Sellmer Ramos, I. | bioRxiv Science

bioRxiv2025

Short- and long-term effects of uterine disease on oocyte developmental capacity in postpartum dairy cows

The hypothesis was that early postpartum uterine disease would reduce the developmental capacity of oocytes thus contributing to the reduced fertility of dairy cows with uterine disease. Dairy cows were diagnosed healthy or with metritis at 7 to 10 d postpartum. The reproductive tract was collected at approximately 1 mo (Exp. 1) or approximately 80 or 165 d (Exp. 2) postpartum for the collection of cumulus-oocyte complexes (COC). The COC were matured, co- incubated with sperm for fertilization, and cultured to the blastocyst stage (8 d) in vitro. For Exp.1, the disease diagnosis (healthy or metritis) did not affect the number of collected COC or the subsequent embryo development to the blastocyst stage. The presence of purulent material in the uterine lumen (endometritis) at time of oocyte collection, however, was associated with a reduced cleavage rate evaluated 3 d following fertilization. For Exp. 2, there was no effect of disease diagnosis (healthy or metritis) on the number of COC or their subsequent development. Reduced cleavage rates were observed in COC retrieved from cows slaughtered at 80 d postpartum, but not at 165 d postpartum, and this reduction was associated with a vaginal microbiome indicative of uterine disease at 4 to 5 wk postpartum. Regression analyses that included plasma haptoglobin or energy metabolite concentrations or uterine bacterial genera abundance did not explain a large percentage of the variation in oocyte development in vitro. We conclude that there is an effect of uterine disease at one month postpartum on the oocyte and its capacity for development (Exp. 1) and this effect may be present at 80 d postpartum (Exp. 2). In later postpartum cows (165 d postpartum; Exp. 2) there was no effect of uterine disease on in vitro oocyte development. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/636469v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@7ab5d7org.highwire.dtl.DTLVardef@3845e3org.highwire.dtl.DTLVardef@743f52org.highwire.dtl.DTLVardef@1e95c38_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSO_LIOocytes collected at 1 month postpartum from dairy cows with endometritis (purulent uterine lumen) had a lower cleavage rate following in vitro fertilization when compared with oocytes collected from healthy cows (Exp. 1). C_LIO_LIOocytes collected at approximately 80 d postpartum from dairy cows with evidence of uterine disease at 4 to 5 wk postpartum had a lower cleavage rate following in vitro fertilization but this disease-associated difference was not observed when oocytes were collected from cows later postpartum (approximately 165 d postpartum; Exp. 2). C_LIO_LIRegardless of the study (Exp. 1 or 2), uterine disease primarily affected the percentage of oocytes that cleaved after fertilization. C_LIO_LIStatistical associations between circulating metabolites or relative abundance of uterine bacteria were either not significant or explained only a small percentage of the variation in the in vitro embryo development in either experiment. C_LI

physiology↗

bioRxiv2024

Adenomyosis and fibrosis define the morphological memory of the postpartum uterus of dairy cows previously exposed to metritis.

Optimal reproductive success following parturition in lactating dairy cows is dependent upon adequate completion of uterine involution. Failure to resolve pathogenic bacterial contamination within the first week postpartum can lead to uterine disease (metritis). Metritis is associated with decreased fertility and a failure or delay to establish pregnancy. We hypothesized that the inflammation resulting from early postpartum metritis would be associated with long-term changes in uterine morphology due to impaired uterine involution within the first 30 days postpartum (dpp). First parity Holstein cows were diagnosed with or without metritis at 7-10 dpp and uterine tissue were analyzed at 30 (Exp. 1), or 80 and 165 (Exp. 2) dpp for the presence of abnormal morphology, including abnormal invasion of endometrial glands and stroma into the myometrium (adenomyosis) using immunohistochemistry for FOXA2 (uterine gland specific marker) and presence of late postpartum endometrial fibrosis using masons trichrome stain (MTS). Severity of adenomyosis was determined by the number and size of adenomyotic foci, distance of foci from the endometrium-myometrium interface (EMI), and degree of fibrosis (MTS stain intensity). The presence, size, and distance from the EMI of adenomyotic foci were greater later postpartum and in cows with early postpartum diagnosis of metritis. Endometrial fibrosis was greater at the stratum basalis (at EMI) compared to the stratum compactum endometrium (near lumen) for all Exp. 2 cows, but greater endometrial fibrosis (regardless of endometrial region) was observed in cows that were diagnosed with metritis. Taken together, these data indicate that early postpartum metritis is associated with long-term modifications to the postpartum uterine morphology, including aberrant endometrial invasion into the myometrium (adenomyosis) and increased pathological fibrogenesis, leading to the presence of late postpartum endometrial fibrosis (scar tissue). Additionally, increased collagen fiber at the EMI suggests a correlation between the development of adenomyosis and fibrosis, which could possibly result from sustained endometrial inflammation caused by uterine disease.

pathology↗