Local Regulatory Changes of HSD11B1 and NR3C1 in the Follicular and Luteal Tissue During Experimentally Induced Ovulation in the Cow.

The objective of the study was to characterise the expression patterns of the two key components of cortisol action namely HSD11B1 (11-beta-hydroxysteroid dehydrogenase type 1) and NR3C1 (nuclear receptor subfamily 3, group C, member 1, also known as the glucocorticoid receptor) in superovulation induced bovine follicles during the periovulation and subsequent corpus luteum (CL) formation. Bovine ovaries containing preovulatory follicles or CL were timely defined during induced ovulation as follows: 0 h before GnRH (Gonadotropin-releasing hormone) application, and 4, 10, 20, 25 (follicles) and 60 h (early CL) after GnRH. The low mRNA expression of HSD11B1 and NR3C1 in the follicle group before the GnRH application increased significantly in the follicle group 20 h after GnRH and remained high afterward also in the early CL group. In contrast, the high NR3C1 mRNA decreased in follicles 25 h after GnRH (close to ovulation) and significantly increased again after ovulation (early CL). Our results indicated the involvement of HSD11B1 and NR3C1 as the two key components of cortisol action in the local mechanisms coordinating final follicle maturation, ovulation, follicular-luteal transition and CL development in the cow.

Genetic regulation of ovulation rate and multiple births.

Ovulation rate in many mammalian species is controlled to regulate the numbers of offspring and maximise reproductive success. Pathways that regulate ovulation rate still respond to genetic and environmental factors and show considerable variation within and between species. Genetic segregation, positional cloning, and association studies have discovered numerous mutations and genetic risk factors that contribute to this variation. Notable among the discoveries has been the role of mutations in bone morphogenetic protein 15 (BMP15 ), growth differentiation factor 9 (GDF9 ) and bone morphogenetic protein receptor type 1B (BMPR1B ) from the intra-ovarian signalling pathway contributing to the evidence that signalling from the oocyte is the key driver in follicle regulation rather than circulating gonadotrophin concentrations. Multiple variants in different domains of BMP15 and GDF9 result in partial or complete loss of function of the proteins providing insights into their functional roles and differential regulation contributing to species differences in ovulation rate. Early success encouraged many more studies in prolific strains of sheep, cattle and goats providing a valuable catalogue of genetic variants of large effect increasing ovulation rate and litter size. More recently, genetic association studies are beginning to identify genetic risk factors with smaller effects. Most genes implicated are from pathways with defined roles in regulation of the ovarian function. However, some genomic regions suggest regulation by novel genes. Continuing genetic and related functional studies will add further to our understanding of the detailed regulation of ovulation rate and litter size with implications for health and animal production systems.

Multimodal sexual signals are not precise indicators of fertility in female Kinda baboons.

Female fertility signals are found across taxa, and the precision of such signals may be influenced by the relative strength of different sexual selection mechanisms. Among primates, more precise signals may be found in species with stronger direct male-male competition and indirect female mate choice, and less precise signals in species with stronger indirect male-male competition (e.g. sperm competition) and direct female mate choice. We tested this hypothesis in a wild population of Kinda baboons in Zambia, combining data on female signals with reproductive hormones (estrogen and progesterone metabolites) and intra- and inter-cycle fertility. We predicted that Kinda baboons will exhibit less precise fertility signals than other baboon species, as they experience weaker direct and stronger indirect male-male competition. The frequency of copulation calls and proceptive behavior did not vary with hormones or intra- or inter-cycle fertility in almost all models. Sexual swelling size was predicted by the ratio of estrogen to progesterone metabolites, and was largest in the fertile phase, but differences in size across days were small. Additionally, there was variability in the timing of ovulation relative to the day of sexual swelling detumescence across cycles and swelling size did not vary with inter-cycle fertility. Our results suggest that female Kinda baboon sexual swellings are less precise indicators of fertility compared to other baboon species, while signals in other modalities do not reflect variation in intra- and inter-cycle fertility. Female Kinda baboon sexual signals may have evolved as a strategy to reduce male monopolizability, allowing for more female control over reproduction by direct mate choice.

Actomyosin contraction in the follicular epithelium provides the major mechanical force for follicle rupture during Drosophila ovulation.

Ovulation is critical for sexual reproduction and consists of the process of liberating fertilizable oocytes from their somatic follicle capsules, also known as follicle rupture. The mechanical force for oocyte expulsion is largely unknown in many species. Our previous work demonstrated that Drosophila ovulation, as in mammals, requires the proteolytic degradation of the posterior follicle wall and follicle rupture to release the mature oocyte from a layer of somatic follicle cells. Here, we identified actomyosin contraction in somatic follicle cells as the major mechanical force for follicle rupture. Filamentous actin (F-actin) and nonmuscle myosin II (NMII) are highly enriched in the cortex of follicle cells upon stimulation with octopamine (OA), a monoamine critical for Drosophila ovulation. Pharmacological disruption of F-actin polymerization prevented follicle rupture without interfering with the follicle wall breakdown. In addition, we demonstrated that OA induces Rho1 guanosine triphosphate (GTP)ase activation in the follicle cell cortex, which activates Ras homolog (Rho) kinase to promote actomyosin contraction and follicle rupture. All these results led us to conclude that OA signaling induces actomyosin cortex enrichment and contractility, which generates the mechanical force for follicle rupture during Drosophila ovulation. Due to the conserved nature of actomyosin contraction, this work could shed light on the mechanical force required for follicle rupture in other species including humans.

Participation of preovulatory follicles in the activation of primordial follicles in mouse ovaries.

The mechanisms behind the selection and initial recruitment of primordial follicles (PmFs) from the non-growing PmF pool during each estrous cycle in females remain largely unknown. This study demonstrates that PmFs closest to the ovulatory follicle are preferentially activated in mouse ovaries under physiological conditions. PmFs located within 40 µm of the ovulatory follicles were more likely to be activated compared to those situated further away during the peri-ovulation period. Repeated superovulation treatments accelerated the depletion of the PmF reserve, whereas continuous suppression of ovulation delayed PmF reserve consumption. Spatial transcriptome sequencing of peri-ovulatory follicles revealed that ovulation primarily induces the degradation and remodeling of the extracellular matrix (ECM). This ECM degradation reduces mechanical stress around PmFs, thereby triggering their activation. Specifically, Cathepsin L (CTSL), a cysteine proteinase and lysosomal enzyme involved in ECM degradation, initiates the activation of PmFs adjacent to ovulatory follicles in a distance-dependent manner. These findings highlight the link between ovulation and selective PmF activation, and underscore the role of CTSL in this process under physiological conditions.

Is it possible to replace eCG by GnRH in the hormonal protocol for timed artificial insemination in ewes during the breeding season?

Hormonal protocols based on progestogens and equine chorionic gonadotrophin (eCG) are efficient for estrus and ovulation synchronization in ewes. Although eCG is indispensable during seasonal anestrus, it may not be necessary during the breeding season. Thus, we tested the hypothesis that GnRH is effective in replacing eCG during the breeding season allowing satisfactory ovulation rate, luteal function and conception rates after timed artificial insemination (TAI). Ewes (n = 134) with a minimum body condition score of 2.5 (0-5 scale) were treated with intravaginal devices (IVD) containing 60 mg of medroxyprogesterone acetate (MPA) for seven days and received 0.26 mg of sodium cloprostenol at the time of IVD removal. In Exp. 1, at IVD removal, ewes (n = 29) were allocated to three groups: eCG (200 IU at IVD removal; n = 10); eCG+GnRH (200 IU eCG at IVD removal and 4 µg of buserelin 36 h later; n = 10); or GnRH (buserelin 36 h after IVD removal; n = 9). Blood samples were collected 2, 6 and 12 days after TAI moment (54 h after IVD removal), for progesterone (P4) analysis. In Exp 2, the ewes were allocated to eCG (n = 10) or GnRH (n = 10) groups, as above described, and ovulation moment was evaluated 54, 66 and 78 h after IVD removal. In Exp 3, TAI was performed in ewes from eCG (n = 45) and GnRH (n = 40) groups using 100 × 106 motile spermatozoa from a pool of semen collected from four rams. In Exp. 1, based on P4 levels, we confirmed that all the ewes ovulated (29/29) and there was no significant effect of group (P = 0.89) or group x day (P = 0.18) on P4 concentration, being observed a significant effect of day (P = 0.0001). In Exp. 2, the maximum DF diameter (P = 0.26) and ovulation moment (P = 0.69) did not differ between groups. In Exp. 3, pregnancy rate was significantly lower (P = 0.02) in GnRH (22.5 %; 9/40) compared to eCG (46.7 %; 21/45). The results indicate that, although ovulation and luteal function were not altered after eCG, eCG+GnRH or GnRH treatment, GnRH alone before TAI cannot be used to replace eCG treatment during the breeding season.

Cervix-Deep Rectal Temperature Differential on the Day of Ovulation is Correlated With Embryo Recovery Results in Mares.

Variations in temperature throughout the reproductive tract have been noted in many species. A recent study found the cervix-rectum temperature differential (CR-TD) in cattle was related to fertility. The present study aimed to assess the CR-TD in mares around the time of ovulation and relate it to embryo recover. Over 52 cycles, mares were inseminated with a fertile stallion and embryo recovery was undertaken on Day 7 post ovulation. Further 10 control mares were not inseminated. Rectal and cervical temperatures were measured using a precision thermometer on four or five occasions: the day of deslorelin administration and insemination, the day before ovulation, the day of ovulation (Day 0), the day after ovulation and, for inseminated mares, before embryo recovery on Day 7. One-way ANOVA showed that the CR-TD was significantly lower on the day of ovulation in the 36 positive cycles, in which an embryo was recovered, versus the 16 in which the embryo flush was negative (0.21 ± 0.17 vs. 0.40 ± 0.09°C; p < 0.001). Control cycles showed equivalent CR-TD to positive (0.13 ± 0.22 vs. 0.21 ± 0.17°C; p = 0.196) but not negative cycles (0.13 ± 0.22 vs. 0.40 ± 0.09°C; p < 0.001). A positive embryo recovery was associated with lower CR-TDs from the time of insemination and deslorelin to the day after ovulation compared to the day of embryo flushing (RM ANOVA; p < 0.001; Pairwise comparisons; p ≤ 0.01, in all cases). Rectal or cervical temperatures per se showed no significant differences between positive, negative or control cycles at any time point. In conclusion, a thermoregulatory process occurs close to ovulation which results in a lower CR-TD in cycles that produced an embryo versus those which did not. Further characterisation of TDs within the reproductive tract of the mare would increase our understanding of the conditions required for optimum fertility.

Comparison of Day-Specific Serum LH, Estradiol, and Progesterone with MiraTM Monitor Urinary LH, Estrone-3-glucuronide, and Pregnanediol-3-glucuronide Levels in Ovulatory Cycles.

Background and Objectives: Fertility tracking apps and devices are now currently available, but urinary hormone levels lack accuracy and sensitivity in timing the start of the 6-day fertile window and the precise 24 h interval of transition from ovulation to the luteal phase. We hypothesized the serum hormones estradiol (E2) and progesterone (P) might be better biomarkers for these major ovulatory cycle events, using appropriate mathematical tools. Materials and Methods: Four women provided daily blood samples for serum E2, P, and LH (luteinizing hormone) levels throughout their entire ovulatory cycles, which were indexed to the first day of dominant follicle (DF) collapse (defined as Day 0) determined by transvaginal sonography; therefore, ovulation occurred in the 24 h interval of Day -1 (last day of maximum diameter DF) to Day 0. For comparison, a MiraTM fertility monitor was used to measure daily morning urinary LH (ULH), estrone-3-glucuronide (E3G), and pregnanediol-3-glucuronide (PDG) levels in three of these cycles. Results: There were more fluctuations in the MiraTM hormone levels compared to the serum levels. Previously described methods, the Fertility Indicator Equation (FIE) and Area Under the Curve (AUC) algorithm, were tested for identifying the start of the fertile window and the ovulation/luteal transition point using the day-specific hormone levels. The FIE with E2 levels predicted the start of the 6-day fertile window on Day -7 (two cycles) and Day -5 (two cycles), whereas no identifying signal was found with E3G. However, both pairs of (E2, P) and (E3G, PDG) levels with the AUC algorithm signaled the Day -1 to Day 0 ovulation/luteal transition interval in all cycles. Conclusions: serum E2 and (E2, P) were better biomarkers for signaling the start of the 6-day fertile window, but both MiraTM and serum hormone levels were successful in timing the [Day -1, Day 0] ovulatory/luteal transition interval. These results can presently be applied to urinary hormone monitors for fertility tracking and have implications for the direction of future fertility tracking technology.

Direct and carry-over effect of grassland herbage allowance on metabolic hormones and reproduction in primiparous beef cows undergoing temporary weaning and flushing.

Grazing management significantly contributes to low beef production in cow-calf systems within the Rio de la Plata native grasslands. An herbage allowance (HA) of 4 kg DM/kg BW increased the productive response of primiparous cows grazing shallow soils compared to 2.5. However, the impact of HA on metabolic changes and its association with productive response were not studied. We studied two levels of native grassland HA from -150 days relative to calving (DC) to weaning (195 DC) in spring-calving primiparous beef cows undergoing temporary weaning (TW) and flushing at 86 ±â€¯12 DC on herbage intake (HI), body condition score (BCS), BW, milk yield, calf weight, concentrations of metabolic hormones, and the probability of ovulation and pregnancy. Thirty-one heifers were assigned to HA treatments that fluctuated throughout seasons: autumn (-150 to -90 DC) at 5 and 3 kg DM/kg BW, winter (-90 to 0 DC) at 3 and 3 kg DM/kg BW, and spring-summer (0 to 195 DC) at 4 and 2 kg DM/kg BW for High and Low HA, respectively. Data were analysed using linear models and generalised linear models for continuous and categorical variables, respectively. During the autumn period, HI, insulin, IGF-I, BCS, and BW were higher in High HA than Low, despite small differences in herbage mass between HA. Throughout the winter, spring, and summer, HI, insulin, leptin, and BCS changes did not differ between HA. However, IGF-I concentrations were greater at -65 and -40 DC (84 vs 55 ±â€¯8.6 ng/mL; P < 0.05) and tended to be greater after TW in High HA than Low. The probability of ovulation did not reach significance (0.94 vs 0.75 ±â€¯0.11 for High and Low HA, respectively; P = 0.125), while the probability of pregnancy was greater in High HA than in Low HA (0.9 vs 0.61 ±â€¯0.10; P = 0.07). Ovulation probability exhibited a positive association with IGF-I concentrations at -90 and -40 DC (P < 0.05), but not postpartum. Milk yield did not differ between treatments, while calf weight was heavier at weaning in High HA cows (194 vs 178 ±â€¯3.3 kg; P < 0.05). High HA enhances autumn HI and BCS and generates a carry-over effect on IGF-I concentrations throughout winter and after TW ("metabolic memory"), explaining the better reproductive response. Moderate changes in cows' nutrition during autumn contribute to changes in metabolic status and reproductive outcomes in primiparous cows grazing moderate herbage production native grasslands.

Spontaneous ovulation in the cat: incidence among queens presented at a veterinary teaching facility.

OBJECTIVES: The queen is recognised as an induced ovulator. Ovulation without male contact is generally regarded as spontaneous. The aim of this study was to provide an estimate of the incidence of spontaneous ovulation in a population of intact queens presented to a veterinary care facility for both reproductive and non-reproductive reasons. The secondary objective was to determine the roles of age, breed, body weight, presence of tom cats or other cycling queens, and physical contact with humans on triggering spontaneous ovulation, along with its implications. METHODS: Serum samples from post-pubertal intact queens presented between January 2020 and June 2023 to the Veterinary Teaching Hospital of the University of Padova, Italy, were retrieved and assayed for progesterone (P4) levels. Serum P4 above 2.0 ng/ml without a history of male contact was considered as proof of spontaneous ovulation. RESULTS: In total, 31 serum samples from 29 intact post-pubertal queens were obtained. Of the 31 samples, 14 had a P4 concentration above 2.0 ng/ml and 9/29 (31.0%) queens ovulated spontaneously. The mean age and weight of the nine spontaneously ovulating queens were 4.3 ± 5.7 years and 3.7 ± 0.8 kg, respectively. One queen ovulated spontaneously at her first heat at 6 months of age, which makes it the earliest spontaneous ovulation reported. CONCLUSIONS AND RELEVANCE: As both our findings and previous publications indicate that the incidence of spontaneous ovulation in queens is consistently ⩾30%, cats should not be considered strictly induced ovulators, but as a species in which ovulation can be either spontaneous or induced. Since the risk of progesterone-dependent conditions (cystic endometrial hyperplasia - pyometra complex, feline mammary hypertrophy) is increased in these queens, veterinarians should be aware and advise breeders and clients accordingly.

Female cats ovulate upon vaginal stimulation exerted by the spikes of the male's penis while mating, which makes them induced ovulators. When ovulation occurs without male contact, it is considered spontaneous. There are several factors that are thought to facilitate this non-induced ovulation, but no consensus on their relevance. The aim of this study was to provide an estimate of the rate of spontaneous ovulation in a population of intact female cats of various breeds presented to a veterinary care facility, as well as the influence of factors such as age, breed, body weight, presence of male cats or other cycling females, and physical contact with humans on triggering spontaneous ovulation. In addition, possible implications arising from progesterone exposure were assessed.Progesterone was retrospectively assayed in the serum of adult cycling female cats presented to the Veterinary Teaching Hospital of the University of Padova, Italy, between January 2020 and June 2023. Values above 2.0 ng/ml without a history of male contact were considered proof of spontaneous ovulation. Out of 29 cats, nine (31%) ovulated spontaneously, with one female having done so at puberty (6 months of age), which makes it the first spontaneous ovulation ever reported in a pubertal queen.As spontaneous ovulation has been found to occur at a rate of more than 30% both in our and in previous publications on this topic, we propose that cats should be considered both an induced and a spontaneously ovulating species. Since animals that ovulate spontaneously, and therefore experience additional luteal phases, are at a higher risk of developing progesterone-dependent conditions, veterinarians should be aware and advise breeders and clients accordingly.

Investigations into the role of platelet-activating factor in the peri-conception period of the mare.

In Brief: In many mammals, the lipid platelet-activating factor (PAF) has important functions in female reproduction and fertility. This study shows that PAF is present in the reproductive tissues of mares and is involved in processes related to ovulation and early pregnancy. Abstract: Platelet-activating factor (PAF) has been implicated in a number of reproductive processes ranging from ovulation to embryo motility but has not been widely explored in the mare. To identify the presence and examine the role of PAF in the equine periconception processes, targeted mass spectrometry coupled with chromatographic separation was performed on equine follicular fluid (FF), and PAF was quantitatively detected. Subsequently, untargeted high-resolution mass spectrometry-based lipidomic analysis was carried out to quantify PAF in different-sized pre-ovulatory follicles, whereby different molecular species of PAF, PAF (14:0) and PAF (16:1), were both seen to be increasing with follicle diameter. These findings suggest that PAF within FF is increasing as preovulatory follicles approach ovulation. Additionally, immunofluorescence staining identified the PAF receptor in the luminal pericellular, apical, and basal aspect of equine oviductal epithelial cells. Lastly, an equine oviductal epithelial organoid model was generated and showed that the addition of PAF significantly increased the ciliary beat frequency (CBF) (Hz), an action consistent with a role for PAF in embryo migration. It is proposed that the local action of PAF on the ciliated cells of the oviduct propels both the oocyte and the conceptus towards the uterus. In the mare, it appears that PAF is a contributor during the periconception period, potentially being a mediator in the mechanisms of ovulation and in the dialogue of very early pregnancy.

A double ovulation protocol for Xenopus laevis produces doubled fertilisation yield and moderately transiently elevated corticosterone levels without loss of egg quality.

The African claw-toed frog, Xenopus laevis, is a well-established laboratory model for the biology of vertebrate oogenesis, fertilisation, and development at embryonic, larval, and metamorphic stages. For ovulation, X. laevis females are usually injected with chorionic gonadotropin, whereupon they lay typically hundreds to thousands of eggs in a day. After being rested for a minimum of three months, animals are re-used. The literature suggests that adult females can lay much larger numbers of eggs in a short period. Here, we compared the standard "single ovulation" protocol with a "double ovulation" protocol, in which females were ovulated, then re-ovulated after seven days and then rested for three months before re-use. We quantified egg number, fertilisation rate (development to cleavage stage), and corticosterone secretion rate as a measure of stress response for the two protocol groups over seven 3-month cycles. We found no differences in egg number-per-ovulation or egg quality between the groups and no long-term changes in any measures over the 21-month trial period. Corticosterone secretion was elevated by ovulation, similarly for the single ovulation as for the first ovulation in the double-ovulation protocol, but more highly for the second ovulation (to a level comparable to that seen following shipment) in the latter. However, both groups exhibited the same baseline secretion rates by the time of the subsequent cycle. Double ovulation is thus transiently more stressful/demanding than single ovulation but within the levels routinely experienced by laboratory X. laevis. Noting that "stress hormone" corticosterone/cortisol secretion is linked to physiological processes, such as ovulation, that are not necessarily harmful to the individual, we suggest that the benefits of a doubling in egg yield-per-cycle per animal without loss of egg quality or signs of acute or long-term harm may outweigh the relatively modest and transient corticosterone elevation we observed. The double ovulation protocol therefore represents a potential new standard practice for promoting the "3Rs" (animal use reduction, refinement and replacement) mission for Xenopus research.

Effect of the gonadotropin surge on steroid receptor regulation in preovulatory follicles and newly formed corpora lutea in the cow.

The objective of the study was to characterize the mRNA expression patterns of specific steroid hormone receptors namely, estrogen receptors (ESRRA-estrogen related receptor alpha and ESRRB-estrogen related receptor beta) and progesterone receptors (PGR) in superovulation-induced bovine follicles during the periovulation and subsequent corpus luteum (CL) formation. The bovine ovaries (n = 5 cow / group), containing preovulatory follicles or early CL, were collected relative to injection of the gonadotropin-releasing hormone (GnRH) at (I) 0 h, (II) 4 h, (III) 10 h, (IV) 20 h, (V) 25 h (preovulatory follicles) and (VI) 60 h (CL, 2-3 days after induced ovulation). In this experiment, we analyzed the steroid receptor mRNA expression and their localization in the follicle and CL tissue. The high mRNA expression of ESRRA, ESRRB, and PGR analyzed in the follicles before ovulation is significantly reduced in the group of follicles during ovulation (25 h after GnRH), rising again significantly after ovulation in newly formed CL, only for ESRRA and PGR (P < 0.05). Immunohistochemically, the nuclei of antral follicles' granulosa cells showed a positive staining for ESRRA, followed by higher activity in the large luteal cells just after ovulation (early CL). In contrast, the lower PGR immunopresence in preovulatory follicles increased in both small and large luteal cell nuclei after follicle ovulation. Our results of steroid receptor mRNA expression in this experimentally induced gonadotropin surge provide insight into the molecular mechanisms of the effects of steroid hormones on follicular-luteal tissue in the period close to the ovulation and subsequent CL formation in the cow.

Granulosa Cell-Layer Stiffening Prevents Escape of Mural Granulosa Cells from the Post-Ovulatory Follicle.

Ovulation is vital for successful reproduction. Following ovulation, cumulus cells and oocyte are released, while mural granulosa cells (mGCs) remain sequestered within the post-ovulatory follicle to form the corpus luteum. However, the mechanism underlying the confinement of mGCs has been a longstanding mystery. Here, in vitro and in vivo evidence is provided demonstrating that the stiffening of mGC-layer serves as an evolutionarily conserved mechanism that prevents mGCs from escaping the post-ovulatory follicles. The results from spatial transcriptome analysis and experiments reveal that focal adhesion assembly, triggered by the LH (hCG)-cAMP-PKA-CREB signaling cascade, is necessary for mGC-layer stiffening. Disrupting focal adhesion assembly through RNA interference results in stiffening failure, mGC escape, and the subsequent development of an abnormal corpus luteum characterized by decreased cell density or cavities. These findings introduce a novel concept of "mGC-layer stiffening", shedding light on the mechanism that prevents mGC escape from the post-ovulatory follicle.

History of the Development of Knowledge about the Neuroendocrine Control of Ovulation-Recent Knowledge on the Molecular Background.

The physiology of reproduction has been of interest to researchers for centuries. The purpose of this work is to review the development of our knowledge on the neuroendocrine background of the regulation of ovulation. We first describe the development of the pituitary gland, the structure of the median eminence (ME), the connection between the hypothalamus and the pituitary gland, the ovarian and pituitary hormones involved in ovulation, and the pituitary cell composition. We recall the pioneer physiological and morphological investigations that drove development forward. The description of the supraoptic-paraventricular magnocellular and tuberoinfundibular parvocellular systems and recognizing the role of the hypophysiotropic area were major milestones in understanding the anatomical and physiological basis of reproduction. The discovery of releasing and inhibiting hormones, the significance of pulse and surge generators, the pulsatile secretion of the gonadotropin-releasing hormone (GnRH), and the subsequent pulsatility of luteinizing (LH) and follicle-stimulating hormones (FSH) in the human reproductive physiology were truly transformative. The roles of three critical neuropeptides, kisspeptin (KP), neurokinin B (NKB), and dynorphin (Dy), were also identified. This review also touches on the endocrine background of human infertility and assisted fertilization.

Hormonal and circuit mechanisms controlling female sexual behavior.

Sexual behavior is crucial for reproduction in many animals. In many vertebrates, females exhibit sexual behavior only during a brief period surrounding ovulation. Over the decades, studies have identified the roles of ovarian sex hormones, which peak in levels around the time of ovulation, and the critical brain regions involved in the regulation of female sexual behavior. Modern technical innovations have enabled a deeper understanding of the neural circuit mechanisms controlling this behavior. In this review, I summarize our current knowledge and discuss the neural circuit mechanisms by which female sexual behavior occurs in association with the ovulatory phase of their cycle.

Expression dynamics of adipokines during induced ovulation in the bovine follicles and early corpus luteum.

The study aimed to assess the local gene expression of adipokine members, namely vaspin, adiponectin, visfatin, resistin and their associated receptors - heat shock 70 protein 5 (HSPA5), adiponectin receptor 1 (AdipoR1) and adiponectin receptor 2 (AdipoR2) - in bovine follicles during the preovulatory period and early corpus luteum development. Follicles were collected before gonadotropin-releasing hormone (GnRH) treatment (0 h) and at 4, 10, 20, 25 and 60 h after GnRH application through transvaginal ovariectomy (n = 5 samples/group). Relative mRNA expression levels were quantified using real-time reverse transcription polymerase chain reaction (RT-qPCR). Vaspin exhibited high mRNA levels immediately 4 h after GnRH application, followed by a significant decrease. Adiponectin mRNA levels were elevated at 25 h after GnRH treatment. AdipoR2 exhibited late-stage upregulation, displaying increased expression at 20, 25 and 60 h following GnRH application. Visfatin showed upregulation at 20 h post-GnRH application. In conclusion, the observed changes in adipokine family members within preovulatory follicles, following experimentally induced ovulation, may constitute crucial components of the local mechanisms regulating final follicle growth and development.

Involvement of somatotrophic hormones in the postpartum regulation of ovarian activity in mares.

Mares resume ovarian activity rapidly after foaling. Besides follicle-stimulating hormone (FSH) and luteinizing hormone (LH), the pituitary synthesizes prolactin and growth hormone which stimulate insulin-like growth factor (IGF) synthesis in the liver. We tested the hypothesis that follicular growth is initiated already antepartum, mares with early and delayed ovulation differ in IGF-1 release and that there is an additional IGF-1 synthesis in the placenta. Plasma concentrations of LH, FSH, IGF-1, IGF-2, activin and prolactin. IGF-1, IGF-2, prolactin and their receptors in placental tissues were analyzed at the mRNA and protein level. Follicular growth was determined from 15 days before to 15 days after foaling in 14 pregnancies. Mares ovulating within 15 days postpartum formed group OV (n=5) and mares not ovulating within 15 days group NOV (n=9). Before foaling, follicles with a diameter >1 cm were present in all mares and their number increased over time (p<0.05). Follicle growth after foaling was more pronounced in OV mares (day p<0.001, group p<0.05, day x group p<0.05) in parallel to an increase in LH concentration (p<0.001, day x group p<0.001) while FSH increased (p<0.001) similarly in both groups. Plasma concentrations of IGF-1 and prolactin peaked one day after foaling (p<0.001). The IGF-1 mRNA abundance was higher in the allantochorion but lower in the amnion of OV versus NOV mares (group p=0.01, localization x group p<0.01). The IGF-1 receptor mRNA was most abundant in the allantochorion (p<0.001) and IGF-1 protein was expressed in placental tissue without differences between groups. In conclusion, follicular growth in mares is initiated before foaling and placental IGF-1 may enhance resumption of ovulatory cycles.

Prostaglandin F2α treatment does not hasten ovulation in weaned sows.

This study evaluated the efficiency of prostaglandin F2α (PGF) to hasten ovulation in weaned sows. In experiment I, weaned sows detected in estrus (0 h) received: no hormone (Control; n = 56); 0.5 mg PGF IM at 0 h and 2 h (PGF0; n = 56); or 0.5 mg PGF IM at 24 h and 26 h (PGF24; n = 55). In experiment II, weaned sows that did not express estrus signs until 72 h after weaning (0 h) were assigned to: no hormone (Control; n = 45); 10 µg buserelin acetate IM at 0 h (Buserelin; n = 43); 0.5 mg PGF IM at 34 h and 36 h (PGF; n = 44); or 10 µg buserelin acetate IM at 0 h plus 0.5 mg PGF IM at 34 h and 36 h (Buserelin + PGF; n = 45). In experiment I, no effect of PGF on the interval treatment onset to ovulation was observed (P > 0.05), and no treatment effect was observed on the relative or cumulative proportion of females that ovulated post-treatment onset (P > 0.05). In experiment II, treatment onset to ovulation interval was shorter for Buserelin group than for PGF group (P < 0.05), and a higher cumulative percentage of Buserelin treated sows ovulated up to 48 h compared to PGF and Control groups (P < 0.01), with no differences from Buserelin + PGF. Treatments did not affect total number of piglets born in both experiments (P > 0.05). In conclusion, PGF did not hasten ovulation timing or affect litter size in weaned sows.

Transcriptome analysis of porcine oocytes during postovulatory aging.

Decreased oocyte quality is a significant contributor to the decline in female fertility that accompanies aging in mammals. Oocytes rely on mRNA stores to support their survival and integrity during the protracted period of transcriptional dormancy as they await ovulation. However, the changes in mRNA levels and interactions that occur during porcine oocyte maturation and aging remain unclear. In this study, the mRNA expression profiles of porcine oocytes during the GV, MII, and aging (24 h after the MII stage) stages were explored by transcriptome sequencing to identify the key genes and pathways that affect oocyte maturation and postovulatory aging. The results showed that 10,929 genes were coexpressed in porcine oocytes during the GV stage, MII stage, and aging stage. In addition, 3037 genes were expressed only in the GV stage, 535 genes were expressed only in the MII stage, and 120 genes were expressed only in the aging stage. The correlation index between the GV and MII stages (0.535) was markedly lower than that between the MII and aging stages (0.942). A total of 3237 genes, which included 1408 upregulated and 1829 downregulated genes, were differentially expressed during porcine oocyte postovulatory aging (aging stage vs. MII stage). Key functional genes, including ATP2A1, ATP2A3, ATP2B2, NDUFS1, NDUFA2, NDUFAF3, SREBF1, CYP11A1, CYP3A29, GPx4, CCP110, STMN1, SPC25, Sirt2, SYCP3, Fascin1/2, PFN1, Cofilin, Tmod3, FLNA, LRKK2, CHEK1/2, DDB1/2, DDIT4L, and TONSL, and key molecular pathways, such as the calcium signaling pathway, MAPK signaling pathway, TGF-ß signaling pathway, PI3K/Akt signaling pathway, FoxO signaling pathway, gap junctions, and thermogenesis, were found in abundance during porcine postovulatory aging. These genes are mainly involved in the regulation of many biological processes, such as oxidative stress, calcium homeostasis, mitochondrial function, and lipid peroxidation, during porcine oocyte postovulatory aging. These results contribute to a more in-depth understanding of the biological changes, key regulatory genes and related biological pathways that are involved in oocyte aging and provide a theoretical basis for improving the efficiency of porcine embryo production in vitro and in vivo.