To carry out the first objective, ovariectomized rhesus monkeys (n=39) were maintained on either a standard or manipulated artificial menstrual cycle (SAMC and MAMC, respectively) and endometrial biopsies were obtained at precise times in separate cycles on: cycle day 9 (mid-proliferative), 13 (mid-cycle E peak), 14 (one day post E peak), and 23 (mid-secretory). PGF2α was the most abundant PG produced in vitro by endometrial organ cultures, the levels of which changed most dramatically throughout the SAMC. Within the first 24 hours of organ culture, PGF2α accumulation was low on day 9 and rose significantly (p<0.01) on day 13, indicating a stimulatory effect of E in vivo. However, E added in vitro, at either physiologic or supraphysiologic concentrations, to endometrial cultures did not stimulate PGF2α accumulation on any cycle day examined. On day 14, just one day post E peak, there was a dramatic fall in PGF2α accumulation which appeared to be due to both a decline in stimulatory E in vivo and a rise in inhibitory P in vivo. Basal PGF2α accumulation in vitro by day 23 endometrial cultures was 10-fold higher (p<0.01) compared to days 9 and 14. This high level of PGF2α output on day 23 appeared to be caused by a paradoxical priming effect of P in vivo and also a slight enhancement by the mid-cycle peak of E in vivo. Padded in vitro, at a physiologic concentration, to day 23 endometrial cultures markedly inhibited (p<0.01) the high level of PGF2α accumulation, suggesting that P withdrawal in vivo promotes the rise in endometrial PGF2α production in vivo at the time of menstruation in primates. An ovine model system was further used to investigate the cellular mechanisms of P action in vivo. Ovariectomized sheep (n=8) were administered an infusion regimen of either E and P, or E and P vehicle alone, to examine the effects of P in vivo on PGF2α production in vitro by endometrial explants during short-term incubations. P in vivo increased the mass amount of stimulated PGF2α output by both physiologic and pharmacologic mechanisms. In addition, P did not appear to significantly alter the sensitivity of the endometrium to stimulatory levels of oxytocin in vitro indicating that the cellular events accounting for the P priming effect, in part, may occur independent of the oxytocin receptor closer to the PG biosynthetic pathway. In P-primed endometrium, the mass amount of PGF2α stimulated by a calcium-ionophore (A23l87) was less than that stimulated by OT suggesting the involvement of calcium-insensitive mechanisms in PGF2α synthesis.

The effects of energy balance on hormonal patterns and recovered oocytes were evaluated in 20 lactating Holstein cows during two trial periods (fall/spring). Cows were randomly selected and assigned to one of two dietary treatments formulated so that cows consumed 3.6% BW (HE- 1.78 mcal/kg; n=6 in fall, n=5 in spring) and 3.2% BW (LE-1.52 mcal/kg; n= 5 in fall, n=4 in spring). Body weight and body condition score (BCS) were recorded prior to parturition and weekly throughout the fall trial. Ultrasound guided transvaginal follicular aspirations were conducted twice weekly between d 30 and 100 of lactation. Follicle size and number were recorded. Follicular fluid (FF) was aspirated from the largest follicle, and serum samples were collected for hormone assay (IGF-1; estradiol (E2); progesterone (P4, serum ); LH and FSH). Oocytes were collected and graded based upon cumulus density and ooplasm homogeneity, then fertilized and cultured in vitro. Milk yield averaged 41.64 ± .3 kg/d (mean ± SE) for HE and 32.8 ± .3 kg/d for LE. There was a significant cubic day postpartum by treatment interaction for milk yield. Dry matter intake and BW treatment by week interactions were significant for the cubic and linear components, respectively. Oocyte numbers increased linearly from d 30 to 100 postpartum. HE cows produced more good + oocytes (1.5 ± .2 ) than LE cows (1.4 ± .1). Follicles less than or equal to 5 mm predominated throughout the study (6.4 ± 3.0). However, greater numbers of follicles 10 to 14 mm and greater than or equal to 15 mm were found in the fall (1.98 ± .08 and .50 ± .06) than spring (1.11 ± .3 and .23 ± .07). Follicular fluid IGF-1 was higher in HE (2.3 ± .2 ng/ml) than in LE cows (1.6 ± .2 ng/ml). Mean basal serum FSH concentration was lower at 28 d postpartum (173 ± 8 pg/ml) compared to later (521 ± 25 at d 60 and 650 ± 25 pg/ml at d 110). Serum P4 peaked at 35 d postpartum, with HE cows having 1 ng/ml higher P4 than LE cows. Low dietary energy reduced milk yield, DMI, BCS, FF IGF-1 and serum P4 and had a negative impact on oocyte quality. / Master of Science

<p dir="ltr">The vaginal microbiome and female sex hormones are both involved in the development and progression of gynecological pathologies. The individual mechanisms by which the vaginal microbiome leads to disease progression and how female sex hormones are known. However, the mechanisms by which the vaginal microbiome regulates female sex hormones, such as progesterone, are not well understood. This study seeks to understand how the vaginal microbiome regulates progesterone receptor (PGR) expression via secondary analysis of host and vaginal microbiome multi-omics data from the Partners PrEP cohort. This dataset consists of cervicovaginal samples of women enrolled in the Partners PrEP study. Partial Least Squares Regression (PLSR) models were created for each biological data type (microbial composition, metabolomics, metaproteomics) to assess how these factors regulate PGR expression. Significant factors were identified through variable importance of projection (VIP) and correlation analysis. Partial correlation analysis and follow-up PLSR models incorporating clinical and demographic variables were performed to assess the robustness of the vaginal microbiome-PGR associations. The PLSR models indicated lower PGR expression was associated with <i>G. vaginalis,</i> and higher PGR expression was associated with <i>Lactobacillus </i>species. Cytosine, guanine, and tyrosine were among metabolites significantly associated with higher PGR expression and experimentally determined to be produced by <i>Lactobacillus</i> species. Conversely, citrulline and succinate were associated with lower PGR expression and experimentally determined to be produced by <i>G. vaginalis</i>. The models indicated that bacterial metabolic pathways involved in glucose metabolism, such as glucagon signaling and starch and sugar metabolism, may regulate PGR expression. Demographic phenotypes were also considered from the dataset and did not significantly alter the association between the biological explanatory variables and PGR expression. The results indicate that guanine, cytosine, succinate, starch and sucrose metabolism, and glycolysis gluconeogenesis may be regulators of PGR abundance and function. The models suggest vaginal microbiome factors could play a role in gynecological conditions where progesterone signaling is suppressed. Future experimental work is needed to validate the results of these models and support their use as predictive tools to understand the role of the vaginal microbiome.</p>

Assisted reproductive technologies, such as estrus synchronization and embryo transfer, can aid producers in improving genetics by increasing the number of progeny produced from elite females. The success of embryo transfer is dependent on a viable, competent embryo and a recipient with a receptive uterine environment. Follicular development and luteinization are pertinent for the recipient to establish a functional corpus luteum (CL) that can produce adequate concentrations of progesterone (P4) and provide a uterine environment conducive for the establishment of pregnancy. The objective of this study was to determine if exogenous follicle stimulating hormone (FSH), would increase the number of CL, size and blood perfusion of the largest CL, as well as circulatory concentrations of P4.

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<p>Sex steroids are critical for the post-natal development of the female reproductive system, and are involved in ovulatory cycling and pregnancy. In mice, <em>Mus musculus</em>, female development, cycling, and pregnancy can be affected by the urine of conspecifics, which is known to contain active steroids. Specifically, puberty can be accelerated (the Vandenbergh effect), estrous cycling can be prolonged (the Lee-Boot effect) or synchronized (the Whitten effect), and blastocyst implantation can be disrupted (the Bruce effect). Since steroids alone can affect females in ways that are indistinguishable from these social reproductive effects, I hypothesized that urinary steroids of conspecifics may be absorbed by females, arrive in the reproductive system, and thereby affect females through known mechanisms. First I showed that tritium-labelled 17β-estradiol (³H-E₂) injected into males is excreted in their urine, and that application of urine from these males to the nose of an inseminated female results in detectable levels in her uterus. When I paired inseminated females with non-sire males injected with ³H-E₂, radioactivity was detected in the brain and reproductive tissues of the females. This was the first demonstration of steroids from one animal directly entering the body of another. Similar results were found when I exposed juvenile females to adult males injected with ³H-E₂, and when I exposed nulliparous adult females to same-strain ³H‑E₂- or ³H-progesterone- (³H-P₄) treated adult males or females. Taken with the existing literature, these results suggest that steroid transfer may underlie various social reproductive phenomena in mice, with potential implications for many other species.</p> / Doctor of Philosophy (PhD)