Summary. The manner whereby progesterone acts as an inhibitor of cleavage of mammalian ova was studied using rabbit ova in vitro. Progesterone blocked cleavage when it was present in the culture medium at concentrations of 10 µg/ml more, and exerted this same effect on all stages up to the morula. The growth of blastocysts was not affected. The action was reversible: ova resumed cleavage within 2 to 3 hr after removal to progesterone-free media. The reversal was time-specific and was used to phase the subsequent cleavage of ova inhibited for varying periods of time. The inhibition was overcome by increasing the concentrations of amino acids or of the serum component in the medium. Supplementing the progesterone media with oestradiol did not reverse the inhibition. Autoradiographs of sections of ova that were kept in C-labelled progesterone for 8 hr, showed silver grains concentrated on the surface of the ovum and the zona pellucida. It is concluded that progesterone blocks cleavage by limiting the supply of protein or amino acids and thus inhibiting protein synthesis within the ovum. Presumably this is done by the progesterone aggregating on the surface of the cell or its protective coating. The inhibitory action appears to be timed in relation to some event that precedes mitosis by an hour or two. It is therefore suggested that the protein synthesis involved is related to formation of the mitotic apparatus or to chromosome condensation.
progesterone cleavage inhibitor rabbit ova in vitro, Daniel Levy progesterone ovum cleavage inhibition 1964, progesterone blocks cell division mammalian embryo, progesterone protein synthesis inhibition embryo development, progesterone zona pellucida surface aggregation, reversible cleavage inhibition progesterone embryo culture, progesterone amino acid limitation ovum cleavage, progesterone mitotic apparatus formation inhibition, rabbit embryo in vitro progesterone morula blastocyst, autoradiograph C-labeled progesterone ovum surface
PMID 14180725 14180725 DOI 10.1530/jrf.0.0070323 10.1530/jrf.0.0070323 Daniel Jr et al. 1964, Daniel Jr 1964
Cite this article
Daniel, J. C., & Levy, J. D. (1964). Action of progesterone as a cleavage inhibitor of rabbit ova in vitro. Journal of reproduction and fertility, 7(3), 323-329. https://doi.org/10.1530/jrf.0.0070323
Daniel JC, Levy JD. Action of progesterone as a cleavage inhibitor of rabbit ova in vitro. J Reprod Fertil. 1964;7(3):323-329. doi:10.1530/jrf.0.0070323
Daniel, Joseph C., and Jack D. Levy. "Action of progesterone as a cleavage inhibitor of rabbit ova in vitro." Journal of reproduction and fertility, vol. 7, no. 3, 1964, pp. 323-329.
Intrauterine pressure was monitored in vivo in oestrogen-treated ovariectomized ewes before, during and after treatment with progesterone (50 mg s.c./day for 3 days). Progesterone reversibly reduced the frequency and amplitude of myometrial activity and abolished uterine reactivity to oxytocin (i.v.) and PGF-2alpha (intrauterine infusion). The rate of rise of intrauterine pressure during active pressure cycles was significantly reduced. These results confirm that the action of progesterone on the ovine myometrium is comparable to the classic progesterone 'block'. The intrauterine infusion of PGF-2alpha (10 microgram/min), which elicited a marked mechanical response in the control animals, failed to stimulate the progesterone-'blocked' uterus, suggesting that the inhibition produced by progesterone is due to a direct action of the hormone on the uterine muscle and not to an indirect mechanism operating through endometrial prostaglandin output.
Santos da Silva A et al., 2026·Reproduction (Cambridge, England)
Endometriosis is an estrogen-dependent inflammatory disorder frequently associated with infertility and characterized by progesterone resistance and impaired endometrial receptivity. While ectopic lesions define the disease, accumulating evidence indicates that molecular abnormalities within the eutopic endometrium substantially contribute to infertility. In this study, we performed transcriptomic analysis of proliferative-phase eutopic endometrium from women with and without endometriosis and identified 44 dysregulated genes, including 13 upregulated and 31 downregulated genes, in women with endometriosis compared with controls. Among the significantly altered genes, YWHAZ (14-3-3 zeta) emerged as a prominently downregulated gene. Reduced YWHAZ expression was further validated at the protein level in both epithelial and stromal compartments of the endometrium from women with endometriosis. To investigate its physiological regulation, we examined YWHAZ expression during early pregnancy in mice and observed a dynamic, stage-specific pattern during the peri-implantation period, with strong expression at gestational days 3.5 and 4.5 and robust expression at the primary decidual zone at gestational day 5.5. Notably, YWHAZ expression was nearly abolished in uteri from progesterone receptor knockout and uterine signal transducer and activator of transcription 3 conditional knockout (Pgrcre/+Stat3f/f) mice, indicating that YWHAZ is dependent on intact progesterone receptor and STAT3 signaling. Together, these findings identify YWHAZ as a hormonally and transcriptionally regulated endometrial factor that is disrupted in endometriosis and tightly linked to implantation and decidual progression. This study highlights YWHAZ as a potential molecular node connecting progesterone resistance and STAT3 dysregulation to defective endometrial function and infertility in endometriosis.
reproductive-endocrinology/ovarian-hormones/progesteronemenstrual-cycle/cycle-disorders/ovulatory-disturbancespcos/pathophysiology/ovarian-morphology
Open Access
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age, typically characterized by irregular menstrual cycles. Our study found that postpartum menstrual cycles were largely restored in PCOS patients following assisted reproductive technology (ART) therapy. However, this recovery in menstrual cycles was not associated with any specific ART procedures. Using a PCOS mouse model, we demonstrated that elevated progesterone levels during pregnancy were responsible for normalizing estrous cyclicity. Elevated levels of progesterone induce granulosa cell apoptosis and deplete large follicles, which potentially contribute to ovarian function suppression during pregnancy. Mechanistic studies indicated that progesterone decreased follicle-stimulating hormone receptor (FSHR) expression in a GATA binding protein 2 (GATA2)-dependent manner. Interestingly, the capacity of granulosa cells to convert androgens to estrogens significantly increased after progesterone withdrawal, as evidenced by elevated cytochrome P450 family 19 subfamily A member 1 (Cyp19a1) expression in granulosa cells when stimulated with FSH. Additionally, we found that progesterone administration reduced the thickness of the uterine endometrium in PCOS mice. Our findings suggest that sustained high levels of progesterone during pregnancy can enhance ovarian reproductive endocrine capacity and improve endometrial function, thereby facilitating the recovery of postpartum menstrual cycles.
To identify preconception clinical and multi-omics factors associated with conception and early pregnancy loss in women with unexplained recurrent pregnancy loss (URPL). In this prospective cohort study, 149 women with URPL selected from 420 outpatients based on guideline-recommended criteria were enrolled between November 2024 and May 2025 and followed-up for 12 months. Preconception fasting plasma was analyzed for clinical biomarkers, untargeted metabolomics, and data-independent acquisition proteomics. Outcomes included conception, ongoing pregnancy beyond 12 weeks and early pregnancy loss before 12 weeks. Multivariable logistic regression was used to evaluate the associations of clinical and multi-omics factors with reproductive outcomes, adjusting for maternal age, body mass index, number of prior losses, and use of assisted reproductive technology. Of 149 women, 99 conceived (66.4%) during the follow-up. By 12 weeks of gestation, 67 (67.7%) had ongoing pregnancies and 32 (32.3%) experienced early pregnancy loss. Higher testosterone was associated with lower probability of conception (adjusted odds ratio [aOR] 0.50, 95% confidence interval [CI] 0.28-0.89, p = 0.019). Women who conceived showed higher levels of progesterone-related metabolites, including 17-hydroxyprogesterone (fold change, FC = 3.89), pregnanediol 3-O-glucuronide (FC = 2.37), and pregnanetriol 3α-O-β-D-glucuronide (FC = 2.39). Among women who conceived, higher prolactin was associated with higher odds of early pregnancy loss (aOR 1.09, 95% CI 1.01-1.18, p = 0.036), and anti-phosphatidylserine/prothrombin showed a borderline association (aOR 1.07, 95% CI 1.00-1.14, p = 0.052). Early pregnancy loss was characterized by lower bile acid-related metabolites and higher caffeine and methylxanthine metabolites. Proteomic analysis showed enrichment of bile acid biosynthetic process. After adjustment, higher 7α,12α-dihydroxy-3-oxocholest-4-en-27-oic acid was associated with lower odds of early pregnancy loss (aOR 0.64, 95% CI 0.44-0.95, p = 0.025). Higher testosterone was associated with lower odds of conception. Among women who conceived, early pregnancy loss was associated with higher prolactin, borderline higher anti-PS/PT, lower bile acid-related metabolites, and higher caffeine-related metabolites, with 7α,12α-dihydroxy-3-oxocholest-4-en-27-oic acid identified as an exploratory metabolomic candidate. These findings suggest that potential androgen-related biology, prolactin, non-criteria antiphospholipid antibodies, and bile acid metabolism may be associated with reproductive outcomes in URPL, warranting validation in independent cohorts.