Background： Upon binding luteinizing hormone in the ovary, the luteinizing hormone/choriogonadotropin receptor （LHCGR） is necessary for follicular maturation and ovulation, as well as luteal function. We detected m...Background： Upon binding luteinizing hormone in the ovary, the luteinizing hormone/choriogonadotropin receptor （LHCGR） is necessary for follicular maturation and ovulation, as well as luteal function. We detected mutations in the LHCGR gene and evaluated their association with superovulation. Methods： Using polymerase chain reaction-single strand sequencing, we examined polymorphisms in LHCGR and Chinese Holstein heifers. conformation polymorphism （PCR-SSCP） and DNA the genotypes associated with superovulation traits in 127 Results： A G/T polymorphism （ss52050737） in exon 11 was significantly associated with the total number of ova and the number of transferable embryos. Conclusions： LHCGR may be a new predictor for superovulation in Chinese Holstein heifers.展开更多
Polycystic ovary syndrome(PCOS)is a heterogeneous disorder with evidence of polygenetic components,and obesity may be a risk factor for hyperandrogen ism.Previous studies have shown that LHCGR is en riched in the ovar...Polycystic ovary syndrome(PCOS)is a heterogeneous disorder with evidence of polygenetic components,and obesity may be a risk factor for hyperandrogen ism.Previous studies have shown that LHCGR is en riched in the ovary and LHCGR deficiency causes infertility without typical PCOS phenotypes.ALMS1 is implicated in obesity and hyperandrogenism,the common phenotypes among PCOS patients.Through whole-exome sequencing of 22 PCOS families and targeted candidate gene sequencing of additional 65 sporadic PCOS patients,we identified potential causative mutations in LHCGR and ALMS1 in a sibling-pair PCOS family and three sporadic PCOS patients.The expression of LHCGRL638 P in granulosa-like tumor cell line(KGN)cells promoted cyclic adenosine monophosphate production and granulosa cell proliferation,indicating that LHCGRL638 P is an activating mutation.Lhcgr~(L642 P/L642 P)mice showed an irregular estrous cycle,reduced follicles with dynamic folliculogenesis,and increased testosterone(T),estradiol(E2),and dehydroepiandrosterone.Lhcgr~(+/L642 P)AIms1~(+/PB)mice displayed increased T and E2 but decreased late secondary and preovulatory follicles.We showed that activating mutation of LHCGR likely plays important roles in the pathophysiology of PCOS involving abnormal reproductive physiology,whereas ALMS1 deficiency may promote anovulatory infertility via elevated androgens,suggesting that the disturbed LHCGR and ALMS1 cooperatively induce PCOS phenotypes,characterized as anovulation and hyperandrogenemia frequently observed in PCOS patients with obesity.展开更多
基金supported by grant #2011BAD19B01,#2011BAD19B03 and #2011BAD19B04 from the National Key Technology R&D program#2011AA100303 from National High-Tech R&D Program
文摘Background： Upon binding luteinizing hormone in the ovary, the luteinizing hormone/choriogonadotropin receptor （LHCGR） is necessary for follicular maturation and ovulation, as well as luteal function. We detected mutations in the LHCGR gene and evaluated their association with superovulation. Methods： Using polymerase chain reaction-single strand sequencing, we examined polymorphisms in LHCGR and Chinese Holstein heifers. conformation polymorphism （PCR-SSCP） and DNA the genotypes associated with superovulation traits in 127 Results： A G/T polymorphism （ss52050737） in exon 11 was significantly associated with the total number of ova and the number of transferable embryos. Conclusions： LHCGR may be a new predictor for superovulation in Chinese Holstein heifers.
基金jointly supported by the National Key Research and Development Program of China(2018YFC1002104 to L.W.,2018YFC1004904 to B.-L.W.and J.F.,2016YFC1000500 to H.Y.W.and W.F.T.)the National Natural Science Foundation of China([81930036,31521003,31771669]to H.Y.W.)+1 种基金the Commission for Science and Technology of Shanghai Municipality(17JC1400902to H.Y.W.)the MDA-CHB Research Grant to B.-L.W。
文摘Polycystic ovary syndrome(PCOS)is a heterogeneous disorder with evidence of polygenetic components,and obesity may be a risk factor for hyperandrogen ism.Previous studies have shown that LHCGR is en riched in the ovary and LHCGR deficiency causes infertility without typical PCOS phenotypes.ALMS1 is implicated in obesity and hyperandrogenism,the common phenotypes among PCOS patients.Through whole-exome sequencing of 22 PCOS families and targeted candidate gene sequencing of additional 65 sporadic PCOS patients,we identified potential causative mutations in LHCGR and ALMS1 in a sibling-pair PCOS family and three sporadic PCOS patients.The expression of LHCGRL638 P in granulosa-like tumor cell line(KGN)cells promoted cyclic adenosine monophosphate production and granulosa cell proliferation,indicating that LHCGRL638 P is an activating mutation.Lhcgr~(L642 P/L642 P)mice showed an irregular estrous cycle,reduced follicles with dynamic folliculogenesis,and increased testosterone(T),estradiol(E2),and dehydroepiandrosterone.Lhcgr~(+/L642 P)AIms1~(+/PB)mice displayed increased T and E2 but decreased late secondary and preovulatory follicles.We showed that activating mutation of LHCGR likely plays important roles in the pathophysiology of PCOS involving abnormal reproductive physiology,whereas ALMS1 deficiency may promote anovulatory infertility via elevated androgens,suggesting that the disturbed LHCGR and ALMS1 cooperatively induce PCOS phenotypes,characterized as anovulation and hyperandrogenemia frequently observed in PCOS patients with obesity.
