Development Of Reproductive System Research Articles

Differentiation of uniparental human embryonic stem cells into granulosa cells reveals a paternal contribution to gonadal development.

Genomic imprinting underlies the mammalian requirement for sexual reproduction. Nonetheless, the relative contribution of the two parental genomes during human development is not fully understood. Specifically, a fascinating question is whether the formation of the gonad, which holds the ability to reproduce, depends on equal contribution from both parental genomes. Here, we differentiated androgenetic and parthenogenetic human pluripotent stem cells (hPSCs) into ovarian granulosa-like cells (GLCs). We show that in contrast to biparental and androgenetic cells, parthenogenetic hPSCs present a reduced capacity to differentiate into GLCs. We further identify the paternally expressed gene IGF2 as the most upregulated imprinted gene upon differentiation. Remarkably, while IGF2 knockout androgenetic cells fail to differentiate into GLCs, the differentiation of parthenogenetic cells supplemented with IGF2 is partly rescued. Thus, our findings unravel a surprising essentiality of genes that are only expressed from the paternal genome to the development of the female reproductive system.

Changes of Development from Childhood to Late Adulthood in Rats Tracked by Urinary Proteome

To date, studies of development have mainly focused on the embryonic stage and a short time thereafter. There has been little research on the whole life of an individual from childhood to aging and death. For the first time, we used noninvasive urinary proteome technology to track changes in several important developmental time points in a group of rats, covering 10 time points from childhood, adolescence, young adulthood, middle adulthood, and near-death in old age. Similar to previous studies on puberty, proteins were detected and they are involved in sexual or reproductive maturation, mature spermatozoa in seminiferous tubules (first seen), gonadal hormones, decline of estradiol, brain growth, and central nervous system myelination, and our differential protein enrichment pathways also included reproductive system development, tube development, response to hormone, response to estradiol, brain development, and neuron development. Similar to previous studies in young adults, proteins were detected and they are involved in musculoskeletal maturity, peak bone mass, development of the immune system, and growth and physical development, and our differential proteins enrichment pathways also included skeletal system development, bone regeneration, system development, immune system processes, myeloid leukocyte differentiation, and developmental growth. Studies on aging-related changes in neurons and neurogenesis have been reported, and we also found relevant pathways in aged rats, such as regulation of neuronal synaptic plasticity and positive regulation of long-term neuronal synaptic plasticity. However, at all time points throughout life, there were many biological pathways revealed by differential urinary protein enrichment involving multiple organs, tissues, systems, etc. that have not been mentioned in existing studies. This study shows comprehensive and detailed changes in rat lifetime development through the urinary proteome, helping to fill the gap in development research. Moreover, it provides a new approach to monitoring changes in human health and diseases of aging using the urinary proteome.

Clinical сase of disorder of sex development with karyotype 47XYY

Disorder of sex development (DSD) is a term used to refer to congenital disorders that led to atypical structure of the genitals. The cause of DSD is a disorder of the embryonic development of the reproductive system due to chromosomal, genetic pathology or other adverse effects on pregnancy. DSD entails difficulties with social adaptation of the family, leads to severe psychological disorders in the child and his relatives. Sex of a child with DSD should be established only after a full examination and consultation of specialists in this field. A clinical case is presented to illustrate the complexity of differential diagnosis and choice of passport sex in a child with one of the rare forms of DSD.

Fish oil supplementation protects against protein undernutrition-induced testicular and ovarian biochemical alterations in rats

Proteins are required for biological functions and their inadequacy might impair the growth and development of the reproductive system. The study investigated the effects of fish oil (FO) supplementation on low-protein diet-induced alterations in male and female reproductive organs. Male and female rats were assigned randomly to four groups respectively. The NPD rats had five rats per group and were given 16% casein diet while the LPD rats had eight rats per group and received 5% casein diet. After the 8th week, FO was administered for 3 weeks via oral gavage at a concentration of 400 mg Kg−1 after which the rats were sacrificed and testes and ovaries were excised. LPD-fed rats showed lower body weights for both genders. In LPD-fed rats, NO was significantly increased while GSH, vitamins C and E levels, the activities of CAT (except in ovaries), and GST were significantly reduced in both tissues. The activities of SOD and GPx were only reduced in the testes including sperm count, motility, and increase deformed sperm cells. Testosterone and progesterone levels were also reduced and lipid homeostasis was disrupted in the plasma of LPD-fed rats. FO supplementation reduces the NO, CHOL, TG, LDL (in females), and VLDL but significantly improves HDL (in females), testosterone, and progesterone levels, sperm count, motility, and morphology. The antioxidant status of both tissues also increased significantly in LPD-fed rats. Conclusively, FO might be effective in improving testicular and ovarian functions and for the maintenance of plasma lipid homeostasis in LPD-fed rats.

Cocktails of NSAIDs and 17α Ethinylestradiol at Environmentally Relevant Doses in Drinking Water Alter Puberty Onset in Mice Intergenerationally

Non-steroidal anti-inflammatory drugs (NSAIDs) and 17α-ethinyl-estradiol (EE2) are among the most relevant endocrine-disrupting pharmaceuticals found in the environment, particularly in surface and drinking water due to their incomplete removal via wastewater treatment plants. Exposure of pregnant mice to NSAID therapeutic doses during the sex determination period has a negative impact on gonadal development and fertility in adults; however, the effects of their chronic exposure at lower doses are unknown. In this study, we investigated the impact of chronic exposure to a mixture containing ibuprofen, 2hydroxy-ibuprofen, diclofenac, and EE2 at two environmentally relevant doses (added to the drinking water from fetal life until puberty) on the reproductive tract in F1 exposed mice and their F2 offspring. In F1 animals, exposure delayed male puberty and accelerated female puberty. In post-pubertal F1 testes and ovaries, differentiation/maturation of the different gonad cell types was altered, and some of these modifications were observed also in the non-exposed F2 generation. Transcriptomic analysis of post-pubertal testes and ovaries of F1 (exposed) and F2 animals revealed significant changes in gene expression profiles and enriched pathways, particularly the inflammasome, metabolism and extracellular matrix pathways, compared with controls (non-exposed). This suggested that exposure to these drug cocktails has an intergenerational impact. The identified Adverse Outcome Pathway (AOP) networks for NSAIDs and EE2, at doses that are relevant to everyday human exposure, will improve the AOP network of the human reproductive system development concerning endocrine disruptor chemicals. It may serve to identify other putative endocrine disruptors for mammalian species based on the expression of biomarkers.

Gestational exposure to continuous light impairs the development of the female reproductive system in adult Wistar rat offspring.

It has been suggested that maternal exposure to constant light during the gestational period could be considered as a chronic stressor, impairing offspring development by interfering in neuroendocrine and behavior responses. This study aimed to evaluate whether maternal exposure to continuous light during pregnancy affects the adult reproductive system in the female offspring. Pregnant Wistar rats were allocated into light-dark (LD) group, exposed to light and dark photoperiod during gestation, and the light-light (LL) group, exposed to a photoperiod of constant light during gestation. After birth, pups were maintained under normal light-dark photoperiod until adulthood. At postnatal day 90, blood was collected from the female offspring, to analyze plasma luteinizing hormone (LH) and progesterone levels, and the uterus and ovaries were harvested for morphometric, histological, and oxidative stress evaluations. Female exposure to continuous light during the intrauterine period resulted in the adult reduction of LH and increased progesterone plasma levels, and uterine injuries a higher number of endometrial glands and reduced levels of antioxidant enzymes, such as glutathione reductase and glutathione S-transferase. In these experimental conditions, gestational continuous light exposure disturbs sex hormone balance and reduces the antioxidant enzymatic activity in the uterus of female offspring in adult life.

Acrylamide-induced meiotic arrest of spermatocytes in adolescent mice by triggering excessive DNA strand breaks: Potential therapeutic effects of resveratrol.

Background: Baked carbohydrate-rich foods are the main source of acrylamide (AA) in the general population and are widely consumed by teenagers. Considering the crucial development of the reproductive system during puberty, the health risks posed by AA in adolescent males have raised public concern.Methods: In this study, we exposed 3-week-old male pubertal mice to AA for 4weeks to evaluate its effect on spermatogenesis using computer-assisted sperm analysis (CASA) and historical analysis. Flow cytometric analysis and meiocyte spreading assay were conducted to assess meiosis in mice. The expression of meiosis-related proteins and double-strand break (DSB) proteins were evaluated by immunoblot analyses. Additionally, isolated spermatocytes were used to explore the role of resveratrol in AA-induced damages of meiosis.Results: Our results showed that AA decreased the testicular and epididymal indexes, reduced sperm count and motility, and induced morphological disruption of the testes in pubertal mice. Subsequent meiotic analysis revealed that AA increased the proportion of 4C spermatocytes and decreased the proportion of 1C spermatids. The expression levels of meiosis-related proteins (SYCP3, Cyclin A1 and CDK2) were downregulated, and signaling proteins (γH2AX, p-CHK2 and p-ATM) expression levels were upregulated in AA-treated mice testes. Similar expression patterns were observed in primary spermatocytes treated with AA and these effects were reversed significantly by resveratrol.Conclusions: Our results indicate that AA induces meiotic arrest via persistent activation of DSBs, which may contribute to AA-compromised spermatogenesis. Resveratrol could serve as a potential therapeutic agent against AA-induced meiotic toxicity. These data highlight the importance of natural product supplementation for treating AA-related reproductive toxicity.

Morphological and Morphometric Parameters of the Reproductive Organs of Euschistus heros (Hemiptera: Pentatomidae) Treated With a Sublethal Juvenile Hormone Analog

The stinkbug Euschistus heros is an important pest of Brazilian agricultural production with increasing importance in the Neotropical region. High reproductive potential and increased risk of resistance to insecticides are determining factors influencing its pest status. This work evaluated the effects of pyriproxyfen on the reproduction and morphological development of the reproductive system of E. heros. Pyriproxyfen was utilized at sublethal concentrations (LC30) in fourth-instar nymphs (N4). Sublethal pyriproxyfen resulted in a reduction in fertility and fecundity of 2 and 12% when only the males were treated, 47 and 53% when only the females were treated, and 32 and 46% when females and males were treated. Basal oocytes were larger and more previtellogenic in newly emerged pyriproxyfen-treated females. The nuclear area of testicular accessory cells shrunk after 10 and 15 days of age in treated insects. Similarly, testicular shape was altered, changing from an ellipsoid to an obpyriform pattern, characterized by hypertrophy of the basal region over time. The apparent area of the organ grew until ten days of age, then shrunk at 15 days of age. In summary, pyriproxyfen treatments disrupted the normal development of N4 of E. heros and diminished the reproductive potential of female and male adults.

Functions of Steroid Hormones in the Male Reproductive Tract as Revealed by Mouse Models.

Steroid hormones are capable of diffusing through cell membranes to bind with intracellular receptors to regulate numerous physiological processes. Three classes of steroid hormones, namely androgens, estrogens and glucocorticoids, contribute to the development of the reproductive system and the maintenance of fertility. During the past 30 years, mouse models have been produced in which the expression of genes encoding steroid hormone receptors has been enhanced, partially compromised or eliminated. These mouse models have revealed many of the physiological processes regulated by androgens, estrogens and to a more limited extent glucocorticoids in the testis and male accessory organs. In this review, advances provided by mouse models that have facilitated a better understanding of the molecular regulation of testis and reproductive tract processes by steroid hormones are discussed.

Sonographic imaging and differential diagnosis of fetal perineal masses.

This case series describes our experience with a prenatal diagnosis of fetal perineal masses. We propose a clinical-sonographic approach for prenatal workup in cases presenting perineal findings based on imaging the target sign at the posterior perineal triangle, the fetal genitalia, and sacrum. Targeted, structured prenatal anatomical scan in fetuses presenting with perineal masses may aid in the prenatal differential diagnosis and enable appropriate genetic analysis, prenatal counseling, and postnatal treatment.

Cytological and Molecular Mechanism of Low Pollen Grain Viability in a Germplasm Line of Double Lotus

Self-fertilization rate is an essential index of lotus reproductive system development, and pollen activity is a key factor affecting lotus seed setting rate. Based on cytology and molecular biology, this study addresses the main reasons for the low self-set rate of double lotus. It takes two different double lotus breeds into consideration, namely 'Sijingganshan' with a low self-crossing rate and 'Jinfurong' with a high self-crossing rate. Cytological analysis results showed that the pollen abortion caused by excessive degradation of tapetum during the single phase was the root cause for the low self-mating rate of double lotus. Subsequent transcriptome analysis revealed that the gene NnPTC1 related to programmed tapetum cell death was significantly differentially expressed during the critical period of abortion, which further verified the specific expression of NnPTC1 in anthers. It was found that the expression level of NnPTC1 in 'Sijingganshan' at the mononuclear stage of its microspore development was significantly higher than that of 'Jinfurong' at the same stage. The overexpression of NnPTC1 resulted in the premature degradation of the tapetum and significantly decreased seed setting rate. These results indicated that the NnPTC1 gene regulated the pollen abortion of double lotus. The mechanism causing a low seed setting rate for double lotus was preliminarily revealed, which provided a theoretical basis for cultivating lotus varieties with both flower and seed.

Phytocannabinoids, the Endocannabinoid System and Male Reproduction

The endocannabinoid system (ECS) is comprised of a set of lipid-derived messengers (the endocannabinoids, ECBs), proteins that control their production and degradation, and cell-surface cannabinoid (CB) receptors that transduce their actions. ECB molecules such as 2-arachidonoyl-sn-glycerol (2-AG) and anandamide (arachidonoyl ethanolamide) are produced on demand and deactivated through enzymatic actions tightly regulated both temporally and spatially, serving homeostatic roles in order to respond to various challenges to the body. Key components of the ECS are present in the hypothalamus-pituitary-gonadal (HPG) axis, which plays critical roles in the development and regulation of the reproductive system in both males and females. ECB signaling controls the action at each stage of the HPG axis through CB receptors expressed in the hypothalamus, pituitary, and reproductive organs such as the testis and ovary. It regulates the secretion of hypothalamic gonadotropin-releasing hormone (GnRH), pituitary follicle-stimulating hormone (FSH) and luteinizing hormone (LH), estrogen, testosterone, and affects spermatogenesis in males. Δ9-tetrahydrocannabinol (THC) and other phytocannabinoids from Cannabis sativa affect a variety of physiological processes by altering, or under certain conditions hijacking, the ECB system. Therefore, phytocannabinoids, in particular THC, may modify the homeostasis of the HPG axis by altering CB receptor signaling and cause deficits in reproductive function. While the ability of phytocannabinoids, THC and/or cannabidiol (CBD), to reduce pain and inflammation provides promising opportunities for therapeutic intervention for genitourinary and degenerative disorders, important questions remain regarding their unwanted long-term effects. It is nevertheless clear that the therapeutic potential of modulating the ECS calls for further scientific and clinical investigation.

The Effects of Dietary Wheat and Corn Glutens on the Histopathological and Immunohistochemical Structure of the Ovarian Tissue and Serum and Ovarian Tissue LH and FSH Levels and Lipid Profiles in Rats

HIGHLIGHTS The cereals are a significant food source for both humans and animals. The balanced nutrition is critical to the development of the reproductive system. The serum lipid profile is critical to the development of multiple diseases. Dietary gluten has effects on the immunohistochemical structure of the ovarian tissue.

Level of Estrogen in Females-The Different Impacts at Different Life Stages.

Historically, a high level of estrogen in women is regarded as the signature for a longer lifespan than men. Estrogen is known to be responsible for the development and regulation of the female reproductive system and secondary sex characteristics. Ovariectomy brings on numerous complications such as early menopause, heart disease, and osteoporosis. Thus, ovariectomy impacts the long-term health and lifespan of women. However, the level of estrogen at different life stages should be managed differently. Life quality can be measured in many ways, but mainly it relates to how an individual is doing in terms of being healthy, comfortable, and able to participate in or enjoy life experiences. First of all, ovariectomy not only reduces the level of estrogen but also destroys the reproductive metabolism and potentially other metabolism functions; it may also reduce the lifespan because of the overall impact, not necessary due to the low level of estrogen. Secondly, according to the principal law of the lifespan (PLOSP), the impacts of ovariectomy at different life stages will be different. The objective of this article is to provide readers with a new view of the research on estrogen. Based on the PLOSP, we recapture the estrogen levels at different life stages and explore potential alternative approaches to the manipulation of the levels of estrogen based on the biological features of the difference life stages. Thus, a low level of estrogen in the early life stage may make a woman live longer than a woman with a normal level of estrogen. However, a low estrogen level does not equal ovariectomy. Here, we explain the different impacts of the estrogen levels during different life stages; the effects on the lifespan of the manipulation of estrogen levels at different life stages; and the differences among the estrogen levels, ovariectomy effects, life stages, and lifespan. The personalized manipulation of estrogen levels and relevant growth factors according to the characterization of the life stages may be able to extend the heathy lifespan of women.

Chemical constituents from Neopestalotiopsis clavispora culture medium with estrogenic effects in MCF-7 cells

Estrogen is a vital hormone responsible for the development of the female reproductive system. Hence, estrogen deficiency in menopause increases various symptoms. This study aimed to discover biologically active compounds from an EtOAc-extract of Neopestalotiopsis clavispora culture medium which has previously shown estrogenic activity. A new α-pyrone (1) and a new tetramic acid derivative (2), together with hymenosetin (3) and pestalotiollide B (4), were isolated from the extract. The chemical structures of the new compounds were elucidated using MS and NMR spectroscopy, and the absolute configurations were established by quantum mechanical calculations of electronic circular dichroism and gauge-including atomic orbital NMR chemical shift, followed by DP4 + analysis. The isolated compounds were initially tested for their estrogenic activities using MCF-7 estrogen responsive human breast cancer cells. Hymenosetin (3) showed estrogenic activity by increasing the proliferation of MCF-7 cells at the concentration of 2.5 μM via the phosphorylation of estrogen receptor-α.

Antheraea peptide and its analog: Their influence on the maturation of the reproductive system, embryogenesis, and early larval development in Tenebrio molitor L. beetle.

In recent years, many new immunologically active peptides from insects have been identified. Unfortunately, in most cases, their physiological functions are not fully known. One example is yamamarin, a pentapeptide isolated from the caterpillars of the Antheraea yamamai moth. This peptide has strong antiproliferative properties and is probably involved in the regulation of diapause. Additionally, antiviral activity was discovered. The results of the research presented in this paper are, to our knowledge, the first attempt to characterize the biological effects of yamamarin on the functioning of the reproductive processes and embryonic development of insects using a model species, the beetle Tenebrio molitor, a commonly known pest of grain storage. Simultaneously, we tested the possible activity of the molecule in an in vivo system. In this research, we present the multifaceted effects of yamamarin in this beetle. We show that yamamarin influences ovarian growth and development, maturation of terminal oocytes, level of vitellogenin gene transcript, the number of laid eggs, duration of embryonic development, and larval hatching. In experiments with palmitic acid-conjugated yamamarin (C16-yamamarin), we also showed that this peptide is a useful starting molecule for the synthesis of biopharmaceuticals or new peptidomimetics with gonadotropic activity and effects on embryonic development. The data obtained additionally provide new knowledge about the possible function of yamamarin in insect physiology, pointing to the important role of this pentapeptide as a regulator of reproductive processes and embryonic development in a heterologous bioassay with T. molitor.

Distribution of cytoskeletal proteins in the cat testis during the pre-pubertal and post-pubertal periods

Cytoskeletal proteins not only define the shape of cells, but also have critical roles in their proliferation, migration and motility, as well as in the establishment and maintenance of tissue organization and integrity. Furthermore, these proteins influence the physiological processes of the male reproductive system and are found in the structure of some cells. This study aimed to determine differences between the pre- and post-pubertal periods for the localization and distribution of actin, desmin, vimentin and cytokeratin-18 in the testes, epididymides and ductus deferentes of Persian and Turkish Angora and Van cats, using immunohistochemistry. The study material was grouped as belonging to the pre-pubertal and post-pubertal periods. The tissue samples of both groups were subjected to routine histological processing and embedded in paraffin. Serial sections cut from the paraffin-embedded tissue blocks were immunohistochemically stained with the indirect streptavidin-biotin complex method. Immunohistochemical findings demonstrated that there was no difference between the pre- and post-pubertal periods for the staining intensity and distribution of the proteins actin, vimentin, desmin and cytokeratin-18 in Persian and Turkish Angora and Van cats. On the other hand, differences were detected between the pre- and post-pubertal periods for the cellular expression and localization of these proteins in the testes, epididymides and ductus deferentes. Thus, the study results suggest that, based on the expression of actin, desmin, vimentin and cytokeratin-18 in the testes, epididymides and ductus deferentes during both periods, these molecular factors could have a contributory role in the development of the male reproductive system and the regulation of its physiological processes.

Exposure to Low Zearalenone Doses and Changes in the Homeostasis and Concentrations of Endogenous Hormones in Selected Steroid-Sensitive Tissues in Pre-Pubertal Gilts.

This study was undertaken to analyze whether prolonged exposure to low-dose zearalenone (ZEN) mycotoxicosis affects the concentrations of ZEN, α-zearalenol (α-ZEL), and β-zearalenol (β-ZEL) in selected reproductive system tissues (ovaries, uterine horn-ovarian and uterine sections, and the middle part of the cervix), the hypothalamus, and pituitary gland, or the concentrations of selected steroid hormones in pre-pubertal gilts. For 42 days, gilts were administered per os different ZEN doses (MABEL dose [5 µg/kg BW], the highest NOAEL dose [10 µg/kg BW], and the lowest LOAEL dose [15 µg/kg BW]). Tissue samples were collected on days seven, twenty-one, and forty-two of exposure to ZEN (exposure days D1, D2, and D3, respectively). Blood for the analyses of estradiol and progesterone concentrations was collected in vivo on six dates at seven-day intervals (on analytical dates D1-D6). The analyses revealed that both ZEN and its metabolites were accumulated in the examined tissues. On successive analytical dates, the rate of mycotoxin accumulation in the studied tissues decreased gradually by 50% and proportionally to the administered ZEN dose. A hierarchical visualization revealed that values of the carry-over factor (CF) were highest on exposure day D2. In most groups and on most exposure days, the highest CF values were found in the middle part of the cervix, followed by the ovaries, both sections of the uterine horn, and the hypothalamus. These results suggest that ZEN, α-ZEL, and β-ZEL were deposited in all analyzed tissues despite exposure to very low ZEN doses. The presence of these undesirable compounds in the examined tissues can inhibit the somatic development of the reproductive system and compromise neuroendocrine coordination of reproductive competence in pre-pubertal gilts.

Pathogenicity evaluation of GVI-1 lineage infectious bronchitis virus and its long-term effects on reproductive system development in SPF hens.

Infectious bronchitis virus (IBV) has gained increasing attention in the poultry industry due to its ability to cause tissue injuries not only in the respiratory system and kidney but also in the reproductive system of layers. Recently, the GVI-1 lineage IBVs have spread widely in China, whereas their pathogenicity in egg-laying chickens has rarely been studied, especially its long-term influence in egg production upon the early infection in chicks. In this study, 10-day-old SPF chicks were infected with the GVI-1 lineage JX181 strain and monitored over a 170-day period after infection. The pathogenicity evaluation of the JX181 strain included clinical observations, immunohistochemical assay, viral load, viral shedding, gross autopsy, and laying rate. The results showed that JX181 has a high pathogenicity, causing severe system lesions, and the decrease in egg production. In summary, this study describes the long-term damages caused by the early infection with the IBV GVI-1 lineage on the reproductive system of hens, providing a comprehensive understanding of the pathogenicity of the IBV GVI-1 lineage and emphasizing the importance of its early prevention.

PDGF-AA activates AKT and ERK signaling for testicular interstitial Leydig cell growth via primary cilia.

Testes control the development of male reproductive system. The testicular interstitial Leydig cells (Leydig cells) synthesize testosterone for promoting spermatogenesis and secondary sexual characteristics. Type A platelet-derived growth factor (PDGF-AA) is one of the most important growth factors in regulating Leydig cell growth and function. Knockout of PDGF-AA or its congenital receptor PDGFR-α leads to poor testicular development caused by reducing Leydig cell numbers, supporting PDGF-AA/PDGFR-α signaling regulates Leydig cell development. Primary cilium is a cellular antenna that functions as an integrative platform to transduce extracellular signaling for proper development and differentiation. Several receptors including PDGFR-α are observed on primary cilia for initiating signaling cascades in distinct cell types. Here we showed that PDGF-AA/PDGFR-α signaling promoted Leydig cells growth, migration, and invasion via primary cilia. Upon PDGF-AA treatment, AKT and ERK signaling were activated to regulate these cellular events. Interestingly, active AKT and ERK were detected around the base of primary cilia. Depletion of ciliary genes (IFT88 and CEP164) alleviated PDGF-AA-activated AKT and ERK, thus reducing Leydig cell growth, migration, and invasion. Thus, our study not only reveals the function of PDGF-AA/PDGFR-α signaling in maintaining testicular physiology but also uncovers the role of primary cilium and downstream signaling in regulating Leydig cell development.